Login Register Cart 0
Generic placeholder image

Current Topics in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Discovery of Tropomyosin Receptor Kinase Inhibitors as New Generation Anticancer Agents: A Review

Author(s): Ishan Panchal*, Rati Kailash Prasad Tripathi, Kinjal Parmar and Mange Ram Yadav

Volume 24, Issue 1, 2024

Published on: 06 December, 2023

Page: [3 - 30] Pages: 28

DOI: 10.2174/0115680266271225231203164309

Price: $65

Abstract

Background: The tropomyosin receptor kinases (TRKs) are crucial for many cellular functions, such as growth, motility, differentiation, and metabolism. Abnormal TRK signalling contributes to a variety of human disorders, most evidently cancer. Comprehensive genomic studies have found numerous changes in the genes that code for TRKs like MET, HER2/ErbB2, and EGFR, among many others. Precision medicine resistance, relapse occurring because of the protein point mutations, and the existence of multiple molecular feedback loops are significant therapeutic hurdles to the long-term effectiveness of TRK inhibitors as general therapeutic agents for the treatment of cancer.

Objective: This review is carried out to highlight the role of tropomyosin receptor kinase in cancer and the function of TRK inhibitors in the intervention of cancer.

Methods: Literature research has been accomplished using Google Scholar and databases like ScienceDirect, WOS, PubMed, SciFinder, and Scopus.

Results: In this review, we provide an overview of the main molecular and functional properties of TRKs and their inhibitors. It also discusses how these advancements have affected the development and use of novel treatments for malignancies and other conditions caused by activated TRKs. Several therapeutic strategies, including the discovery and development of small-molecule TRK inhibitors belonging to various chemical classes and their activity, as well as selectivity towards the receptors, have been discussed in detail.

Conclusion: This review will help the researchers gain a fundamental understanding of TRKs, how this protein family works, and the ways to create chemical moieties, such as TRK inhibitors, which can serve as tailored therapies for cancer.

