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Current Signal Transduction Therapy

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ISSN (Print): 1574-3624
ISSN (Online): 2212-389X

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Review Article

Exploration of Potential Cyclin-dependent Kinases and their Inhibitors to Combat Abnormal Signalling and Cancer

Author(s): Pradeep Pilania, Sisir Nandi, Dinesh Kumar Meena and Brij K. Sharma*

Volume 19, Issue 2, 2024

Published on: 22 February, 2024

Article ID: e220224227336 Pages: 25

DOI: 10.2174/0115743624279638240211170045

Price: $65

Abstract

Regulation of cell proliferation depends on stimulatory and inhibitory factors that act in a coordinated manner in response to external signals. Various agents, including mitogens, growth factors, cytokines, and other external factors, can impact the mitotic cell cycle, resulting in either provoking growth, differentiation, or apoptosis. Many kinases, such as protein kinases, regulate mitotic cell proliferation through normal signalling. One of the major protein kinase family members is cyclin-dependent kinases (CDK), which are responsible for the regulation of cell cycle progression. If the cell cycle-regulatory mechanisms are permanently altered, it can cause abnormal proliferation that leads to neoplasia. This can result in tumour development, where the availability and expression of CDKs become altered, contributing significantly to impaired cell proliferation. Changes like these are often a characteristic of cancer. CDK inhibitors have shown significant clinical benefits in treating various types of tumours in recent years. The output has been achieved by the clinical approvals of particular CDK inhibitors. Researchers have also been studying the proteolysis-targeting chimera (PROTAC) molecule for the last two decades. This molecule uses ubiquitin-mediated proteasome mechanisms to break down specific targets, making it a promising method for targeted protein degradation (TPD). TPD has become a promising therapeutic option for tackling disease-causing proteins that are otherwise challenging to treat using traditional small molecules. This review provides an overview of the state of knowledge and a general understanding of selective or nonselective CDK inhibitors and PROTAC degraders currently under development or clinically approved congeners, focusing on improving cancer therapy.

Graphical Abstract

[1]
Nurse P. A long twentieth century of the cell cycle and beyond. Cell 2000; 100(1): 71-8.
[http://dx.doi.org/10.1016/S0092-8674(00)81684-0] [PMID: 10647932]
[2]
Hanahan D, Weinberg RA. Hallmarks of cancer: The next generation. Cell 2011; 144(5): 646-74.
[http://dx.doi.org/10.1016/j.cell.2011.02.013] [PMID: 21376230]
[3]
Malumbres M. Cyclin-dependent kinases. Genome Biol 2014; 15(6): 122.
[http://dx.doi.org/10.1186/gb4184] [PMID: 25180339]
[4]
Malumbres M, Harlow E, Hunt T, et al. Cyclin-dependent kinases: A family portrait. Nat Cell Biol 2009; 11(11): 1275-6.
[http://dx.doi.org/10.1038/ncb1109-1275] [PMID: 19884882]
[5]
Jeffrey PD, Russo AA, Polyak K, et al. Mechanism of CDK activation revealed by the structure of a cyclinA-CDK2 complex. Nature 1995; 376(6538): 313-20.
[http://dx.doi.org/10.1038/376313a0] [PMID: 7630397]
[6]
Russo AA, Jeffrey PD, Pavletich NP. Structural basis of cyclin-dependent kinase activation by phosphorylation. Nat Struct Mol Biol 1996; 3(8): 696-700.
[http://dx.doi.org/10.1038/nsb0896-696] [PMID: 8756328]
[7]
Mueller PR, Coleman TR, Kumagai A, Dunphy WG. Myt1: A membrane-associated inhibitory kinase that phosphorylates Cdc2 on both threonine-14 and tyrosine-15. Science 1995; 270(5233): 86-90.
[http://dx.doi.org/10.1126/science.270.5233.86] [PMID: 7569953]
[8]
Sherr CJ. Cancer cell cycles. Science 1996; 274(5293): 1672-7.
[http://dx.doi.org/10.1126/science.274.5293.1672] [PMID: 8939849]
[9]
van den Heuvel S, Harlow E. Distinct roles for cyclin-dependent kinases in cell cycle control. Science 1993; 262(5142): 2050-4.
[http://dx.doi.org/10.1126/science.8266103] [PMID: 8266103]
[10]
Aktas H, Cai H, Cooper GM. Ras links growth factor signaling to the cell cycle machinery via regulation of cyclin D1 and the CDK inhibitor p27KIP1. Mol Cell Biol 1997; 17(7): 3850-7.
[http://dx.doi.org/10.1128/MCB.17.7.3850] [PMID: 9199319]
[11]
Marshall C. How do small GTPase signal transduction pathways regulate cell cycle entry? Curr Opin Cell Biol 1999; 11(6): 732-6.
[http://dx.doi.org/10.1016/S0955-0674(99)00044-7] [PMID: 10600705]
[12]
Rodgers JT, King KY, Brett JO, et al. mTORC1 controls the adaptive transition of quiescent stem cells from G0 to GAlert. Nature 2014; 510(7505): 393-6.
[http://dx.doi.org/10.1038/nature13255] [PMID: 24870234]
[13]
Balmanno K, Cook SJ. Sustained MAP kinase activation is required for the expression of cyclin D1, p21Cip1 and a subset of AP-1 proteins in CCL39 cells. Oncogene 1999; 18(20): 3085-97.
[http://dx.doi.org/10.1038/sj.onc.1202647] [PMID: 10340380]
[14]
Lavoie JN, L’Allemain G, Brunet A, Müller R, Pouysségur J. Cyclin D1 expression is regulated positively by the p42/p44MAPK and negatively by the p38/HOGMAPK pathway. J Biol Chem 1996; 271(34): 20608-16.
[http://dx.doi.org/10.1074/jbc.271.34.20608] [PMID: 8702807]
[15]
Peeper DS, Upton TM, Ladha MH, et al. Ras signalling linked to the cell-cycle machinery by the retinoblastoma protein. Nature 1997; 386(6621): 177-81.
[http://dx.doi.org/10.1038/386177a0] [PMID: 9062190]
[16]
Blais A, Dynlacht BD. E2F-associated chromatin modifiers and cell cycle control. Curr Opin Cell Biol 2007; 19(6): 658-62.
[http://dx.doi.org/10.1016/j.ceb.2007.10.003] [PMID: 18023996]
[17]
Zhang HS, Dean DC. Rb-mediated chromatin structure regulation and transcriptional repression. Oncogene 2001; 20(24): 3134-8.
[http://dx.doi.org/10.1038/sj.onc.1204338] [PMID: 11420730]
[18]
Classon M, Harlow E. The retinoblastoma tumour suppressor in development and cancer. Nat Rev Cancer 2002; 2(12): 910-7.
[http://dx.doi.org/10.1038/nrc950] [PMID: 12459729]
[19]
Mittnacht S, Lees JA, Desai D, Harlow E, Morgan DO, Weinberg RA. Distinct sub-populations of the retinoblastoma protein show a distinct pattern of phosphorylation. EMBO J 1994; 13(1): 118-27.
[http://dx.doi.org/10.1002/j.1460-2075.1994.tb06241.x] [PMID: 8306955]
[20]
Zarkowska T, Mittnacht S. Differential phosphorylation of the retinoblastoma protein by G1/S cyclin-dependent kinases. J Biol Chem 1997; 272(19): 12738-46.
[http://dx.doi.org/10.1074/jbc.272.19.12738] [PMID: 9139732]
[21]
Narasimha AM, Kaulich M, Shapiro GS, et al. Cyclin D activates the Rb tumor suppressor by mono-phosphorylation. eLife 2014; 3: e02872.
[http://dx.doi.org/10.7554/eLife.02872] [PMID: 24876129]
[22]
Malumbres M, Barbacid M. Cell cycle, CDKs and cancer: A changing paradigm. Nat Rev Cancer 2009; 9(3): 153-66.
[http://dx.doi.org/10.1038/nrc2602] [PMID: 19238148]
[23]
Anders L, Ke N, Hydbring P, et al. A systematic screen for CDK4/6 substrates links FOXM1 phosphorylation to senescence suppression in cancer cells. Cancer Cell 2011; 20(5): 620-34.
[http://dx.doi.org/10.1016/j.ccr.2011.10.001] [PMID: 22094256]
[24]
Kalinichenko VV, Major ML, Wang X, et al. Foxm1b transcription factor is essential for development of hepatocellular carcinomas and is negatively regulated by the p19 ARF tumor suppressor. Genes Dev 2004; 18(7): 830-50.
[http://dx.doi.org/10.1101/gad.1200704] [PMID: 15082532]
[25]
Liu M, Dai B, Kang SH, et al. FoxM1B is overexpressed in human glioblastomas and critically regulates the tumorigenicity of glioma cells. Cancer Res 2006; 66(7): 3593-602.
[http://dx.doi.org/10.1158/0008-5472.CAN-05-2912] [PMID: 16585184]
[26]
Wang IC, Chen YJ, Hughes D, et al. Forkhead box M1 regulates the transcriptional network of genes essential for mitotic progression and genes encoding the SCF (Skp2-Cks1) ubiquitin ligase. Mol Cell Biol 2005; 25(24): 10875-94.
[http://dx.doi.org/10.1128/MCB.25.24.10875-10894.2005] [PMID: 16314512]
[27]
Wang IC, Chen YJ, Hughes DE, et al. FoxM1 regulates transcription of JNK1 to promote the G1/S transition and tumor cell invasiveness. J Biol Chem 2008; 283(30): 20770-8.
[http://dx.doi.org/10.1074/jbc.M709892200] [PMID: 18524773]
[28]
Rane SG, Dubus P, Mettus RV, et al. Loss of CDK4 expression causes insulin-deficient diabetes and CDK4 activation results in β-islet cell hyperplasia. Nat Genet 1999; 22(1): 44-52.
[http://dx.doi.org/10.1038/8751] [PMID: 10319860]
[29]
Tsutsui T, Hesabi B, Moons DS, et al. Targeted disruption of CDK4 delays cell cycle entry with enhanced p27(Kip1) activity. Mol Cell Biol 1999; 19(10): 7011-9.
[http://dx.doi.org/10.1128/MCB.19.10.7011] [PMID: 10490638]
[30]
Malumbres M, Sotillo R, Santamaría D, et al. Mammalian cells cycle without the D-type cyclin-dependent kinases CDK4 and CDK6. Cell 2004; 118(4): 493-504.
[http://dx.doi.org/10.1016/j.cell.2004.08.002] [PMID: 15315761]
[31]
Kozar K, Ciemerych MA, Rebel VI, et al. Mouse development and cell proliferation in the absence of D-cyclins. Cell 2004; 118(4): 477-91.
[http://dx.doi.org/10.1016/j.cell.2004.07.025] [PMID: 15315760]
[32]
Barrière C, Santamaría D, Cerqueira A, et al. Mice thrive without CDK4 and CDK2. Mol Oncol 2007; 1(1): 72-83.
[http://dx.doi.org/10.1016/j.molonc.2007.03.001] [PMID: 19383288]
[33]
Harbour JW, Luo RX, Santi AD, Postigo AA, Dean DC. CDK phosphorylation triggers sequential intramolecular interactions that progressively block Rb functions as cells move through G1. Cell 1999; 98(6): 859-69.
[http://dx.doi.org/10.1016/S0092-8674(00)81519-6] [PMID: 10499802]
[34]
Helin K. Regulation of cell proliferation by the E2F transcription factors. Curr Opin Genet Dev 1998; 8(1): 28-35.
[http://dx.doi.org/10.1016/S0959-437X(98)80058-0] [PMID: 9529602]
[35]
Asghar U, Witkiewicz AK, Turner NC, Knudsen ES. The history and future of targeting cyclin-dependent kinases in cancer therapy. Nat Rev Drug Discov 2015; 14(2): 130-46.
[http://dx.doi.org/10.1038/nrd4504] [PMID: 25633797]
[36]
Ortega S, Prieto I, Odajima J, et al. Cyclin-dependent kinase 2 is essential for meiosis but not for mitotic cell division in mice. Nat Genet 2003; 35(1): 25-31.
[http://dx.doi.org/10.1038/ng1232] [PMID: 12923533]
[37]
Tetsu O, McCormick F. Proliferation of cancer cells despite CDK2 inhibition. Cancer Cell 2003; 3(3): 233-45.
[http://dx.doi.org/10.1016/S1535-6108(03)00053-9] [PMID: 12676582]
[38]
Merrick KA, Wohlbold L, Zhang C, et al. Switching CDK2 on or off with small molecules to reveal requirements in human cell proliferation. Mol Cell 2011; 42(5): 624-36.
[http://dx.doi.org/10.1016/j.molcel.2011.03.031] [PMID: 21658603]
[39]
Gopinathan L, Tan SLW, Padmakumar VC, Coppola V, Tessarollo L, Kaldis P. Loss of CDK2 and cyclin A2 impairs cell proliferation and tumorigenesis. Cancer Res 2014; 74(14): 3870-9.
[http://dx.doi.org/10.1158/0008-5472.CAN-13-3440] [PMID: 24802190]
[40]
Laoukili J, Alvarez M, Meijer LAT, et al. Activation of FoxM1 during G2 requires cyclin A/CDK-dependent relief of autorepression by the FoxM1 N-terminal domain. Mol Cell Biol 2008; 28(9): 3076-87.
[http://dx.doi.org/10.1128/MCB.01710-07] [PMID: 18285455]
[41]
Marais A, Ji Z, Child ES, Krause E, Mann DJ, Sharrocks AD. Cell cycle-dependent regulation of the forkhead transcription factor FOXK2 by CDK•cyclin complexes. J Biol Chem 2010; 285(46): 35728-39.
[http://dx.doi.org/10.1074/jbc.M110.154005] [PMID: 20810654]
[42]
Sadasivam S, Duan S, DeCaprio JA. The MuvB complex sequentially recruits B-Myb and FoxM1 to promote mitotic gene expression. Genes Dev 2012; 26(5): 474-89.
[http://dx.doi.org/10.1101/gad.181933.111] [PMID: 22391450]
[43]
Peter M, Nakagawa J, Dorée M, Labbé JC, Nigg EA. Identification of major nucleolar proteins as candidate mitotic substrates of cdc2 kinase. Cell 1990; 60(5): 791-801.
[http://dx.doi.org/10.1016/0092-8674(90)90093-T] [PMID: 2178776]
[44]
Peter M, Nakagawa J, Dorée M, Labbé JC, Nigg EA. In vitro disassembly of the nuclear lamina and M phase-specific phosphorylation of lamins by cdc2 kinase. Cell 1990; 61(4): 591-602.
[http://dx.doi.org/10.1016/0092-8674(90)90471-P] [PMID: 2188731]
[45]
Belenguer P, Caizergues-Ferrer M, Labbé JC, Dorée M, Amalric F. Mitosis-specific phosphorylation of nucleolin by p34cdc2 protein kinase. Mol Cell Biol 1990; 10(7): 3607-18.
[http://dx.doi.org/10.1128/mcb.10.7.3607-3618.1990] [PMID: 2192260]
[46]
Johnson N, Cai D, Kennedy RD, et al. CDK1 participates in BRCA1-dependent S phase checkpoint control in response to DNA damage. Mol Cell 2009; 35(3): 327-39.
[http://dx.doi.org/10.1016/j.molcel.2009.06.036] [PMID: 19683496]
[47]
Johnson N, Li YC, Walton ZE, et al. Compromised CDK1 activity sensitizes BRCA-proficient cancers to PARP inhibition. Nat Med 2011; 17(7): 875-82.
[http://dx.doi.org/10.1038/nm.2377] [PMID: 21706030]
[48]
Santamaría D, Barrière C, Cerqueira A, et al. CDK1 is sufficient to drive the mammalian cell cycle. Nature 2007; 448(7155): 811-5.
[http://dx.doi.org/10.1038/nature06046] [PMID: 17700700]
[49]
Brandeis M, Rosewell I, Carrington M, et al. Cyclin B2-null mice develop normally and are fertile whereas cyclin B1-null mice die in utero. Proc Natl Acad Sci 1998; 95(8): 4344-9.
[http://dx.doi.org/10.1073/pnas.95.8.4344] [PMID: 9539739]
[50]
Murphy M, Stinnakre MG, Senamaud-Beaufort C, et al. Delayed early embryonic lethality following disruption of the murine cyclin A2 gene. Nat Genet 1997; 15(1): 83-6.
[http://dx.doi.org/10.1038/ng0197-83] [PMID: 8988174]
[51]
Li B, Carey M, Workman JL. The role of chromatin during transcription. Cell 2007; 128(4): 707-19.
[http://dx.doi.org/10.1016/j.cell.2007.01.015] [PMID: 17320508]
[52]
Corden JL. RNA polymerase II C-terminal domain: Tethering transcription to transcript and template. Chem Rev 2013; 113(11): 8423-55.
[http://dx.doi.org/10.1021/cr400158h] [PMID: 24040939]
[53]
Eick D, Geyer M. The RNA polymerase II carboxy-terminal domain (CTD) code. Chem Rev 2013; 113(11): 8456-90.
[http://dx.doi.org/10.1021/cr400071f] [PMID: 23952966]
[54]
Fisher RP. The CDK Network: Linking cycles of cell division and gene expression. Genes Cancer 2012; 3(11-12): 731-8.
[http://dx.doi.org/10.1177/1947601912473308] [PMID: 23634260]
[55]
Jasnovidova O, Stefl R. The CTD code of RNA polymerase II: A structural view. Wiley Interdiscip Rev RNA 2013; 4(1): 1-16.
[http://dx.doi.org/10.1002/wrna.1138] [PMID: 23042580]
[56]
Jeronimo C, Bataille AR, Robert F. The writers, readers, and functions of the RNA polymerase II C-terminal domain code. Chem Rev 2013; 113(11): 8491-522.
[http://dx.doi.org/10.1021/cr4001397] [PMID: 23837720]
[57]
Jeronimo C, Collin P, Robert F. The RNA polymerase II CTD: The increasing complexity of a low-complexity protein domain. J Mol Biol 2016; 428(12): 2607-22.
[http://dx.doi.org/10.1016/j.jmb.2016.02.006] [PMID: 26876604]
[58]
Bataille AR, Jeronimo C, Jacques PÉ, et al. A universal RNA polymerase II CTD cycle is orchestrated by complex interplays between kinase, phosphatase, and isomerase enzymes along genes. Mol Cell 2012; 45(2): 158-70.
[http://dx.doi.org/10.1016/j.molcel.2011.11.024] [PMID: 22284676]
[59]
Drogat J, Hermand D. Gene‐specific requirement of RNA polymerase II CTD phosphorylation. Mol Microbiol 2012; 84(6): 995-1004.
[http://dx.doi.org/10.1111/j.1365-2958.2012.08071.x] [PMID: 22553990]
[60]
Mayer A, Lidschreiber M, Siebert M, Leike K, Söding J, Cramer P. Uniform transitions of the general RNA polymerase II transcription complex. Nat Struct Mol Biol 2010; 17(10): 1272-8.
[http://dx.doi.org/10.1038/nsmb.1903] [PMID: 20818391]
[61]
Gupta K, Sari-Ak D, Haffke M, Trowitzsch S, Berger I. Zooming in on transcription preinitiation. J Mol Biol 2016; 428(12): 2581-91.
[http://dx.doi.org/10.1016/j.jmb.2016.04.003] [PMID: 27067110]
[62]
Ganuza M, Sáiz-Ladera C, Cañamero M, et al. Genetic inactivation of CDK7 leads to cell cycle arrest and induces premature aging due to adult stem cell exhaustion. EMBO J 2012; 31(11): 2498-510.
[http://dx.doi.org/10.1038/emboj.2012.94] [PMID: 22505032]
[63]
Rossi DJ, Londesborough A, Korsisaari N, et al. Inability to enter S phase and defective RNA polymerase II CTD phosphorylation in mice lacking Mat1. EMBO J 2001; 20(11): 2844-56.
[http://dx.doi.org/10.1093/emboj/20.11.2844] [PMID: 11387217]
[64]
Patel H, Abduljabbar R, Lai CF, et al. Expression of CDK7, Cyclin H, and MAT1 is elevated in breast cancer and is prognostic in estrogen receptor–positive breast cancer. Clin Cancer Res 2016; 22(23): 5929-38.
[http://dx.doi.org/10.1158/1078-0432.CCR-15-1104] [PMID: 27301701]
[65]
Wang Y, Zhang T, Kwiatkowski N, et al. CDK7-dependent transcriptional addiction in triple-negative breast cancer. Cell 2015; 163(1): 174-86.
[http://dx.doi.org/10.1016/j.cell.2015.08.063] [PMID: 26406377]
[66]
Larochelle S, Amat R, Glover-Cutter K, et al. Cyclin-dependent kinase control of the initiation-to-elongation switch of RNA polymerase II. Nat Struct Mol Biol 2012; 19(11): 1108-15.