« Previous Next »
Graphical Abstract

[1]
Børset, M. Tumour-agnostic drugs and future cancer treatment. Tidsskr. Nor. Laegeforen., 2019, 139(5), 1-3.
[PMID: 30872821]
[2]
Enjalbert, A.; Pechon-Valle, C.L. Protein kinasesEncyclopedia of Hormones; Elsevier: Amsterdam, 2003.
[http://dx.doi.org/10.1016/B0-12-341103-3/00258-8]
[3]
Bailey, J.J.; Jaworski, C.; Tung, D.; Wängler, C.; Wängler, B.; Schirrmacher, R. Tropomyosin receptor kinase inhibitors: An updated patent review for 2016-2019. Expert Opin. Ther. Pat., 2020, 30(5), 325-339.
[http://dx.doi.org/10.1080/13543776.2020.1737011] [PMID: 32129124]
[4]
Reichardt, L.F. Neurotrophin-regulated signalling pathways. Philos. Trans. R. Soc. Lond. B Biol. Sci., 2006, 361(1473), 1545-1564.
[http://dx.doi.org/10.1098/rstb.2006.1894] [PMID: 16939974]
[5]
Huang, E.J.; Reichardt, L.F. Neurotrophins: Roles in neuronal development and function. Annu. Rev. Neurosci., 2001, 24(1), 677-736.
[http://dx.doi.org/10.1146/annurev.neuro.24.1.677] [PMID: 11520916]
[6]
Weier, H.U.G.; Rhein, A.P.; Shadravan, F.; Collins, C.; Polikoff, D. Rapid physical mapping of the human trk protooncogene (NTRK1) to human chromosome 1q21-q22 by P1 clone selection, fluorescence in situ hybridization (FISH), and computer-assisted microscopy. Genomics, 1995, 26(2), 390-393.
[http://dx.doi.org/10.1016/0888-7543(95)80226-C] [PMID: 7601468]
[7]
Nakagawara, A.; Liu, X.G.; Ikegaki, N.; White, P.S.; Yamashiro, D.J.; Nycum, L.M.; Biegel, J.A.; Brodeur, G.M. Cloning and chromosomal localization of the human TRK-B tyrosine kinase receptor gene (NTRK2). Genomics, 1995, 25(2), 538-546.
[http://dx.doi.org/10.1016/0888-7543(95)80055-Q] [PMID: 7789988]
[8]
Valent, A.; Danglot, G.; Bernheim, A. Mapping of the tyrosine kinase receptors trkA (NTRK1), trkB (NTRK2) and trkC(NTRK3) to human chromosomes 1q22, 9q22 and 15q25 by fluorescence in situ hybridization. Eur. J. Hum. Genet., 1997, 5(2), 102-104.
[http://dx.doi.org/10.1159/000484742] [PMID: 9195161]
[9]
Skaper, S. The biology of neurotrophins, signalling pathways, and functional peptide mimetics of neurotrophins and their receptors. CNS Neurol. Disord. Drug Targets, 2008, 7(1), 46-62.
[http://dx.doi.org/10.2174/187152708783885174] [PMID: 18289031]
[10]
Cocco, E.; Scaltriti, M.; Drilon, A. NTRK fusion-positive cancers and TRK inhibitor therapy. Nat. Rev. Clin. Oncol., 2018, 15(12), 731-747.
[http://dx.doi.org/10.1038/s41571-018-0113-0] [PMID: 30333516]
[11]
Cunningham, M.E.; Greene, L.A. A function-structure model for NGF-activated TRK. EMBO J., 1998, 17(24), 7282-7293.
[http://dx.doi.org/10.1093/emboj/17.24.7282] [PMID: 9857185]
[12]
Amatu, A.; Sartore-Bianchi, A.; Siena, S. NTRK gene fusions as novel targets of cancer therapy across multiple tumour types. ESMO Open, 2016, 1(2), e000023.
[http://dx.doi.org/10.1136/esmoopen-2015-000023] [PMID: 27843590]
[13]
Nakagawara, A. Trk receptor tyrosine kinases: A bridge between cancer and neural development. Cancer Lett., 2001, 169(2), 107-114.
[http://dx.doi.org/10.1016/S0304-3835(01)00530-4] [PMID: 11431098]
[14]
Vaishnavi, A.; Capelletti, M.; Le, A.T.; Kako, S.; Butaney, M.; Ercan, D.; Mahale, S.; Davies, K.D.; Aisner, D.L.; Pilling, A.B.; Berge, E.M.; Kim, J.; Sasaki, H.; Park, S.; Kryukov, G.; Garraway, L.A.; Hammerman, P.S.; Haas, J.; Andrews, S.W.; Lipson, D.; Stephens, P.J.; Miller, V.A.; Varella-Garcia, M.; Jänne, P.A.; Doebele, R.C. Oncogenic and drug-sensitive NTRK1 rearrangements in lung cancer. Nat. Med., 2013, 19(11), 1469-1472.
[http://dx.doi.org/10.1038/nm.3352] [PMID: 24162815]
[15]
Ranzi, V.; Meakin, S.O.; Miranda, C.; Mondellini, P.; Pierotti, M.A.; Greco, A. The signaling adapters fibroblast growth factor receptor substrate 2 and 3 are activated by the thyroid TRK oncoproteins. Endocrinology, 2003, 144(3), 922-928.
[http://dx.doi.org/10.1210/en.2002-221002] [PMID: 12586769]
[16]
Miranda, C.; Greco, A.; Miele, C.; Pierotti, M.A.; Van Obberghen, E. IRS-1 and IRS-2 are recruited by TrkA receptor and oncogenic TRK-T1. J. Cell. Physiol., 2001, 186(1), 35-46.
[http://dx.doi.org/10.1002/1097-4652(200101)186:1<35:AID-JCP1003>3.0.CO;2-X] [PMID: 11147812]
[17]
Roccato, E.; Miranda, C.; Ranzi, V.; Gishizki, M.; Pierotti, M.A.; Greco, A. Biological activity of the thyroid TRK-T3 oncogene requires signalling through Shc. Br. J. Cancer, 2002, 87(6), 645-653.
[http://dx.doi.org/10.1038/sj.bjc.6600544] [PMID: 12237775]
[18]
Chen, Y.; Chi, P. Basket trial of TRK inhibitors demonstrates efficacy in TRK fusion-positive cancers. J. Hematol. Oncol., 2018, 11(1), 78.
[http://dx.doi.org/10.1186/s13045-018-0622-4] [PMID: 29880008]
[19]
Kummar, S.; Lassen, U.N. TRK inhibition: A new tumour-agnostic treatment strategy. Target. Oncol., 2018, 13(5), 545-556.