[http://dx.doi.org/10.1038/nsmb.2399] [PMID: 23064645]
[67]
Viladevall L, St Amour CV, Rosebrock A, et al. TFIIH and P-TEFb coordinate transcription with capping enzyme recruitment at specific genes in fission yeast. Mol Cell 2009; 33(6): 738-51.
[http://dx.doi.org/10.1016/j.molcel.2009.01.029] [PMID: 19328067]
[68]
Sonawane YA, Taylor MA, Napoleon JV, Rana S, Contreras JI, Natarajan A. Cyclin dependent kinase 9 inhibitors for cancer therapy. J Med Chem 2016; 59(19): 8667-84.
[http://dx.doi.org/10.1021/acs.jmedchem.6b00150] [PMID: 27171036]
[69]
Devaiah BN, Singer DS. Cross-talk among RNA polymerase II kinases modulates C-terminal domain phosphorylation. J Biol Chem 2012; 287(46): 38755-66.
[http://dx.doi.org/10.1074/jbc.M112.412015] [PMID: 23027873]
[70]
Ramakrishnan R, Rice AP. CDK9 T‐loop phosphorylation is regulated by the calcium signaling pathway. J Cell Physiol 2012; 227(2): 609-17.
[http://dx.doi.org/10.1002/jcp.22760] [PMID: 21448926]
[71]
Bose P, Simmons GL, Grant S. Cyclin-dependent kinase inhibitor therapy for hematologic malignancies. Expert Opin Investig Drugs 2013; 22(6): 723-38.
[http://dx.doi.org/10.1517/13543784.2013.789859] [PMID: 23647051]
[72]
Wang S, Fischer P. Cyclin-dependent kinase 9: A key transcriptional regulator and potential drug target in oncology, virology and cardiology. Trends Pharmacol Sci 2008; 29(6): 302-13.
[http://dx.doi.org/10.1016/j.tips.2008.03.003] [PMID: 18423896]
[73]
Wang S, Griffiths G, Midgley CA, et al. Discovery and characterization of 2-anilino-4- (thiazol-5-yl)pyrimidine transcriptional CDK inhibitors as anticancer agents. Chem Biol 2010; 17(10): 1111-21.
[http://dx.doi.org/10.1016/j.chembiol.2010.07.016] [PMID: 21035734]
[74]
Garriga J, Xie H, Obradovic Z, Graña X. Selective control of gene expression by CDK9 in human cells. J Cell Physiol 2010; 222(1): 200-8.
[http://dx.doi.org/10.1002/jcp.21938] [PMID: 19780058]
[75]
Huang CH, Lujambio A, Zuber J, et al. CDK9-mediated transcription elongation is required for MYC addiction in hepatocellular carcinoma. Genes Dev 2014; 28(16): 1800-14.
[http://dx.doi.org/10.1101/gad.244368.114] [PMID: 25128497]
[76]
Lam F, Abbas AY, Shao H, et al. Targeting RNA transcription and translation in ovarian cancer cells with pharmacological inhibitor CDKI-73. Oncotarget 2014; 5(17): 7691-704.
[http://dx.doi.org/10.18632/oncotarget.2296] [PMID: 25277198]
[77]
Storch K, Cordes N. The impact of CDK9 on radiosensitivity, DNA damage repair and cell cycling of HNSCC cancer cells. Int J Oncol 2016; 48(1): 191-8.
[http://dx.doi.org/10.3892/ijo.2015.3246] [PMID: 26573875]
[78]
Wang Z-Q, Johnson CL, Kumar A, et al. Inhibition of P-TEFb by DRB suppresses SIRT1/CK2α pathway and enhances radiosensitivity of human cancer cells. Anticancer Res 2014; 34(12): 6981-9.
[PMID: 25503124]
[79]
Yang J, Zhao Y, Kalita M, et al. Systematic determination of human cyclin dependent kinase (CDK)-9 interactome identifies novel functions in RNA splicing mediated by the dead box (DDX)-5/17 RNA helicases. Mol Cell Proteomics 2015; 14(10): 2701-21.
[http://dx.doi.org/10.1074/mcp.M115.049221] [PMID: 26209609]
[80]
Bartkowiak B, Greenleaf AL. Phosphorylation of RNAPII. Transcription 2011; 2(3): 115-9.
[http://dx.doi.org/10.4161/trns.2.3.15004] [PMID: 21826281]
[81]
Bartkowiak B, Liu P, Phatnani HP, et al. CDK12 is a transcription elongation-associated CTD kinase, the metazoan ortholog of yeast Ctk1. Genes Dev 2010; 24(20): 2303-16.
[http://dx.doi.org/10.1101/gad.1968210] [PMID: 20952539]
[82]
Bartkowiak B, Yan C, Greenleaf AL. Engineering an analog-sensitive CDK12 cell line using CRISPR/Cas. Biochim Biophys Acta Gene Regul Mech 2015; 1849(9): 1179-87.
[http://dx.doi.org/10.1016/j.bbagrm.2015.07.010] [PMID: 26189575]
[83]
Juan H-C, Lin Y, Chen H-R, Fann M-J. CDK12 is essential for embryonic development and the maintenance of genomic stability. Cell Death Differ 2016; 23(6): 1038-48.
[http://dx.doi.org/10.1038/cdd.2015.157] [PMID: 26658019]
[84]
Blazek D, Kohoutek J, Bartholomeeusen K, et al. The Cyclin K/CDK12 complex maintains genomic stability via regulation of expression of DNA damage response genes. Genes Dev 2011; 25(20): 2158-72.
[http://dx.doi.org/10.1101/gad.16962311] [PMID: 22012619]
[85]
Chen HH, Wang YC, Fann MJ. Identification and characterization of the CDK12/cyclin L1 complex involved in alternative splicing regulation. Mol Cell Biol 2006; 26(7): 2736-45.
[http://dx.doi.org/10.1128/MCB.26.7.2736-2745.2006] [PMID: 16537916]
[86]
Eifler TT, Shao W, Bartholomeeusen K, et al. Cyclin-dependent kinase 12 increases 3′ end processing of growth factor-induced c-FOS transcripts. Mol Cell Biol 2015; 35(2): 468-78.
[http://dx.doi.org/10.1128/MCB.01157-14] [PMID: 25384976]
[87]
Ko TK, Kelly E, Pines J, Crk RS, Crk RS. J Cell Sci 2001; 114(14): 2591-603.
[http://dx.doi.org/10.1242/jcs.114.14.2591] [PMID: 11683387]
[88]
Liang K, Gao X, Gilmore JM, et al. Characterization of human cyclin-dependent kinase 12 (CDK12) and CDK13 complexes in C-terminal domain phosphorylation, gene transcription, and RNA processing. Mol Cell Biol 2015; 35(6): 928-38.
[http://dx.doi.org/10.1128/MCB.01426-14] [PMID: 25561469]
[89]
Davidson L, Muniz L, West S. 3′ end formation of pre-mRNA and phosphorylation of Ser2 on the RNA polymerase II CTD are reciprocally coupled in human cells. Genes Dev 2014; 28(4): 342-56.
[http://dx.doi.org/10.1101/gad.231274.113] [PMID: 24478330]
[90]
Kauraniemi P, Bärlund M, Monni O, Kallioniemi A. New amplified and highly expressed genes discovered in the ERBB2 amplicon in breast cancer by cDNA microarrays. Cancer Res 2001; 61(22): 8235-40.
[PMID: 11719455]
[91]
Kauraniemi P, Kuukasjärvi T, Sauter G, Kallioniemi A. Amplification of a 280-kilobase core region at the ERBB2 locus leads to activation of two hypothetical proteins in breast cancer. Am J Pathol 2003; 163(5): 1979-84.
[http://dx.doi.org/10.1016/S0002-9440(10)63556-0] [PMID: 14578197]
[92]
Joshi PM, Sutor SL, Huntoon CJ, Karnitz LM. Ovarian cancer-associated mutations disable catalytic activity of CDK12, a kinase that promotes homologous recombination repair and resistance to cisplatin and poly(ADP-ribose) polymerase inhibitors. J Biol Chem 2014; 289(13): 9247-53.
[http://dx.doi.org/10.1074/jbc.M114.551143] [PMID: 24554720]
[93]
Bajrami I, Frankum JR, Konde A, et al. Genome-wide profiling of genetic synthetic lethality identifies CDK12 as a novel determinant of PARP1/2 inhibitor sensitivity. Cancer Res 2014; 74(1): 287-97.
[http://dx.doi.org/10.1158/0008-5472.CAN-13-2541] [PMID: 24240700]
[94]
Iorns E, Martens-de Kemp SR, Lord CJ, Ashworth A. CRK7 modifies the MAPK pathway and influences the response to endocrine therapy. Carcinogenesis 2009; 30(10): 1696-701.
[http://dx.doi.org/10.1093/carcin/bgp187] [PMID: 19651820]
[95]
Liu Y, Ranish JA, Aebersold R, Hahn S. Yeast nuclear extract contains two major forms of RNA polymerase II mediator complexes. J Biol Chem 2001; 276(10): 7169-75.
[http://dx.doi.org/10.1074/jbc.M009586200] [PMID: 11383511]
[96]
Taatjes DJ, Näär AM, Andel F III, Nogales E, Tjian R. Structure, function, and activator-induced conformations of the CRSP coactivator. Science 2002; 295(5557): 1058-62.
[http://dx.doi.org/10.1126/science.1065249] [PMID: 11834832]
[97]
Tsai KL, Sato S, Tomomori-Sato C, Conaway RC, Conaway JW, Asturias FJ. A conserved Mediator–CDK8 kinase module association regulates Mediator–RNA polymerase II interaction. Nat Struct Mol Biol 2013; 20(5): 611-9.
[http://dx.doi.org/10.1038/nsmb.2549] [PMID: 23563140]
[98]
Donner AJ, Ebmeier CC, Taatjes DJ, Espinosa JM. CDK8 is a positive regulator of transcriptional elongation within the serum response network. Nat Struct Mol Biol 2010; 17(2): 194-201.
[http://dx.doi.org/10.1038/nsmb.1752] [PMID: 20098423]
[99]
Galbraith MD, Allen MA, Bensard CL, et al. HIF1A employs CDK8-mediator to stimulate RNAPII elongation in response to hypoxia. Cell 2013; 153(6): 1327-39.
[http://dx.doi.org/10.1016/j.cell.2013.04.048] [PMID: 23746844]
[100]
Bancerek J, Poss ZC, Steinparzer I, et al. CDK8 kinase phosphorylates transcription factor STAT1 to selectively regulate the interferon response. Immunity 2013; 38(2): 250-62.
[http://dx.doi.org/10.1016/j.immuni.2012.10.017] [PMID: 23352233]
[101]
Morris EJ, Ji JY, Yang F, et al. E2F1 represses β-catenin transcription and is antagonized by both pRB and CDK8. Nature 2008; 455(7212): 552-6.
[http://dx.doi.org/10.1038/nature07310] [PMID: 18794899]
[102]
Zhao J, Ramos R, Demma M. CDK8 regulates E2F1 transcriptional activity through S375 phosphorylation. Oncogene 2013; 32(30): 3520-30.
[http://dx.doi.org/10.1038/onc.2012.364] [PMID: 22945643]
[103]
Alarcón C, Zaromytidou AI, Xi Q, et al. Nuclear CDKs drive Smad transcriptional activation and turnover in BMP and TGF-β pathways. Cell 2009; 139(4): 757-69.
[http://dx.doi.org/10.1016/j.cell.2009.09.035] [PMID: 19914168]
[104]
Fryer CJ, White JB, Jones KA. Mastermind recruits CycC:CDK8 to phosphorylate the Notch ICD and coordinate activation with turnover. Mol Cell 2004; 16(4): 509-20.
[http://dx.doi.org/10.1016/j.molcel.2004.10.014] [PMID: 15546612]
[105]
Zhao X, Feng D, Wang Q, et al. Regulation of lipogenesis by cyclin-dependent kinase 8–mediated control of SREBP-1. J Clin Invest 2012; 122(7): 2417-27.
[http://dx.doi.org/10.1172/JCI61462] [PMID: 22684109]
[106]
Tsutsui T, Umemura H, Tanaka A, Mizuki F, Hirose Y, Ohkuma Y. Human mediator kinase subunit CDK11 plays a negative role in viral activator VP16‐dependent transcriptional regulation. Genes Cells 2008; 13(8): 817-26.
[http://dx.doi.org/10.1111/j.1365-2443.2008.01208.x] [PMID: 18651850]
[107]
Westerling T, Kuuluvainen E, Maäkelaä TP. CDK8 is essential for preimplantation mouse development. Mol Cell Biol 2007; 27(17): 6177-82.
[http://dx.doi.org/10.1128/MCB.01302-06] [PMID: 17620419]
[108]
McCleland ML, Soukup TM, Liu SD, Esensten JH. CDK8 Deletion in the ApcMinmurinetumour model represses EZH2 activity and accelerates tumourigenesis: CDK8 knockout promotes tumorigenesis in apcmin mice. J Pathol 2015; 237(4): 508-19.
[http://dx.doi.org/10.1002/path.4596] [PMID: 26235356]
[109]
Allen BL, Taatjes DJ. The Mediator complex: A central integrator of transcription. Nat Rev Mol Cell Biol 2015; 16(3): 155-66.
[http://dx.doi.org/10.1038/nrm3951] [PMID: 25693131]
[110]
Mitra AP, Almal AA, George B, et al. The use of genetic programming in the analysis of quantitative gene expression profiles for identification of nodal status in bladder cancer. BMC Cancer 2006; 6(1): 159.
[http://dx.doi.org/10.1186/1471-2407-6-159] [PMID: 16780590]
[111]
Chattopadhyay I, Singh A, Phukan R, et al. Genome-wide analysis of chromosomal alterations in patients with esophageal squamous cell carcinoma exposed to tobacco and betel quid from high-risk area in India. Mutat Res Genet Toxicol Environ Mutagen 2010; 696(2): 130-8.
[http://dx.doi.org/10.1016/j.mrgentox.2010.01.001] [PMID: 20083228]
[112]
Firestein R, Shima K, Nosho K, et al. CDK8 expression in 470 colorectal cancers in relation to β‐catenin activation, other molecular alterations and patient survival. Int J Cancer 2010; 126(12): 2863-73.
[http://dx.doi.org/10.1002/ijc.24908] [PMID: 19790197]
[113]
Lim, Han SI, Lim SC. Role of CDK8 and β-catenin in colorectal adenocarcinoma. Oncol Rep 2010; 24(1): 285-91.
[http://dx.doi.org/10.3892/or_00000858] [PMID: 20514474]
[114]
Adler AS, McCleland ML, Truong T, et al. CDK8 maintains tumor dedifferentiation and embryonic stem cell pluripotency. Cancer Res 2012; 72(8): 2129-39.
[http://dx.doi.org/10.1158/0008-5472.CAN-11-3886] [PMID: 22345154]
[115]
Firestein R, Bass AJ, Kim SY, et al. CDK8 is a colorectal cancer oncogene that regulates β-catenin activity. Nature 2008; 455(7212): 547-51.
[http://dx.doi.org/10.1038/nature07179] [PMID: 18794900]
[116]
Brägelmann J, Klümper N, Offermann A, et al. Pan-cancer analysis of the mediator complex transcriptome identifies CDK19 and CDK8 as therapeutic targets in advanced prostate cancer. Clin Cancer Res 2017; 23(7): 1829-40.
[http://dx.doi.org/10.1158/1078-0432.CCR-16-0094] [PMID: 27678455]
[117]
Lim, Han SI, Lim SC. Roles of cyclin-dependent kinase 8 and β-catenin in the oncogenesis and progression of gastric adenocarcinoma. Int J Oncol 2011; 38(5): 1375-83.
[http://dx.doi.org/10.3892/ijo.2011.948] [PMID: 21344156]
[118]
Carrera I, Janody F, Leeds N, Duveau F, Treisman JE. Pygopus activates Wingless target gene transcription through the mediator complex subunits Med12 and Med13. Proc Natl Acad Sci 2008; 105(18): 6644-9.
[http://dx.doi.org/10.1073/pnas.0709749105] [PMID: 18451032]
[119]
Kim S, Xu X, Hecht A, Boyer TG. Mediator is a transducer of Wnt/β-catenin signaling. J Biol Chem 2006; 281(20): 14066-75.
[http://dx.doi.org/10.1074/jbc.M602696200] [PMID: 16565090]
[120]
Rocha PP, Scholze M, Bleiß W, Schrewe H. Med12 is essential for early mouse development and for canonical Wnt and Wnt/PCP signaling. Development 2010; 137(16): 2723-31.
[http://dx.doi.org/10.1242/dev.053660] [PMID: 20630950]
[121]
Bagella L, Giacinti C, Simone C, Giordano A. Identification of murine CDK10: Association with Ets2 transcription factor and effects on the cell cycle. J Cell Biochem 2006; 99(3): 978-85.
[http://dx.doi.org/10.1002/jcb.20981] [PMID: 16741970]
[122]
Kasten M, Giordano A. CDK10, a Cdc2-related kinase, associates with the Ets2 transcription factor and modulates its transactivation activity. Oncogene 2001; 20(15): 1832-8.
[http://dx.doi.org/10.1038/sj.onc.1204295] [PMID: 11313931]
[123]
Iorns E, Turner NC, Elliott R, et al. Identification of CDK10 as an important determinant of resistance to endocrine therapy for breast cancer. Cancer Cell 2008; 13(2): 91-104.
[http://dx.doi.org/10.1016/j.ccr.2008.01.001] [PMID: 18242510]
[124]
Guen VJ, Gamble C, Flajolet M, et al. CDK10/cyclin M is a protein kinase that controls ETS2 degradation and is deficient in STAR syndrome. Proc Natl Acad Sci 2013; 110(48): 19525-30.
[http://dx.doi.org/10.1073/pnas.1306814110] [PMID: 24218572]
[125]
Zhou Y, Shen JK, Hornicek FJ, Kan Q, Duan Z. The emerging roles and therapeutic potential of cyclin-dependent kinase 11 (CDK11) in human cancer. Oncotarget 2016; 7(26): 40846-59.
[http://dx.doi.org/10.18632/oncotarget.8519] [PMID: 27049727]
[126]
Loyer P, Trembley JH, Grenet JA, et al. Characterization of cyclin L1 and L2 interactions with CDK11 and splicing factors: influence of cyclin L isoforms on splice site selection. J Biol Chem 2008; 283(12): 7721-32.
[http://dx.doi.org/10.1074/jbc.M708188200] [PMID: 18216018]
[127]
Hu D, Mayeda A, Trembley JH, Lahti JM, Kidd VJ. CDK11 complexes promote pre-mRNA splicing. J Biol Chem 2003; 278(10): 8623-9.
[http://dx.doi.org/10.1074/jbc.M210057200] [PMID: 12501247]
[128]
Loyer P, Trembley JH, Lahti JM, Kidd VJ. The RNP protein, RNPS1, associates with specific isoforms of the P34CDC2 related PITSLRE protein kinase in vivo. J Cell Sci 1998; 111(11): 1495-506.
[http://dx.doi.org/10.1242/jcs.111.11.1495] [PMID: 9580558]
[129]
Trembley JH, Hu D, Hsu LC, et al. PITSLRE p110 protein kinases associate with transcription complexes and affect their activity. J Biol Chem 2002; 277(4): 2589-96.
[http://dx.doi.org/10.1074/jbc.M109755200] [PMID: 11709559]
[130]
Beyaert R, Kidd VJ, Cornelis S, et al. Cleavage of PITSLRE kinases by ICE/CASP-1 and CPP32/CASP-3 during apoptosis induced by tumor necrosis factor. J Biol Chem 1997; 272(18): 11694-7.
[http://dx.doi.org/10.1074/jbc.272.18.11694] [PMID: 9115219]
[131]
Mikolajczyk M, Shi J, Vaillancourt RR, Sachs NA, Nelson M. The cyclin-dependent kinase 11p46 isoform interacts with RanBPM. Biochem Biophys Res Commun 2003; 310(1): 14-8.
[http://dx.doi.org/10.1016/j.bbrc.2003.08.116] [PMID: 14511641]
[132]
Shi J, Feng Y, Goulet AC, et al. The p34cdc2-related cyclin-dependent kinase 11 interacts with the p47 subunit of eukaryotic initiation factor 3 during apoptosis. J Biol Chem 2003; 278(7): 5062-71.
[http://dx.doi.org/10.1074/jbc.M206427200] [PMID: 12446680]
[133]
Trembley JH, Loyer P, Hu D, et al. Cyclin dependent kinase 11 in RNA transcription and splicing. Progress in Nucleic Acid Research and Molecular Biology. Elsevier 2004; Vol. 77: pp. 263-88.