[http://dx.doi.org/10.1007/s11523-018-0590-1] [PMID: 30276762]
[20]
Ricciuti, B.; Brambilla, M.; Metro, G.; Baglivo, S.; Matocci, R.; Pirro, M.; Chiari, R. Targeting NTRK fusion in non-small cell lung cancer: Rationale and clinical evidence. Med. Oncol., 2017, 34(6), 105.
[http://dx.doi.org/10.1007/s12032-017-0967-5] [PMID: 28444624]
[21]
Gupta, V.; You, Y.; Gupta, V.; Klistorner, A.; Graham, S. TrkB receptor signalling: Implications in neurodegenerative, psychiatric and proliferative disorders. Int. J. Mol. Sci., 2013, 14(5), 10122-10142.
[http://dx.doi.org/10.3390/ijms140510122] [PMID: 23670594]
[22]
Tacconelli, A.; Farina, A.R.; Cappabianca, L.; Gulino, A.; Mackay, A.R. TrkAIII. A novel hypoxia-regulated alternative TrkA splice variant of potential physiological and pathological importance. Cell Cycle, 2005, 4(1), 8-9.
[http://dx.doi.org/10.4161/cc.4.1.1349] [PMID: 15611661]
[23]
Frattini, V.; Trifonov, V.; Chan, J.M.; Castano, A.; Lia, M.; Abate, F.; Keir, S.T.; Ji, A.X.; Zoppoli, P.; Niola, F.; Danussi, C.; Dolgalev, I.; Porrati, P.; Pellegatta, S.; Heguy, A.; Gupta, G.; Pisapia, D.J.; Canoll, P.; Bruce, J.N.; McLendon, R.E.; Yan, H.; Aldape, K.; Finocchiaro, G.; Mikkelsen, T.; Privé, G.G.; Bigner, D.D.; Lasorella, A.; Rabadan, R.; Iavarone, A. The integrated landscape of driver genomic alterations in glioblastoma. Nat. Genet., 2013, 45(10), 1141-1149.
[http://dx.doi.org/10.1038/ng.2734] [PMID: 23917401]
[24]
Stransky, N.; Cerami, E.; Schalm, S.; Kim, J.L.; Lengauer, C. The landscape of kinase fusions in cancer. Nat. Commun., 2014, 5(1), 4846.
[http://dx.doi.org/10.1038/ncomms5846] [PMID: 25204415]
[25]
Martin-Zanca, D.; Hughes, S.H.; Barbacid, M. A human oncogene formed by the fusion of truncated tropomyosin and protein tyrosine kinase sequences. Nature, 1986, 319(6056), 743-748.
[http://dx.doi.org/10.1038/319743a0] [PMID: 2869410]
[26]
Ardini, E.; Bosotti, R.; Borgia, A.L.; De Ponti, C.; Somaschini, A.; Cammarota, R.; Amboldi, N.; Raddrizzani, L.; Milani, A.; Magnaghi, P.; Ballinari, D.; Casero, D.; Gasparri, F.; Banfi, P.; Avanzi, N.; Saccardo, M.B.; Alzani, R.; Bandiera, T.; Felder, E.; Donati, D.; Pesenti, E.; Sartore-Bianchi, A.; Gambacorta, M.; Pierotti, M.A.; Siena, S.; Veronese, S.; Galvani, A.; Isacchi, A. The TPM3-NTRK1 rearrangement is a recurring event in colorectal carcinoma and is associated with tumor sensitivity to TRKA kinase inhibition. Mol. Oncol., 2014, 8(8), 1495-1507.
[http://dx.doi.org/10.1016/j.molonc.2014.06.001] [PMID: 24962792]
[27]
Vaishnavi, A.; Le, A.T.; Doebele, R.C. TRKing down an old oncogene in a new era of targeted therapy. Cancer Discov., 2015, 5(1), 25-34.
[http://dx.doi.org/10.1158/2159-8290.CD-14-0765] [PMID: 25527197]
[28]
Laetsch, T.W.; Hawkins, D.S. Larotrectinib for the treatment of TRK fusion solid tumors. Expert Rev. Anticancer Ther., 2019, 19(1), 1-10.
[http://dx.doi.org/10.1080/14737140.2019.1538796] [PMID: 30350734]
[29]
Gatalica, Z.; Xiu, J.; Swensen, J.; Vranic, S. Molecular characterization of cancers with NTRK gene fusions. Mod. Pathol., 2019, 32(1), 147-153.
[http://dx.doi.org/10.1038/s41379-018-0118-3] [PMID: 30171197]
[30]
Drilon, A.; Laetsch, T.W.; Kummar, S.; DuBois, S.G.; Lassen, U.N.; Demetri, G.D.; Nathenson, M.; Doebele, R.C.; Farago, A.F.; Pappo, A.S.; Turpin, B.; Dowlati, A.; Brose, M.S.; Mascarenhas, L.; Federman, N.; Berlin, J.; El-Deiry, W.S.; Baik, C.; Deeken, J.; Boni, V.; Nagasubramanian, R.; Taylor, M.; Rudzinski, E.R.; Meric-Bernstam, F.; Sohal, D.P.S.; Ma, P.C.; Raez, L.E.; Hechtman, J.F.; Benayed, R.; Ladanyi, M.; Tuch, B.B.; Ebata, K.; Cruickshank, S.; Ku, N.C.; Cox, M.C.; Hawkins, D.S.; Hong, D.S.; Hyman, D.M. Efficacy of Larotrectinib in TRK fusion-positive cancers in adults and children. N. Engl. J. Med., 2018, 378(8), 731-739.
[http://dx.doi.org/10.1056/NEJMoa1714448] [PMID: 29466156]
[31]
Hong, D.S.; DuBois, S.G.; Kummar, S.; Farago, A.F.; Albert, C.M.; Rohrberg, K.S.; van Tilburg, C.M.; Nagasubramanian, R.; Berlin, J.D.; Federman, N.; Mascarenhas, L.; Geoerger, B.; Dowlati, A.; Pappo, A.S.; Bielack, S.; Doz, F.; McDermott, R.; Patel, J.D.; Schilder, R.J.; Tahara, M.; Pfister, S.M.; Witt, O.; Ladanyi, M.; Rudzinski, E.R.; Nanda, S.; Childs, B.H.; Laetsch, T.W.; Hyman, D.M.; Drilon, A. Larotrectinib in patients with TRK fusion positive solid tumours: A pooled analysis of three phase 1/2 clinical trials. Lancet Oncol., 2020, 21(4), 531-540.
[http://dx.doi.org/10.1016/S1470-2045(19)30856-3] [PMID: 32105622]
[32]
Italiano, A.; Nanda, S.; Briggs, A.; Garcia-Foncillas, J.; Lassen, U.; Vassal, G.; Kummar, S.; van Tilburg, C.M.; Hong, D.S.; Laetsch, T.W.; Keating, K.; Reeves, J.A.; Fellous, M.; Childs, B.H.; Drilon, A.; Hyman, D.M. Larotrectinib versus prior therapies in tropomyosin receptor kinase fusion cancer: An intra-patient comparative analysis. Cancers (Basel), 2020, 12(11), 3246.