[http://dx.doi.org/10.1016/S0079-6603(04)77007-5]
[134]
Franck N, Montembault E, Romé P, Pascal A, Cremet JY, Giet R. CDK11(p58) is required for centriole duplication and Plk4 recruitment to mitotic centrosomes. PLoS One 2011; 6(1): e14600.
[http://dx.doi.org/10.1371/journal.pone.0014600] [PMID: 21297952]
[135]
Petretti C, Savoian M, Montembault E, Glover DM, Prigent C, Giet R. The PITSLRE/CDK11 p58 protein kinase promotes centrosome maturation and bipolar spindle formation. EMBO Rep 2006; 7(4): 418-24.
[http://dx.doi.org/10.1038/sj.embor.7400639] [PMID: 16462731]
[136]
Rakkaa T, Escudé C, Giet R, Magnaghi-Jaulin L, Jaulin C. CDK11p58 kinase activity is required to protect sister chromatid cohesion at centromeres in mitosis. Chromosome Res 2014; 22(3): 267-76.
[http://dx.doi.org/10.1007/s10577-013-9400-x] [PMID: 24436071]
[137]
Yokoyama H, Gruss OJ, Rybina S, et al. CDK11 is a RanGTP-dependent microtubule stabilization factor that regulates spindle assembly rate. J Cell Biol 2008; 180(5): 867-75.
[http://dx.doi.org/10.1083/jcb.200706189] [PMID: 18316407]
[138]
Zhou Y, Han C, Li D, et al. Cyclin-dependent kinase 11p110 (CDK11p110) is crucial for human breast cancer cell proliferation and growth. Sci Rep 2015; 5(1): 10433.
[http://dx.doi.org/10.1038/srep10433] [PMID: 25990212]
[139]
Kren BT, Unger GM, Abedin MJ, et al. Preclinical evaluation of cyclin dependent kinase 11 and casein kinase 2 survival kinases as RNA interference targets for triple negative breast cancer therapy. Breast Cancer Res 2015; 17(1): 19.
[http://dx.doi.org/10.1186/s13058-015-0524-0] [PMID: 25837326]
[140]
Tiedemann RE, Zhu YX, Schmidt J, et al. Identification of molecular vulnerabilities in human multiple myeloma cells by RNA interference lethality screening of the druggable genome. Cancer Res 2012; 72(3): 757-68.
[http://dx.doi.org/10.1158/0008-5472.CAN-11-2781] [PMID: 22147262]
[141]
Tiedemann RE, Zhu YX, Schmidt J, et al. Kinome-wide RNAi studies in human multiple myeloma identify vulnerable kinase targets, including a lymphoid-restricted kinase, GRK6. Blood 2010; 115(8): 1594-604.
[http://dx.doi.org/10.1182/blood-2009-09-243980] [PMID: 19996089]
[142]
Duan Z, Zhang J, Choy E, et al. Systematic kinome shRNA screening identifies CDK11 (PITSLRE) kinase expression is critical for osteosarcoma cell growth and proliferation. Clin Cancer Res 2012; 18(17): 4580-8.
[http://dx.doi.org/10.1158/1078-0432.CCR-12-1157] [PMID: 22791884]
[143]
Feng Y, Sassi S, Shen JK, et al. Targeting CDK11 in osteosarcoma cells using the CRISPR‐cas9 system. J Orthop Res 2015; 33(2): 199-207.
[http://dx.doi.org/10.1002/jor.22745] [PMID: 25348612]
[144]
Jia B, Choy E, Cote G, et al. Cyclin-dependent kinase 11 (CDK11) is crucial in the growth of liposarcoma cells. Cancer Lett 2014; 342(1): 104-12.
[http://dx.doi.org/10.1016/j.canlet.2013.08.040] [PMID: 24007862]
[145]
Clevers H, Nusse R. Wnt/β-catenin signaling and disease. Cell 2012; 149(6): 1192-205.
[http://dx.doi.org/10.1016/j.cell.2012.05.012] [PMID: 22682243]
[146]
Davidson G, Shen J, Huang YL, et al. Cell cycle control of wnt receptor activation. Dev Cell 2009; 17(6): 788-99.
[http://dx.doi.org/10.1016/j.devcel.2009.11.006] [PMID: 20059949]
[147]
Huang J, Deng Q, Wang Q, et al. Exome sequencing of hepatitis B virus–associated hepatocellular carcinoma. Nat Genet 2012; 44(10): 1117-21.
[http://dx.doi.org/10.1038/ng.2391] [PMID: 22922871]
[148]
Leung WKC, Ching AKK, Chan AWH, et al. A novel interplay between oncogenic PFTK1 protein kinase and tumor suppressor TAGLN2 in the control of liver cancer cell motility. Oncogene 2011; 30(44): 4464-75.
[http://dx.doi.org/10.1038/onc.2011.161] [PMID: 21577206]
[149]
Sun T, Co NN, Wong N. PFTK1 interacts with cyclin Y to activate non-canonical Wnt signaling in hepatocellular carcinoma. Biochem Biophys Res Commun 2014; 449(1): 163-8.
[http://dx.doi.org/10.1016/j.bbrc.2014.05.002] [PMID: 24824184]
[150]
Yang L, Zhu J, Huang H, et al. PFTK1 promotes gastric cancer progression by regulating proliferation, migration and invasion. PLoS One 2015; 10(10): e0140451.
[http://dx.doi.org/10.1371/journal.pone.0140451] [PMID: 26488471]
[151]
Shiraishi Y, Fujimoto A, Furuta M, et al. Integrated analysis of whole genome and transcriptome sequencing reveals diverse transcriptomic aberrations driven by somatic genomic changes in liver cancers. PLoS One 2014; 9(12): e114263.
[http://dx.doi.org/10.1371/journal.pone.0114263] [PMID: 25526364]
[152]
Yanagi T, Matsuzawa S. PCTAIRE1/PCTK1/CDK16: A new oncotarget? Cell Cycle 2015; 14(4): 463-4.
[http://dx.doi.org/10.1080/15384101.2015.1006539] [PMID: 25590439]
[153]
Ye X, Zhu C, Harper JW. A premature-termination mutation in the Mus musculus cyclin-dependent kinase 3 gene. Proc Natl Acad Sci 2001; 98(4): 1682-6.
[http://dx.doi.org/10.1073/pnas.98.4.1682] [PMID: 11172011]
[154]
Pozo K, Castro-Rivera E, Tan C, et al. The role of CDK5 in neuroendocrine thyroid cancer. Cancer Cell 2013; 24(4): 499-511.
[http://dx.doi.org/10.1016/j.ccr.2013.08.027] [PMID: 24135281]
[155]
Treiber DK, Shah NP. Ins and outs of kinase DFG motifs. Chem Biol 2013; 20(6): 745-6.
[http://dx.doi.org/10.1016/j.chembiol.2013.06.001] [PMID: 23790484]
[156]
Sánchez-Martínez C, Gelbert LM, Lallena MJ, de Dios A. Cyclin dependent kinase (CDK) inhibitors as anticancer drugs. Bioorg Med Chem Lett 2015; 25(17): 3420-35.
[http://dx.doi.org/10.1016/j.bmcl.2015.05.100] [PMID: 26115571]
[157]
Rana S, Sonawane YA, Taylor MA, Kizhake S, Zahid M, Natarajan A. Synthesis of aminopyrazole analogs and their evaluation as CDK inhibitors for cancer therapy. Bioorg Med Chem Lett 2018; 28(23-24): 3736-40.
[http://dx.doi.org/10.1016/j.bmcl.2018.10.020] [PMID: 30343954]
[158]
Ganga Reddy V, Srinivasa Reddy T, Lakshma Nayak V, et al. Design, synthesis and biological evaluation of N -((1-benzyl-1 H -1,2,3-triazol-4-yl)methyl)-1,3-diphenyl-1 H -pyrazole-4-carboxamides as CDK1/Cdc2 inhibitors. Eur J Med Chem 2016; 122: 164-77.
[http://dx.doi.org/10.1016/j.ejmech.2016.06.011] [PMID: 27344493]
[159]
Ali GME, Ibrahim DA, Elmetwali AM, Ismail NSM. Design, synthesis and biological evaluation of certain CDK2 inhibitors based on pyrazole and pyrazolo[1,5-a] pyrimidine scaffold with apoptotic activity. Bioorg Chem 2019; 86: 1-14.
[http://dx.doi.org/10.1016/j.bioorg.2019.01.008] [PMID: 30682722]
[160]
Oudah KH, Najm MAA, Samir N, Serya RAT, Abouzid KAM. Design, synthesis and molecular docking of novel pyrazolo[1,5-a][1,3,5]triazine derivatives as CDK2 inhibitors. Bioorg Chem 2019; 92: 103239.
[http://dx.doi.org/10.1016/j.bioorg.2019.103239] [PMID: 31513938]
[161]
Abdel Latif NA, Batran RZ, Khedr MA, Abdalla MM. 3-Substituted-4-hydroxycoumarin as a new scaffold with potent CDK inhibition and promising anticancer effect: Synthesis, molecular modeling and QSAR studies. Bioorg Chem 2016; 67: 116-29.
[http://dx.doi.org/10.1016/j.bioorg.2016.06.005] [PMID: 27372186]
[162]
Abd El-Karim SS, Syam YM, El Kerdawy AM, Abdelghany TM. New thiazol-hydrazono-coumarin hybrids targeting human cervical cancer cells: Synthesis, CDK2 inhibition, QSAR and molecular docking studies. Bioorg Chem 2019; 86: 80-96.
[http://dx.doi.org/10.1016/j.bioorg.2019.01.026] [PMID: 30685646]
[163]
Pathoor R, Bahulayan D. MCR-click synthesis, molecular docking and cytotoxicity evaluation of a new series of indole–triazole–coumarin hybrid peptidomimetics. New J Chem 2018; 42(9): 6810-6.
[http://dx.doi.org/10.1039/C8NJ00032H]
[164]
Singh U, Chashoo G, Khan SU, et al. Design of novel 3-pyrimidinylazaindole CDK2/9 inhibitors with potent in vitro and in vivo antitumor efficacy in a triple-negative breast cancer model. J Med Chem 2017; 60(23): 9470-89.
[http://dx.doi.org/10.1021/acs.jmedchem.7b00663] [PMID: 29144137]
[165]
Diao PC, Lin WY, Jian XE, Li YH, You WW, Zhao PL. Discovery of novel pyrimidine-based benzothiazole derivatives as potent cyclin-dependent kinase 2 inhibitors with anticancer activity. Eur J Med Chem 2019; 179: 196-207.
[http://dx.doi.org/10.1016/j.ejmech.2019.06.055] [PMID: 31254921]
[166]
Wang Y, Chen Y, Cheng X, et al. Design, synthesis and biological evaluation of pyrimidine derivatives as novel CDK2 inhibitors that induce apoptosis and cell cycle arrest in breast cancer cells. Bioorg Med Chem 2018; 26(12): 3491-501.
[http://dx.doi.org/10.1016/j.bmc.2018.05.024] [PMID: 29853338]
[167]
Vymětalová L, Havlíček L, Šturc A, et al. 5-Substituted 3-isopropyl-7-[4-(2-pyridyl)benzyl]amino-1(2)H-pyrazolo[4,3-d]pyrimidines with anti-proliferative activity as potent and selective inhibitors of cyclin-dependent kinases. Eur J Med Chem 2016; 110: 291-301.
[http://dx.doi.org/10.1016/j.ejmech.2016.01.011] [PMID: 26851505]
[168]
Hu X, Zhao H, Wang Y, Liu Z, Feng B, Tang C. Synthesis and biological evaluation of novel 5,6-dihydropyrimido[4,5-f]quinazoline derivatives as potent CDK2 inhibitors. Bioorg Med Chem Lett 2018; 28(20): 3385-90.
[http://dx.doi.org/10.1016/j.bmcl.2018.08.035] [PMID: 30197029]
[169]
Ghorab MM, Ragab FA, Heiba HI, Elsayed MSA, Ghorab WM. Design, synthesis and molecular modeling study of certain 4-Methylbenzenesulfonamides with CDK2 inhibitory activity as anticancer and radio-sensitizing agents. Bioorg Chem 2018; 80: 276-87.
[http://dx.doi.org/10.1016/j.bioorg.2018.06.010] [PMID: 29966874]
[170]
Cherukupalli S, Chandrasekaran B, Kryštof V, et al. Synthesis, anticancer evaluation, and molecular docking studies of some novel 4,6-disubstituted pyrazolo[3,4-d]pyrimidines as cyclin-dependent kinase 2 (CDK2) inhibitors. Bioorg Chem 2018; 79: 46-59.
[http://dx.doi.org/10.1016/j.bioorg.2018.02.030] [PMID: 29753773]
[171]
Cherukupalli S, Chandrasekaran B, Aleti RR, et al. Synthesis of 4,6-disubstituted pyrazolo[3,4-d]pyrimidine analogues: Cyclin-dependent kinase 2 (CDK2) inhibition, molecular docking and anticancer evaluation. J Mol Struct 2019; 1176: 538-51.
[http://dx.doi.org/10.1016/j.molstruc.2018.08.104]
[172]
Cortese D, Chegaev K, Guglielmo S, et al. Synthesis and biological evaluation of N 2 ‐Substituted 2,4‐Diamino‐6‐cyclohexylmethoxy‐5] ‐nitrosopyrimidines and related 5‐cyano‐nno‐azoxy derivatives as cyclin‐dependent kinase 2 (CDK2) inhibitors. ChemMedChem 2016; 11(16): 1705-8.
[http://dx.doi.org/10.1002/cmdc.201600108] [PMID: 27355194]
[173]
Vekariya MK, Vekariya RH, Brahmkshatriya PS, Shah NK. Pyrimidine‐based pyrazoles as cyclin‐dependent kinase 2 inhibitors: Design, synthesis, and biological evaluation. Chem Biol Drug Des 2018; 92(3): 1683-91.
[http://dx.doi.org/10.1111/cbdd.13334] [PMID: 29767460]
[174]
Wu YZ, Ying HZ, Xu L, et al. Design, synthesis, and molecular docking study of 3 H ‐imidazole[4,5‐ c]pyridine derivatives as CDK2 inhibitors. Arch Pharm 2018; 351(6): 1700381.
[http://dx.doi.org/10.1002/ardp.201700381] [PMID: 29708285]
[175]
Xu X, Yao Q. Scaffold hopping approach to a new series of pyridine derivatives as potent inhibitors of CDK2. Arch Pharm 2016; 349(3): 224-31.
[http://dx.doi.org/10.1002/ardp.201500335] [PMID: 26871934]
[176]
Shamsiya A, Damodaran B. A click strategy for the synthesis of fluorescent pyrimidinone‐triazole hybrids with CDK2 selectivity in hela and A549 cell lines. ChemistrySelect 2019; 4(11): 3076-82.
[http://dx.doi.org/10.1002/slct.201803748]
[177]
Nassar IF, El Farargy AF, Abdelrazek FM, Ismail NSM. Design, synthesis and anticancer evaluation of novel pyrazole, pyrazolo[3,4- d]pyrimidine and their glycoside derivatives. Nucleosides Nucleotides Nucleic Acids 2017; 36(4): 275-91.
[http://dx.doi.org/10.1080/15257770.2016.1276290] [PMID: 28323527]
[178]
El-Hameed RHA, Sayed AI. Synthesis of novel pyrrolopyrimidine derivatives as CDK2 inhibitors. Pharmacophore 2018; 9(5): 29-49.
[179]
Khair NZ, Lenjisa JL, Tadesse S, et al. Discovery of CDK5 Inhibitors through Structure-Guided Approach. ACS Med Chem Lett 2019; 10(5): 786-91.
[http://dx.doi.org/10.1021/acsmedchemlett.9b00029] [PMID: 31098000]
[180]
Ajani H, Jansa J, Köprülüoğlu C. Imidazo[1,2‐ c]pyrimidin‐5(6 H)‐one as a novel core of cyclin‐dependent kinase 2 inhibitors: Synthesis, activity measurement, docking, and quantum mechanical scoring. J Mol Recognit 2018; 31(9): e2720.
[http://dx.doi.org/10.1002/jmr.2720] [PMID: 29687635]
[181]
Jing L, Tang Y, Xiao Z. Discovery of novel CDK inhibitors via scaffold hopping from CAN508. Bioorg Med Chem Lett 2018; 28(8): 1386-91.
[http://dx.doi.org/10.1016/j.bmcl.2018.02.054] [PMID: 29550093]
[182]
Jorda R, Havlíček J, Šturc A. 3,5,7-substituted pyrazolo[4,3- d]pyrimidine inhibitors of cyclin-dependent kinases and their evaluation in lymphoma models. J Med Chem 2019; 62(9): 4606-23.
[http://dx.doi.org/10.1021/acs.jmedchem.9b00189] [PMID: 30943029]
[183]
Coxon CR, Anscombe E, Harnor SJ, et al. Cyclin-dependent kinase (CDK) inhibitors: Structure–activity relationships and insights into the CDK-2 selectivity of 6-substituted 2-arylaminopurines. J Med Chem 2017; 60(5): 1746-67.
[http://dx.doi.org/10.1021/acs.jmedchem.6b01254] [PMID: 28005359]
[184]
Yun F, Cheng C, Ullah S, Yuan Q. Design, synthesis and biological evaluation of novel histone deacetylase1/2 (HDAC1/2) and cyclin-dependent Kinase2 (CDK2) dual inhibitors against malignant cancer. Eur J Med Chem 2020; 198: 112322.
[http://dx.doi.org/10.1016/j.ejmech.2020.112322] [PMID: 32361064]
[185]
Parrino B, Attanzio A, Spanò V, et al. Synthesis, antitumor activity and CDK1 inhibiton of new thiazole nortopsentin analogues. Eur J Med Chem 2017; 138: 371-83.
[http://dx.doi.org/10.1016/j.ejmech.2017.06.052] [PMID: 28688277]
[186]
Baltus CB, Jorda R, Marot C, et al. Synthesis, biological evaluation and molecular modeling of a novel series of 7-azaindole based tri-heterocyclic compounds as potent CDK2/Cyclin E inhibitors. Eur J Med Chem 2016; 108: 701-19.
[http://dx.doi.org/10.1016/j.ejmech.2015.12.023] [PMID: 26741853]
[187]
Park SJ, Kim E, Yoo M, et al. Synthesis and biological evaluation of N9-cis-cyclobutylpurine derivatives for use as cyclin-dependent kinase (CDK) inhibitors. Bioorg Med Chem Lett 2017; 27(18): 4399-404.
[http://dx.doi.org/10.1016/j.bmcl.2017.08.018] [PMID: 28827110]
[188]
Jing L, Tang Y, Goto M, Lee KH, Xiao Z. SAR study on N2, N4 -disubstituted pyrimidine-2,4-diamines as effective CDK2/CDK9 inhibitors and antiproliferative agents. RSC Advances 2018; 8(22): 11871-85.
[http://dx.doi.org/10.1039/C8RA01440J] [PMID: 29682280]
[189]
Rahman AAHA, Nassar IF, Shaban AKF. EL-Kady DS, Awad HM, El Sayed WA. Synthesis, Docking Studies into CDK-2 and Anticancer Activity of New Derivatives Based Pyrimidine Scaffold and Their Derived Glycosides. Mini Rev Med Chem 2019; 19(13): 1093-110.
[http://dx.doi.org/10.2174/1389557519666190312165717] [PMID: 30864522]
[190]
Yin L, Li H, Liu W, et al. A highly potent CDK4/6 inhibitor was rationally designed to overcome blood brain barrier in gliobastoma therapy. Eur J Med Chem 2018; 144: 1-28.
[http://dx.doi.org/10.1016/j.ejmech.2017.12.003] [PMID: 29247857]
[191]
Shi C, Wang Q, Liao X, et al. Discovery of 6-(2-(dimethylamino)] ethyl)-N-(5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]] imidazole-6-yl)pyrimidin-2-yl)-5,6,7,8-tetrahydro-1,6-naphthyridin] -2-amine as a highly potent cyclin-dependent kinase 4/6 inhibitor for treatment of cancer. Eur J Med Chem 2019; 178: 352-64.
[http://dx.doi.org/10.1016/j.ejmech.2019.06.005] [PMID: 31200237]
[192]
Bronner SM, Merrick KA, Murray J, et al. Design of a brain-penetrant CDK4/6 inhibitor for glioblastoma. Bioorg Med Chem Lett 2019; 29(16): 2294-301.
[http://dx.doi.org/10.1016/j.bmcl.2019.06.021] [PMID: 31307887]
[193]
Wang Y, Liu WJ, Yin L, et al. Design and synthesis of 4-(2,3-dihydro-1 H -benzo[d]pyrrolo[1,2- a]imidazol-7-yl)- N -(5-(piperazin-1-ylmethyl)pyridine-2-yl)pyrimidin-2-amine as a highly potent and selective cyclin-dependent kinases 4 and 6 inhibitors and the discovery of structure-activity relationships. Bioorg Med Chem Lett 2018; 28(5): 974-8.