[http://dx.doi.org/10.3390/cancers12113246] [PMID: 33158040]
[33]
Federman, N.; McDermott, R. Larotrectinib, a highly selective tropomyosin receptor kinase (TRK) inhibitor for the treatment of TRK fusion cancer. Expert Rev. Clin. Pharmacol., 2019, 12(10), 931-939.
[http://dx.doi.org/10.1080/17512433.2019.1661775] [PMID: 31469968]
[34]
Scott, L.J. Larotrectinib: First global approval. Drugs, 2019, 79(2), 201-206.
[http://dx.doi.org/10.1007/s40265-018-1044-x] [PMID: 30635837]
[35]
Ghilardi, J.R.; Freeman, K.T.; Jimenez-Andrade, J.M.; Mantyh, W.G.; Bloom, A.P.; Kuskowski, M.A.; Mantyh, P.W. Administration of a tropomyosin receptor kinase inhibitor attenuates sarcomainduced nerve sprouting, neuroma formation and bone cancer pain. Mol. Pain, 2010, 6, 1744-8069-6-87.
[http://dx.doi.org/10.1186/1744-8069-6-87] [PMID: 21138586]
[36]
Doebele, R.C.; Davis, L.E.; Vaishnavi, A.; Le, A.T.; Estrada-Bernal, A.; Keysar, S.; Jimeno, A.; Varella-Garcia, M.; Aisner, D.L.; Li, Y.; Stephens, P.J.; Morosini, D.; Tuch, B.B.; Fernandes, M.; Nanda, N.; Low, J.A. An oncogenic NTRK fusion in a patient with soft-tissue sarcoma with response to the tropomyosin-related kinase inhibitor LOXO-101. Cancer Discov., 2015, 5(10), 1049-1057.
[http://dx.doi.org/10.1158/2159-8290.CD-15-0443] [PMID: 26216294]
[37]
BayerA phase 2 basket study of the oral TRK inhibitor larotrectinib in subjects with NTRK fusion-positive tumors, 2023-via ClinicalTrials.gov (NCT02576431). 2023.
[38]
Rozlytrek. 2020. Available From: https://www.tga.gov.au/resources/auspmd/rozlytrek
[39]
Rozlytrek. 2020. Available From: https://www.ema.europa.eu/en/medicines/human/EPAR/rozlytrek
[40]
Genentech. FDA Approves Genentech's Rozlytrek (entrectinib) for People With ROS1-Positive, Metastatic Non-Small Cell Lung Cancer and NTRK Gene Fusion-Positive Solid Tumors 2019. Available From: https://www.gene.com/media/press-releases/14802/2019-08-15/fda-approves-genentechs-rozlytrek-entrec
[41]
Iyer, R.; Wehrmann, L.; Golden, R.L.; Naraparaju, K.; Croucher, J.L.; MacFarland, S.P.; Guan, P.; Kolla, V.; Wei, G.; Cam, N.; Li, G.; Hornby, Z.; Brodeur, G.M. Entrectinib is a potent inhibitor of Trk-driven neuroblastomas in a xenograft mouse model. Cancer Lett., 2016, 372(2), 179-186.
[http://dx.doi.org/10.1016/j.canlet.2016.01.018] [PMID: 26797418]
[42]
Ardini, E.; Menichincheri, M.; Banfi, P.; Bosotti, R.; De Ponti, C.; Pulci, R.; Ballinari, D.; Ciomei, M.; Texido, G.; Degrassi, A.; Avanzi, N.; Amboldi, N.; Saccardo, M.B.; Casero, D.; Orsini, P.; Bandiera, T.; Mologni, L.; Anderson, D.; Wei, G.; Harris, J.; Vernier, J.M.; Li, G.; Felder, E.; Donati, D.; Isacchi, A.; Pesenti, E.; Magnaghi, P.; Galvani, A. Entrectinib, a Pan-TRK, ROS1, and ALK Inhibitor with Activity in Multiple Molecularly Defined Cancer Indications. Mol. Cancer Ther., 2016, 15(4), 628-639.
[http://dx.doi.org/10.1158/1535-7163.MCT-15-0758] [PMID: 26939704]
[43]
Drilon, A.; Braud, F.G.; Siena, S.; Ou, S.H.; Patel, M.; Ahn, M.J.; Lee, J.; Bauer, T.M.; Farago, A.F.; Liu, S.V.; Reddinger, N.; Patel, R.; Luo, D.; Maneval, E.C.; Multani, P.S.; Doebele, R.C.; Shaw, A.T. Entrectinib, an oral pan-Trk, ROS1, and ALK inhibitor in TKI-naive patients with advanced solid tumors harboring gene rearrangements-updated phase 1 results. Abstract number CT007. Cancer Res., 2016, 76(14 Supplement), CT007.
[http://dx.doi.org/10.1158/1538-7445.AM2016-CT007]
[44]
Siena, S.; Drilon, A.E.; Sai-Hong ou, I. Farago, A.F.; Patel, M.; Bauer, T.M.; Hong, D.; Liu, S.V.; Lee, J.; Patel, R.; Schechet, L.; Luo, D.; Chow Maneval, E.; Multani, P.S.; De Braud, F.G. 29LBA Entrectinib (RXDX-101), an oral pan-Trk, ROS1, and ALK inhibitor in patients with advanced solid tumors harboring gene rearrangements. Eur. J. Cancer, 2015, 51, S724-S725.
[http://dx.doi.org/10.1016/S0959-8049(16)31947-5]
[45]
Ardini, E.; Siena, S. Entrectinib approval by EMA reinforces options for ROS1 and tumour agnostic NTRK targeted cancer therapies. ESMO Open, 2020, 5(5), e000867.
[http://dx.doi.org/10.1136/esmoopen-2020-000867] [PMID: 32907817]
[46]
Hoffmann-La, R. Basket study of Entrectinib (RXDX-101) for the treatment of patients with solid tumors harboring NTRK 1/2/3 (Trk A/B/C), ROS1, or ALK gene rearrangements (fusions) (STARTRK-2). 2023. Available From: https://www.cancer.gov/research/participate/clinical-trials-search/v?id=NCT02568267&r=1
[47]
Drilon, A.; Ou, S.H.I.; Cho, B.C.; Kim, D.W.; Lee, J.; Lin, J.J.; Zhu, V.W.; Ahn, M.J.; Camidge, D.R.; Nguyen, J.; Zhai, D.; Deng, W.; Huang, Z.; Rogers, E.; Liu, J.; Whitten, J.; Lim, J.K.; Stopatschinskaja, S.; Hyman, D.M.; Doebele, R.C.; Cui, J.J.; Shaw, A.T. Repotrectinib (TPX-0005) is a next-generation ROS1/TRK/ALK inhibitor that potently inhibits ROS1/TRK/ALK solvent-front mutations. Cancer Discov., 2018, 8(10), 1227-1236.