[http://dx.doi.org/10.1016/j.bmcl.2017.12.068] [PMID: 29429832]
[194]
Zha C, Deng W, Fu Y, et al. Design, synthesis and biological evaluation of tetrahydronaphthyridine derivatives as bioavailable CDK4/6 inhibitors for cancer therapy. Eur J Med Chem 2018; 148: 140-53.
[http://dx.doi.org/10.1016/j.ejmech.2018.02.022] [PMID: 29459274]
[195]
Tadesse S, Yu M, Mekonnen LB, et al. Highly Potent, Selective, and Orally Bioavailable 4-Thiazol- N -(pyridin-2-yl)pyrimidin-2-amine Cyclin-Dependent Kinases 4 and 6 Inhibitors as Anticancer Drug Candidates: Design, Synthesis, and Evaluation. J Med Chem 2017; 60(5): 1892-915.
[http://dx.doi.org/10.1021/acs.jmedchem.6b01670] [PMID: 28156111]
[196]
Tadesse S, Bantie L, Tomusange K, et al. Discovery and pharmacological characterization of a novel series of highly selective inhibitors of cyclin‐dependent kinases 4 and 6 as anticancer agents. Br J Pharmacol 2018; 175(12): 2399-413.
[http://dx.doi.org/10.1111/bph.13974] [PMID: 28800675]
[197]
Zhao H, Hu X, Cao K, et al. Synthesis and SAR of 4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline derivatives as potent and selective CDK4/6 inhibitors. Eur J Med Chem 2018; 157: 935-45.
[http://dx.doi.org/10.1016/j.ejmech.2018.08.043] [PMID: 30165341]
[198]
Jorda R, Schütznerová E. Cankař P, Brychtová V, Navrátilová J, Kryštof V. Novel arylazopyrazole inhibitors of cyclin-dependent kinases. Bioorg Med Chem 2015; 23(9): 1975-81.
[http://dx.doi.org/10.1016/j.bmc.2015.03.025] [PMID: 25835357]
[199]
Kamal A, Mahesh R, Nayak VL, et al. Discovery of pyrrolospirooxindole derivatives as novel cyclin dependent kinase 4 (CDK4) inhibitors by catalyst-free, green approach. Eur J Med Chem 2016; 108: 476-85.
[http://dx.doi.org/10.1016/j.ejmech.2015.11.046] [PMID: 26708114]
[200]
Chiou CT, Lee WC, Liao JH, et al. Synthesis and evaluation of 3-ylideneoxindole acetamides as potent anticancer agents. Eur J Med Chem 2015; 98: 1-12.
[http://dx.doi.org/10.1016/j.ejmech.2015.04.062] [PMID: 25988923]
[201]
He D, Yang ZQ, Hou M. Design, synthesis and activity evaluation of some novel indole derivatives. Asian J Chem 2015; 27(5): 1729-34.
[http://dx.doi.org/10.14233/ajchem.2015.17583]
[202]
Li Y, Guo Q, Zhang C, et al. Discovery of a highly potent, selective and novel CDK9 inhibitor as an anticancer drug candidate. Bioorg Med Chem Lett 2017; 27(15): 3231-7.
[http://dx.doi.org/10.1016/j.bmcl.2017.06.041] [PMID: 28651979]
[203]
Czudor Z, Balogh M, Bánhegyi P, et al. Novel compounds with potent CDK9 inhibitory activity for the treatment of myeloma. Bioorg Med Chem Lett 2018; 28(4): 769-73.
[http://dx.doi.org/10.1016/j.bmcl.2018.01.002] [PMID: 29329658]
[204]
Ghanem NM, Farouk F, George RF, Abbas SES, El-Badry OM. Design and synthesis of novel imidazo[4,5-b]pyridine based compounds as potent anticancer agents with CDK9 inhibitory activity. Bioorg Chem 2018; 80: 565-76.
[http://dx.doi.org/10.1016/j.bioorg.2018.07.006] [PMID: 30025343]
[205]
Wang B, Wu J, Wu Y, et al. Discovery of 4-(((4-(5-chloro-2-(((1s,4s)-4-((2-methoxyethyl)amino)cyclohexyl)amino)pyridin-4-yl)thiazol-2-yl)amino)methyl)tetrahydro-2H-pyran-4-carbonitrile (JSH-150) as a novel highly selective and potent CDK9 kinase inhibitor. Eur J Med Chem 2018; 158: 896-916.
[http://dx.doi.org/10.1016/j.ejmech.2018.09.025] [PMID: 30253346]
[206]
Wang X, Yu C, Wang C, et al. Novel cyclin-dependent kinase 9 (CDK9) inhibitor with suppression of cancer stemness activity against non-small-cell lung cancer. Eur J Med Chem 2019; 181: 111535.
[http://dx.doi.org/10.1016/j.ejmech.2019.07.038] [PMID: 31376566]
[207]
Fujimoto J, Hirayama T, Hirata Y, et al. Studies of CDK 8/19 inhibitors: Discovery of novel and selective CDK8/19 dual inhibitors and elimination of their CYP3A4 time-dependent inhibition potential. Bioorg Med Chem 2017; 25(12): 3018-33.
[http://dx.doi.org/10.1016/j.bmc.2017.03.049] [PMID: 28392276]
[208]
Han X, Jiang M, Zhou C, et al. Discovery of potent and selective CDK8 inhibitors through FBDD approach. Bioorg Med Chem Lett 2017; 27(18): 4488-92.
[http://dx.doi.org/10.1016/j.bmcl.2017.07.080] [PMID: 28802632]
[209]
Bergeron P, Koehler MFT, Blackwood EM, et al. Design and development of a series of potent and selective type ii inhibitors of CDK8. ACS Med Chem Lett 2016; 7(6): 595-600.
[http://dx.doi.org/10.1021/acsmedchemlett.6b00044] [PMID: 27326333]
[210]
Mallinger A, Schiemann K, Rink C, et al. Discovery of potent, selective, and orally bioavailable small-molecule modulators of the mediator complex-associated kinases CDK8 and CDK19. J Med Chem 2016; 59(3): 1078-101.
[http://dx.doi.org/10.1021/acs.jmedchem.5b01685] [PMID: 26796641]
[211]
He LJ, Zhu YB, Fan QZ, et al. Shape-based virtual screen for the discovery of novel CDK8 inhibitor chemotypes. Bioorg Med Chem Lett 2019; 29(4): 549-55.
[http://dx.doi.org/10.1016/j.bmcl.2018.12.065] [PMID: 30630717]
[212]
Wang J, Ge R, Qiu X, et al. Discovery and synthesis of novel Wogonin derivatives with potent antitumor activity in vitro. Eur J Med Chem 2017; 140: 421-34.
[http://dx.doi.org/10.1016/j.ejmech.2017.09.046] [PMID: 28987604]
[213]
Wang J, Li T, Zhao T, et al. Design of wogonin-inspired selective cyclin-dependent kinase 9 (CDK9) inhibitors with potent in vitro and in vivo antitumor activity. Eur J Med Chem 2019; 178: 782-801.
[http://dx.doi.org/10.1016/j.ejmech.2019.06.024] [PMID: 31238183]
[214]
Bharate SB, Kumar V, Jain SK, et al. Discovery and preclinical development of IIIM-290, an orally active potent cyclin-dependent kinase inhibitor. J Med Chem 2018; 61(4): 1664-87.
[http://dx.doi.org/10.1021/acs.jmedchem.7b01765] [PMID: 29370702]
[215]
Koehler MFT, Bergeron P, Blackwood EM, et al. Development of a potent, specific CDK8 kinase inhibitor which phenocopies CDK8/19 knockout cells. ACS Med Chem Lett 2016; 7(3): 223-8.
[http://dx.doi.org/10.1021/acsmedchemlett.5b00278] [PMID: 26985305]
[216]
Ono K, Banno H, Okaniwa M, et al. Design and synthesis of selective CDK8/19 dual inhibitors: Discovery of 4,5-dihydrothieno[3′4′3,4]benzo[1,2- d]isothiazole derivatives. Bioorg Med Chem 2017; 25(8): 2336-50.
[http://dx.doi.org/10.1016/j.bmc.2017.02.038] [PMID: 28302507]
[217]
Yan L, Lai F, Chen X, Xiao Z. Discovery of novel indirubin-3′-monoxime derivatives as potent inhibitors against CDK2 and CDK9. Bioorg Med Chem Lett 2015; 25(11): 2447-51.
[http://dx.doi.org/10.1016/j.bmcl.2015.03.066] [PMID: 25908517]
[218]
Ferguson FM, Doctor ZM, Ficarro SB, et al. Discovery of covalent CDK14 inhibitors with pan-TAIRE family specificity. Cell Chem Biol 2019; 26(6): 804-817.e12.
[http://dx.doi.org/10.1016/j.chembiol.2019.02.015] [PMID: 30930164]
[219]
Gao J, Fang C, Xiao Z, et al. Discovery of novel 5-fluoro- N2, N4 -diphenylpyrimidine-2,4-diamines as potent inhibitors against CDK2 and CDK9. MedChemComm 2015; 6(3): 444-54.
[http://dx.doi.org/10.1039/C4MD00412D] [PMID: 25914804]
[220]
Li Y, Luo X, Guo Q, et al. Discovery of N 1-(4-((7-Cyclopentyl-6-(dimethylcarbamoyl)-7 H -pyrrolo[2,3- d]pyrimidin-2-yl)amino)phenyl)- N 8-hydroxyoctanediamide as a Novel Inhibitor Targeting Cyclin-dependent Kinase 4/9 (CDK4/9) and Histone Deacetlyase1 (HDAC1) against Malignant Cancer. J Med Chem 2018; 61(7): 3166-92.
[http://dx.doi.org/10.1021/acs.jmedchem.8b00209] [PMID: 29518312]
[221]
Huang Z, Zhao B, Qin Z, et al. Novel dual inhibitors targeting CDK4 and VEGFR2 synergistically suppressed cancer progression and angiogenesis. Eur J Med Chem 2019; 181: 111541.
[http://dx.doi.org/10.1016/j.ejmech.2019.07.044] [PMID: 31382120]
[222]
Malki WH, Gouda AM, Ali HEA, et al. Structural-based design, synthesis, and antitumor activity of novel alloxazine analogues with potential selective kinase inhibition. Eur J Med Chem 2018; 152: 31-52.