[http://dx.doi.org/10.1158/2159-8290.CD-18-0484] [PMID: 30093503]
[48]
Yun, M.R.; Kim, D.H.; Kim, S.Y.; Joo, H.S.; Lee, Y.W.; Choi, H.M.; Park, C.W.; Heo, S.G.; Kang, H.N.; Lee, S.S.; Schoenfeld, A.J.; Drilon, A.; Kang, S.G.; Shim, H.S.; Hong, M.H.; Cui, J.J.; Kim, H.R.; Cho, B.C. Repotrectinib exhibits potent antitumor activity in treatment-naive and solvent-front-mutant ROS1-rearranged non-small cell lung cancer. Clin. Cancer Res., 2020, 26(13), 3287-3295.
[http://dx.doi.org/10.1158/1078-0432.CCR-19-2777] [PMID: 32269053]
[49]
Deng, W.; Zhai, D.; Zhang, X.; Lee, D.; Rogers, E.; Whitten, J.; Cui, J.J. Repotrectinib, a new generation ROS1 inhibitor, is highly potent against fusion ros1s and emerging resistance mutations. Abstract Number 1319. Cancer Res., 2019, 79(13)(Suppl.)
[50]
Cervantes-Madrid, D.; Szydzik, J.; Lind, D.E.; Borenäs, M.; Bemark, M.; Cui, J.; Palmer, R.H.; Hallberg, B. Repotrectinib (TPX-0005), effectively reduces growth of ALK driven neuroblastoma cells. Sci. Rep., 2019, 9(1), 19353.
[http://dx.doi.org/10.1038/s41598-019-55060-7] [PMID: 31852910]
[51]
Wu, P.; Nielsen, T.E.; Clausen, M.H. FDA-approved small-molecule kinase inhibitors. Trends Pharmacol. Sci., 2015, 36(7), 422-439.
[http://dx.doi.org/10.1016/j.tips.2015.04.005] [PMID: 25975227]
[52]
Su, H.P.; Rickert, K.; Burlein, C.; Narayan, K.; Bukhtiyarova, M.; Hurzy, D.M.; Stump, C.A.; Zhang, X.; Reid, J.; Krasowska-Zoladek, A.; Tummala, S.; Shipman, J.M.; Kornienko, M.; Lemaire, P.A.; Krosky, D.; Heller, A.; Achab, A.; Chamberlin, C.; Saradjian, P.; Sauvagnat, B.; Yang, X.; Ziebell, M.R.; Nickbarg, E.; Sanders, J.M.; Bilodeau, M.T.; Carroll, S.S.; Lumb, K.J.; Soisson, S.M.; Henze, D.A.; Cooke, A.J. Structural characterization of nonactive site, TrkA-selective kinase inhibitors. Proc. Natl. Acad. Sci. USA, 2017, 114(3), E297-E306.
[http://dx.doi.org/10.1073/pnas.1611577114] [PMID: 28039433]
[53]
Escudier, B.; Eisen, T.; Stadler, W.M.; Szczylik, C.; Oudard, S.; Siebels, M.; Negrier, S.; Chevreau, C.; Solska, E.; Desai, A.A.; Rolland, F.; Demkow, T.; Hutson, T.E.; Gore, M.; Freeman, S.; Schwartz, B.; Shan, M.; Simantov, R.; Bukowski, R.M. Sorafenib in advanced clear-cell renal-cell carcinoma. N. Engl. J. Med., 2007, 356(2), 125-134.
[http://dx.doi.org/10.1056/NEJMoa060655] [PMID: 17215530]
[54]
Mousa, A.B. Sorafenib in the treatment of advanced hepatocellular carcinoma. Saudi J. Gastroenterol., 2008, 14(1), 40-42.
[http://dx.doi.org/10.4103/1319-3767.37808] [PMID: 19568496]
[55]
Bruix, J.; Raoul, J.L.; Sherman, M.; Mazzaferro, V.; Bolondi, L.; Craxi, A.; Galle, P.R.; Santoro, A.; Beaugrand, M.; Sangiovanni, A.; Porta, C.; Gerken, G.; Marrero, J.A.; Nadel, A.; Shan, M.; Moscovici, M.; Voliotis, D.; Llovet, J.M. Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma: Subanalyses of a phase III trial. J. Hepatol., 2012, 57(4), 821-829.
[http://dx.doi.org/10.1016/j.jhep.2012.06.014] [PMID: 22727733]
[56]
Raoul, J.L.; Adhoute, X.; Penaranda, G.; Perrier, H.; Castellani, P.; Oules, V.; Bourlière, M. Sorafenib: Experience and better management of side effects improve overall survival in hepatocellular carcinoma patients: A real-life retrospective analysis. Liver Cancer, 2019, 8(6), 457-467.
[http://dx.doi.org/10.1159/000497161] [PMID: 31799203]
[57]
Gandin, V.; Ferrarese, A.; Dalla Via, M.; Marzano, C.; Chilin, A.; Marzaro, G. Targeting kinases with anilinopyrimidines: Discovery of N-phenyl-N’-[4-(pyrimidin-4-ylamino)phenyl]urea derivatives as selective inhibitors of class III receptor tyrosine kinase subfamily. Sci. Rep., 2015, 5(1), 16750.
[http://dx.doi.org/10.1038/srep16750] [PMID: 26568452]
[58]
Abou-Alfa, G.K.; Meyer, T.; Cheng, A.L.; El-Khoueiry, A.B.; Rimassa, L.; Ryoo, B.Y.; Cicin, I.; Merle, P.; Chen, Y.; Park, J.W.; Blanc, J.F.; Bolondi, L.; Klümpen, H.J.; Chan, S.L.; Zagonel, V.; Pressiani, T.; Ryu, M.H.; Venook, A.P.; Hessel, C.; Borgman-Hagey, A.E.; Schwab, G.; Kelley, R.K. Cabozantinib in patients with advanced and progressing hepatocellular carcinoma. N. Engl. J. Med., 2018, 379(1), 54-63.
[http://dx.doi.org/10.1056/NEJMoa1717002] [PMID: 29972759]
[59]
Kelley, R.K.; Miksad, R.; Cicin, I.; Chen, Y.; Klümpen, H.J.; Kim, S.; Lin, Z.Z.; Youkstetter, J.; Hazra, S.; Sen, S.; Cheng, A.L.; El-Khoueiry, A.B.; Meyer, T.; Abou-Alfa, G.K. Efficacy and safety of cabozantinib for patients with advanced hepatocellular carcinoma based on albumin-bilirubin grade. Br. J. Cancer, 2022, 126(4), 569-575.
[http://dx.doi.org/10.1038/s41416-021-01532-5] [PMID: 34621044]
[60]
Abou-Alfa, G.K.; Borgman-Hagey, A.E.; Kelley, R.K. Cabozantinib in hepatocellular carcinoma. N. Engl. J. Med., 2018, 379(14), 1384-1385.
[http://dx.doi.org/10.1056/NEJMc1810178] [PMID: 30281991]
[61]
Allaire, M.; Nault, J.C. Cabozantinib and the moving field of systemic treatments in advanced hepatocellular carcinoma. Hepatobiliary Surg. Nutr., 2019, 8(1), 53-55.
[http://dx.doi.org/10.21037/hbsn.2018.10.12] [PMID: 30881965]
[62]
Trojan, J. Cabozantinib for the treatment of advanced hepatocellular carcinoma: Current data and future perspectives. Drugs, 2020, 80(12), 1203-1210.
[http://dx.doi.org/10.1007/s40265-020-01361-5] [PMID: 32671719]
[63]
Nix, N.M.; Braun, K. Cabozantinib for the treatment of metastatic medullary thyroid carcinoma. J. Adv. Pract. Oncol., 2014, 5(1), 47-50.
[PMID: 25032033]
[64]
U.S. Food And Drug Administration. FFDA approves cabozantinib for differentiated thyroid cancer. 2021. Available From: https://www.fda.gov/drugs/resources-information-approveddrugs/fda-approves-cabozantinib-differentiated-thyroid-cancer
[65]
Ma, X.; Shen, L.; Zhang, J.; Liu, G.; Zhan, S.; Ding, B.; Lv, X. Novel 4-acrylamido-quinoline derivatives as potent PI3K/mTOR dual inhibitors: The design, synthesis, and in vitro and in vivo biological evaluation. Front Chem., 2019, 7, 236.
[http://dx.doi.org/10.3389/fchem.2019.00236] [PMID: 31069214]
[66]
Hong, S.; Kim, J.; Seo, J.H.; Jung, K.H.; Hong, S.S.; Hong, S. Design, synthesis, and evaluation of 3,5-disubstituted 7-azaindoles as Trk inhibitors with anticancer and antiangiogenic activities. J. Med. Chem., 2012, 55(11), 5337-5349.
[http://dx.doi.org/10.1021/jm3002982] [PMID: 22575050]
[67]
Zhao, X.; Huang, W.; Wang, Y.; Xin, M.; Jin, Q.; Cai, J.; Tang, F.; Zhao, Y.; Xiang, H. Pyrrolo[2,3-b]pyridine derivatives as potent Bruton’s tyrosine kinase inhibitors. Bioorg. Med. Chem., 2015, 23(15), 4344-4353.
[http://dx.doi.org/10.1016/j.bmc.2015.06.023] [PMID: 26169764]
[68]
Ibrahim, P.N.; Artis, D.R.; Bremer, R.; Habets, G.; Mamo, S.; Nespi, M.; Zhang, C.; Zhang, J.; Zhu, Y.L.; Zuckerman, R.; West, B.; Suzuki, Y.; Tsai, J.; Hirth, K.P.; Bollag, G.; Gillette, J.; Wu, G.; Zhu, H.; Shi, S. Pyrrolo[2,3-b] pyridine derivatives as protein kinase inhibitors WO2007002325, 2007.
[69]
Salom, B.; D’Anello, M.; Brasca, M.G.; Giordano, P.; Martina, K.; Angelucci, F.; Brookfield, F.A.; Trigg, W.J.; Boyd, E.A.; Larard, J.A. Pyrrolo[2,3-b]pyridine derivatives active as kinase inhibitors and pharmaceutical compositions comprising them. US8106069B2, 2012.
[70]
Liu, N.; Wang, X.; Fu, Q.; Qin, Q.; Wu, T.; Lv, R.; Zhao, D.; Cheng, M. Design, synthesis and biological evaluation of pyrazolo[3,4- b]pyridine derivatives as TRK inhibitors. RSC Medicinal Chemistry, 2023, 14(1), 85-102.
[http://dx.doi.org/10.1039/D2MD00334A] [PMID: 36760745]
[71]
Zhang, Y.; Liu, Y.; Zhou, Y.; Zhang, Q.; Han, T.; Tang, C.; Fan, W. Pyrazolo[1,5-a]pyrimidine based Trk inhibitors: Design, synthesis, biological activity evaluation. Bioorg. Med. Chem. Lett., 2021, 31, 127712.
[http://dx.doi.org/10.1016/j.bmcl.2020.127712] [PMID: 33246108]
[72]
Yuliya, K.; Endryusyuytun, U.; Tszyangan, C. Substituted pyrazolo[1,5-A] pyrimidine compounds as Trk kinase inhibitors. RU2018131134A, 2008.
[73]
Allen, S.; Andrews, S.S.; Condroski, K.R.; Haas, J.; Huang, L.; Jiang, Y.; Kercher, T.; Seo, J. Substituted pyrazolo[1,5-a]pyrimidine compounds as TRK kinase inhibitors. WO2011006074A1, 2011.
[74]
Haas, J.; Andrews, S.W.; Jiang, Y.; Zhang, G. Substituted pyrazolo[1,5-a]pyrimidine compounds as TRK kinase inhibitors. US8513263B2, 2013.
[75]
Gong, Y.; Wu, F.X.; Wang, M.S.; Xu, H.C.; Zhuo, L.S.; Yang, G.F.; Huang, W. Discovery of 3-pyrazolyl-substituted pyrazolo[1,5-a]pyrimidine derivatives as potent TRK inhibitors to overcome clinically acquired resistance. Eur. J. Med. Chem., 2022, 241, 114654.
[http://dx.doi.org/10.1016/j.ejmech.2022.114654] [PMID: 35961071]
[76]
Cui, S.; Wang, Y.; Wang, Y.; Tang, X.; Ren, X.; Zhang, L.; Xu, Y.; Zhang, Z.; Zhang, Z.M.; Lu, X.; Ding, K. Design, synthesis and biological evaluation of 3-(imidazo[1,2-a]pyrazin-3-ylethynyl)-2-methylbenzamides as potent and selective pan-tropomyosin receptor kinase (TRK) inhibitors. Eur. J. Med. Chem., 2019, 179, 470-482.
[http://dx.doi.org/10.1016/j.ejmech.2019.06.064] [PMID: 31271959]
[77]
Sun, M.; Cai, S.; Li, P.; Zhang, F.; Zhang, H.; Zhou, J. Design, synthesis and biological activity of bicyclic carboxamide derivatives as TRK inhibitors. Bioorg. Med. Chem., 2020, 28(23), 115811.
[http://dx.doi.org/10.1016/j.bmc.2020.115811] [PMID: 33069129]
[78]
Frett, B.; McConnell, N.; Wang, Y.; Xu, Z.; Ambrose, A.; Li, H. Identification of pyrazine-based TrkA inhibitors: Design, synthesis, evaluation, and computational modeling studies. MedChemComm, 2014, 5(10), 1507-1514.
[http://dx.doi.org/10.1039/C4MD00251B] [PMID: 26843921]
[79]