[http://dx.doi.org/10.1016/j.ejmech.2018.04.029] [PMID: 29684708]
[223]
Řezníčková E, Weitensteiner S, Havlíček L, et al. Characterization of a Pyrazolo[4,3‐d]pyrimidine Inhibitor of Cyclin‐Dependent Kinases 2 and 5 and Aurora A With Pro‐Apoptotic and Anti‐Angiogenic Activity In Vitro. Chem Biol Drug Des 2015; 86(6): 1568-40.
[http://dx.doi.org/10.1111/cbdd.12618] [PMID: 26198005]
[224]
Huang X. Synthesis and biological evaluation of 3-aryl pyrazoles as CDK2/HDAC inhibitor for anticancer agents. J Drug Des & Med Chem 2016; 2(4): 40.
[http://dx.doi.org/10.11648/j.jddmc.20160204.12]
[225]
Phillipson LJ, Segal DH, Nero TL, et al. Discovery and SAR of novel pyrazolo[1,5-a]pyrimidines as inhibitors of CDK9. Bioorg Med Chem 2015; 23(19): 6280-96.
[http://dx.doi.org/10.1016/j.bmc.2015.08.035] [PMID: 26349627]
[226]
Boulahjar R, Ouach A, Bourg S, et al. Advances in tetrahydropyrido[1,2- a]isoindolone (valmerins) series: Potent glycogen synthase kinase 3 and cyclin dependent kinase 5 inhibitors. Eur J Med Chem 2015; 101: 274-87.
[http://dx.doi.org/10.1016/j.ejmech.2015.06.046] [PMID: 26142492]
[227]
Ouach A, Boulahjar R, Vala C, et al. Novel optimization of valmerins (tetrahydropyrido[1,2-a]isoindolones) as potent dual CDK5/GSK3 inhibitors. Eur J Med Chem 2016; 115: 311-25.
[http://dx.doi.org/10.1016/j.ejmech.2016.02.072] [PMID: 27019296]
[228]
Yu Y, Ran D, Jiang J, et al. Discovery of novel 9H-purin derivatives as dual inhibitors of HDAC1 and CDK2. Bioorg Med Chem Lett 2019; 29(16): 2136-40.
[http://dx.doi.org/10.1016/j.bmcl.2019.06.059] [PMID: 31272794]
[229]
Sonawane V, Mohd Siddique MU, Jadav SS, Sinha BN, Jayaprakash V, Chaudhuri B. Cink4T, a quinazolinone-based dual inhibitor of CDK4 and tubulin polymerization, identified via ligand-based virtual screening, for efficient anticancer therapy. Eur J Med Chem 2019; 165: 115-32.
[http://dx.doi.org/10.1016/j.ejmech.2019.01.011] [PMID: 30665142]
[230]
Gu S, Cui D, Chen X, Xiong X, Zhao Y. PROTACs: An emerging targeting technique for protein degradation in drug discovery. BioEssays 2018; 40(4): 1700247.
[http://dx.doi.org/10.1002/bies.201700247] [PMID: 29473971]
[231]
Toure M, Crews CM. Small‐molecule PROTACS: New approaches to protein degradation. Angew Chem Int Ed 2016; 55(6): 1966-73.
[http://dx.doi.org/10.1002/anie.201507978] [PMID: 26756721]
[232]
Dogan S, Shen R, Ang DC, et al. Molecular epidemiology of EGFR and KRAS mutations in 3,026 lung adenocarcinomas: Higher susceptibility of women to smoking-related KRAS-mutant cancers. Clin Cancer Res 2012; 18(22): 6169-77.
[http://dx.doi.org/10.1158/1078-0432.CCR-11-3265] [PMID: 23014527]
[233]
Lai AC, Crews CM. Induced protein degradation: an emerging drug discovery paradigm. Nat Rev Drug Discov 2017; 16(2): 101-14.
[http://dx.doi.org/10.1038/nrd.2016.211] [PMID: 27885283]
[234]
Leiser D, Pochon B, Blank-Liss W, et al. Targeting of the MET receptor tyrosine kinase by small molecule inhibitors leads to MET accumulation by impairing the receptor downregulation. FEBS Lett 2014; 588(5): 653-8.
[http://dx.doi.org/10.1016/j.febslet.2013.12.025] [PMID: 24440350]
[235]
Spiegel J, Cromm PM, Zimmermann G, Grossmann TN, Waldmann H. Small-molecule modulation of Ras signaling. Nat Chem Biol 2014; 10(8): 613-22.
[http://dx.doi.org/10.1038/nchembio.1560] [PMID: 24929527]
[236]
Li X, Song Y. Proteolysis-targeting chimera (PROTAC) for targeted protein degradation and cancer therapy. J Hematol Oncol 2020; 13(1): 50.
[http://dx.doi.org/10.1186/s13045-020-00885-3] [PMID: 32404196]
[237]
Gadd MS, Testa A, Lucas X, et al. Structural basis of PROTAC cooperative recognition for selective protein degradation. Nat Chem Biol 2017; 13(5): 514-21.
[http://dx.doi.org/10.1038/nchembio.2329] [PMID: 28288108]
[238]
Gao H, Sun X, Rao Y. PROTAC Technology: Opportunities and challenges. ACS Med Chem Lett 2020; 11(3): 237-40.
[http://dx.doi.org/10.1021/acsmedchemlett.9b00597] [PMID: 32184950]
[239]
Zhao B, Burgess K. PROTACs suppression of CDK4/6, crucial kinases for cell cycle regulation in cancer. Chem Commun 2019; 55(18): 2704-7.
[http://dx.doi.org/10.1039/C9CC00163H] [PMID: 30758029]
[240]
Brand M, Jiang B, Bauer S, et al. Homolog-selective degradation as a strategy to probe the function of CDK6 in AML. Cell Chem Biol 2019; 26(2): 300-306.e9.
[http://dx.doi.org/10.1016/j.chembiol.2018.11.006] [PMID: 30595531]
[241]
Jiang B, Wang ES, Donovan KA, et al. Development of dual and selective degraders of cyclin‐dependent kinases 4 and 6. Angew Chem Int Ed 2019; 58(19): 6321-6.
[http://dx.doi.org/10.1002/anie.201901336] [PMID: 30802347]
[242]
Rana S, Bendjennat M, Kour S, et al. Selective degradation of CDK6 by a palbociclib based PROTAC. Bioorg Med Chem Lett 2019; 29(11): 1375-9.
[http://dx.doi.org/10.1016/j.bmcl.2019.03.035] [PMID: 30935795]
[243]
Su S, Yang Z, Gao H, et al. Potent and preferential degradation of CDK6 via proteolysis targeting chimera degraders. J Med Chem 2019; 62(16): 7575-82.
[http://dx.doi.org/10.1021/acs.jmedchem.9b00871] [PMID: 31330105]
[244]
Anderson NA, Cryan J, Ahmed A, et al. Selective CDK6 degradation mediated by cereblon, VHL, and novel IAP-recruiting PROTACs. Bioorg Med Chem Lett 2020; 30(9): 127106.
[http://dx.doi.org/10.1016/j.bmcl.2020.127106] [PMID: 32184044]
[245]
Hatcher JM, Wang ES, Johannessen L, Kwiatkowski N, Sim T, Gray NS. Development of highly potent and selective steroidal inhibitors and degraders of CDK8. ACS Med Chem Lett 2018; 9(6): 540-5.
[http://dx.doi.org/10.1021/acsmedchemlett.8b00011] [PMID: 29937979]
[246]
Robb CM, Contreras JI, Kour S, et al. Chemically induced degradation of CDK9 by a proteolysis targeting chimera (PROTAC). Chem Commun 2017; 53(54): 7577-80.
[http://dx.doi.org/10.1039/C7CC03879H] [PMID: 28636052]
[247]
Olson CM, Jiang B, Erb MA, et al. Pharmacological perturbation of CDK9 using selective CDK9 inhibition or degradation. Nat Chem Biol 2018; 14(2): 163-70.
[http://dx.doi.org/10.1038/nchembio.2538] [PMID: 29251720]
[248]
Bian J, Ren J, Li Y, et al. Discovery of Wogonin-based PROTACs against CDK9 and capable of achieving antitumor activity. Bioorg Chem 2018; 81: 373-81.
[http://dx.doi.org/10.1016/j.bioorg.2018.08.028] [PMID: 30196207]
[249]
Zhou F, Chen L, Cao C, et al. Development of selective mono or dual PROTAC degrader probe of CDK isoforms. Eur J Med Chem 2020; 187: 111952.
[http://dx.doi.org/10.1016/j.ejmech.2019.111952] [PMID: 31846828]
[250]
Wei M, Zhao R, Cao Y, et al. First orally bioavailable prodrug of proteolysis targeting chimera (PROTAC) degrades cyclin-dependent kinases 2/4/6 in vivo. Eur J Med Chem 2021; 209: 112903.
[http://dx.doi.org/10.1016/j.ejmech.2020.112903] [PMID: 33256948]
[251]
De Dominici M, Porazzi P, Xiao Y, et al. Selective inhibition of Ph-positive all cell growth through kinase-dependent and -independent effects by CDK6-specific PROTACs. Blood 2020; 135(18): 1560-73.
[http://dx.doi.org/10.1182/blood.2019003604] [PMID: 32040545]
[252]
Steinebach C, Ng YLD, Sosič I. Systematic exploration of different E3 ubiquitin ligases: An approach towards potent and selective CDK6 degraders. Chem Sci 2020; 11(13): 3474-86.
[http://dx.doi.org/10.1039/D0SC00167H] [PMID: 33133483]
[253]
Qiu X, Li Y, Yu B, et al. Discovery of selective CDK9 degraders with enhancing antiproliferative activity through PROTAC conversion. Eur J Med Chem 2021; 211: 113091.
[http://dx.doi.org/10.1016/j.ejmech.2020.113091] [PMID: 33338869]
[254]
Marak BN, Dowarah J, Khiangte L, Singh VP. A comprehensive insight on the recent development of Cyclic Dependent Kinase inhibitors as anticancer agents. Eur J Med Chem 2020; 203: 112571.
[http://dx.doi.org/10.1016/j.ejmech.2020.112571] [PMID: 32707525]
[255]
Whittaker SR, Mallinger A, Workman P, Clarke PA. Inhibitors of cyclin-dependent kinases as cancer therapeutics. Pharmacol Ther 2017; 173: 83-105.
[http://dx.doi.org/10.1016/j.pharmthera.2017.02.008] [PMID: 28174091]

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