Guo, J.; Xiang, S.; Wang, J.; Zhou, Y.; Wang, Z.; Zhang, Z.; Ding, K.; Lu, X. Discovery of novel TrkA allosteric inhibitors: Structure-based virtual screening, biological evaluation and preliminary SAR studies. Eur. J. Med. Chem., 2022, 228, 114022.
[http://dx.doi.org/10.1016/j.ejmech.2021.114022] [PMID: 34871843]
[80]
Thress, K.; MacIntyre, T.; Wang, H.; Whitston, D.; Liu, Z.Y.; Hoffmann, E.; Wang, T.; Brown, J.L.; Webster, K.; Omer, C.; Zage, P.E.; Zeng, L.; Zweidler-McKay, P.A. Identification and preclinical characterization of AZ-23, a novel, selective, and orally bioavailable inhibitor of the Trk kinase pathway. Mol. Cancer Ther., 2009, 8(7), 1818-1827.
[http://dx.doi.org/10.1158/1535-7163.MCT-09-0036] [PMID: 19509272]
[81]
Tao, X.X.; Duan, Y.T.; Chen, L.W.; Tang, D.J.; Yang, M.R.; Wang, P.F.; Xu, C.; Zhu, H.L. Design, synthesis and biological evaluation of pyrazolyl-nitroimidazole derivatives as potential EGFR/HER-2 kinase inhibitors. Bioorg. Med. Chem. Lett., 2016, 26(2), 677-683.
[http://dx.doi.org/10.1016/j.bmcl.2015.11.040] [PMID: 26652482]
[82]
Wang, T.; Lamb, M.L.; Scott, D.A.; Wang, H.; Block, M.H.; Lyne, P.D.; Lee, J.W.; Davies, A.M.; Zhang, H.J.; Zhu, Y.; Gu, F.; Han, Y.; Wang, B.; Mohr, P.J.; Kaus, R.J.; Josey, J.A.; Hoffmann, E.; Thress, K.; MacIntyre, T.; Wang, H.; Omer, C.A.; Yu, D. Identification of 4-aminopyrazolylpyrimidines as potent inhibitors of Trk kinases. J. Med. Chem., 2008, 51(15), 4672-4684.
[http://dx.doi.org/10.1021/jm800343j] [PMID: 18646745]
[83]
Malik, M.S.; Alsantali, R.I.; Jamal, Q.M.S.; Seddigi, Z.S.; Morad, M.; Alsharif, M.A.; Hussein, E.M.; Jassas, R.S.; Al-Rooqi, M.M.; Abduljaleel, Z.; Babalgith, A.O.; Altass, H.M.; Moussa, Z.; Ahmed, S.A. New imidazole-based N-phenylbenzamide derivatives as potential anticancer agents: Key computational insights. Front Chem., 2022, 9, 808556.
[http://dx.doi.org/10.3389/fchem.2021.808556] [PMID: 35155379]
[84]
Aouidate, A.; Ghaleb, A.; Ghamali, M.; Chtita, S.; Ousaa, A.; Choukrad, M.; Sbai, A.; Bouachrine, M.; Lakhlifi, T. Molecular docking and 3D-QSAR studies on 7-azaindole derivatives as inhibitors of Trk A: A strategic design in novel anticancer agents. Lett. Drug Des. Discov., 2018, 15(11), 1211-1223.
[http://dx.doi.org/10.2174/1570180815666171229151138]
[85]
Zhang, L.; Deng, X.S.; Meng, G.P.; Zhang, C.; Liu, C.C.; Chen, G.Z.; Jiang, X.L.; Zhao, Q.C.; Hu, C. Design, Synthesis and biological evaluation of a novel series of indole-3-carboxamide derivatives for cancer treatment as EGFR inhibitors. Lett. Drug Des. Discov., 2018, 15(1), 70-83.
[http://dx.doi.org/10.2174/1570180814666170929093258]
[86]
Scott, L.J. Osimertinib as first-line therapy in advanced NSCLC: A profile of its use. Drugs Ther. Perspect., 2018, 34(8), 351-357.
[http://dx.doi.org/10.1007/s40267-018-0536-9] [PMID: 30631243]
[87]
Ramalingam, S.S.; Vansteenkiste, J.; Planchard, D.; Cho, B.C.; Gray, J.E.; Ohe, Y.; Zhou, C.; Reungwetwattana, T.; Cheng, Y.; Chewaskulyong, B.; Shah, R.; Cobo, M.; Lee, K.H.; Cheema, P.; Tiseo, M.; John, T.; Lin, M.C.; Imamura, F.; Kurata, T.; Todd, A.; Hodge, R.; Saggese, M.; Rukazenkov, Y.; Soria, J.C. Overall survival with osimertinib in untreated, EGFR-mutated advanced NSCLC. N. Engl. J. Med., 2020, 382(1), 41-50.
[http://dx.doi.org/10.1056/NEJMoa1913662] [PMID: 31751012]
[88]
Zhou, P.; Chen, G.; Gao, M.; Wu, J. Design, synthesis and evaluation of the osimertinib analogue (C-005) as potent EGFR inhibitor against NSCLC. Bioorg. Med. Chem., 2018, 26(23-24), 6135-6145.
[http://dx.doi.org/10.1016/j.bmc.2018.10.018] [PMID: 30442506]
[89]
Soria, J.C.; Ohe, Y.; Vansteenkiste, J.; Reungwetwattana, T.; Chewaskulyong, B.; Lee, K.H.; Dechaphunkul, A.; Imamura, F.; Nogami, N.; Kurata, T.; Okamoto, I.; Zhou, C.; Cho, B.C.; Cheng, Y.; Cho, E.K.; Voon, P.J.; Planchard, D.; Su, W.C.; Gray, J.E.; Lee, S.M.; Hodge, R.; Marotti, M.; Rukazenkov, Y.; Ramalingam, S.S. FLAURA Investigators. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N. Engl. J. Med., 2018, 378(2), 113-125.
[http://dx.doi.org/10.1056/NEJMoa1713137] [PMID: 29151359]
[90]
Albaugh, P.; Fan, Y.; Mi, Y.; Sun, F.; Adrian, F.; Li, N.; Jia, Y.; Sarkisova, Y.; Kreusch, A.; Hood, T.; Lu, M.; Liu, G.; Huang, S.; Liu, Z.; Loren, J.; Tuntland, T.; Karanewsky, D.S.; Seidel, H.M.; Molteni, V. Discovery of GNF-5837, a selective TRK inhibitor with efficacy in rodent cancer tumor models. ACS Med. Chem. Lett., 2012, 3(2), 140-145.
[http://dx.doi.org/10.1021/ml200261d] [PMID: 24900443]
[91]
Le Tourneau, C.; Raymond, E.; Faivre, S. Sunitinib: A novel tyrosine kinase inhibitor. A brief review of its therapeutic potential in the treatment of renal carcinoma and gastrointestinal stromal tumors (GIST). Ther. Clin. Risk Manag., 2007, 3(2), 341-348.
[http://dx.doi.org/10.2147/tcrm.2007.3.2.341] [PMID: 18360643]
[92]
Li, J.; Ren, H.Y.; Zhang, J.; Dong, P.; Wang, Y.; Stevens, A.L.; Han, Y.; Huang, M. Cost-effectiveness of sunitinib as a second-line treatment for gastrointestinal stromal tumor in the People’s Republic of China. Comp. Eff. Res, 2017, 7, 1-9.
[93]
Yan, W.; Zhang, L.; Lv, F.; Moccia, M.; Carlomagno, F.; Landry, C.; Santoro, M.; Gosselet, F.; Frett, B.; Li, H. Discovery of pyrazolo-thieno[3,2-d]pyrimidinylamino-phenyl acetamides as type-II pan-tropomyosin receptor kinase (TRK) inhibitors: Design, synthesis, and biological evaluation. Eur. J. Med. Chem., 2021, 216, 113265.
[http://dx.doi.org/10.1016/j.ejmech.2021.113265] [PMID: 33652352]
[94]
Wu, T.; Zhang, C.; Lv, R.; Qin, Q.; Liu, N.; Yin, W.; Wang, R.; Sun, Y.; Wang, X.; Sun, Y.; Zhao, D.; Cheng, M. Design, synthesis, biological evaluation and pharmacophore model analysis of novel tetrahydropyrrolo[3,4-c]pyrazol derivatives as potential TRKs inhibitors. Eur. J. Med. Chem., 2021, 223, 113627.
[http://dx.doi.org/10.1016/j.ejmech.2021.113627] [PMID: 34171657]
[95]
Li, P.; Cai, S.; Zhao, T.; Xu, L.; Guan, D.; Li, J.; Zhou, J.; Zhang, H. Design, synthesis and biological evaluation of macrocyclic derivatives as TRK inhibitors. Bioorg. Med. Chem. Lett., 2021, 53, 128409.
[http://dx.doi.org/10.1016/j.bmcl.2021.128409] [PMID: 34628036]
[96]
Kim, M.H.; Tsuhako, A.L.; Co, E.W.; Aftab, D.T.; Bentzien, F.; Chen, J.; Cheng, W.; Engst, S.; Goon, L.; Klein, R.R.; Le, D.T.; Mac, M.; Parks, J.J.; Qian, F.; Rodriquez, M.; Stout, T.J.; Till, J.H.; Won, K.A.; Wu, X.; Michael Yakes, F.; Yu, P.; Zhang, W.; Zhao, Y.; Lamb, P.; Nuss, J.M.; Xu, W. The design, synthesis, and biological evaluation of potent receptor tyrosine kinase inhibitors. Bioorg. Med. Chem. Lett., 2012, 22(15), 4979-4985.
[http://dx.doi.org/10.1016/j.bmcl.2012.06.029] [PMID: 22765894]
[97]
Ma, F.; Liu, P.; Lei, M.; Liu, J.; Wang, H.; Zhao, S.; Hu, L. Design, synthesis and biological evaluation of indolin-2-one-based derivatives as potent, selective and efficacious inhibitors of FMS-like tyrosine kinase3 (FLT3). Eur. J. Med. Chem., 2017, 127, 72-86.
[http://dx.doi.org/10.1016/j.ejmech.2016.12.038] [PMID: 28038328]
[98]
Sever, B.; Altintop, M.D.; Radwan, M.O.; Özdemir, A.; Otsuka, M.; Fujita, M.; Ciftci, H.I. Design, synthesis and biological evaluation of a new series of thiazolyl-pyrazolines as dual EGFR and HER2 inhibitors. Eur. J. Med. Chem., 2019, 182, 111648.
[http://dx.doi.org/10.1016/j.ejmech.2019.111648] [PMID: 31493743]
[99]
Qiu, K.M.; Wang, H.H.; Wang, L.M.; Luo, Y.; Yang, X.H.; Wang, X.M.; Zhu, H.L. Design, synthesis and biological evaluation of pyrazolyl-thiazolinone derivatives as potential EGFR and HER-2 kinase inhibitors. Bioorg. Med. Chem., 2012, 20(6), 2010-2018.
[http://dx.doi.org/10.1016/j.bmc.2012.01.051] [PMID: 22361272]
[100]
Xie, Z.; Cheng, D.; Luo, L.; Shen, G.; Pan, S.; Pan, Y.; Chen, B.; Wang, X.; Liu, Z.; Zhang, Y.; Ye, F. Design, synthesis and biological evaluation of 4-bromo-N-(3,5-dimethoxyphenyl)benzamide derivatives as novel FGFR1 inhibitors for treatment of non-small cell lung cancer. J. Enzyme Inhib. Med. Chem., 2018, 33(1), 905-919.
[http://dx.doi.org/10.1080/14756366.2018.1460824] [PMID: 29734851]
[101]
Kalinichenko, E.; Faryna, A.; Bozhok, T.; Panibrat, A. Synthesis, in vitro and in silico anticancer activity of new 4-methylbenzamide derivatives containing 2,6-substituted purines as potential protein kinases inhibitors. Int. J. Mol. Sci., 2021, 22(23), 12738.
[http://dx.doi.org/10.3390/ijms222312738] [PMID: 34884546]
[102]
Chen, X.; Liu, Y.; Zhang, L.; Chen, D.; Dong, Z.; Zhao, C.; Liu, Z.; Xia, Q.; Wu, J.; Chen, Y.; Zheng, X.; Cai, Y. Design, synthesis, and biological evaluation of indazole derivatives as selective and potent FGFR4 inhibitors for the treatment of FGF19-driven hepatocellular cancer. Eur. J. Med. Chem., 2021, 214, 113219.
[http://dx.doi.org/10.1016/j.ejmech.2021.113219] [PMID: 33618175]
[103]
Elsayed, N.M.Y.; Abou El Ella, D.A.; Serya, R.A.T.; Tolba, M.F.; Shalaby, R.; Abouzid, K.A.M. Design, synthesis and biological evaluation of indazole-pyrimidine based derivatives as anticancer agents with anti-angiogenic and antiproliferative activities. MedChemComm, 2016, 7(5), 881-899.
[http://dx.doi.org/10.1039/C5MD00602C]
[104]
Wei, W.; Liu, Z.; Wu, X.; Gan, C.; Su, X.; Liu, H.; Que, H.; Zhang, Q.; Xue, Q.; Yue, L.; Yu, L.; Ye, T. Synthesis and biological evaluation of indazole derivatives as anti-cancer agents. RSC Advances, 2021, 11(26), 15675-15687.
[http://dx.doi.org/10.1039/D1RA01147B] [PMID: 35481216]
[105]
Shirahashi, H.; Toriihara, E.; Suenaga, Y.; Yoshida, H.; Akaogi, K.; Endou, Y.; Wakabayashi, M.; Takashima, M. The discovery of novel 3-aryl-indazole derivatives as peripherally restricted pan-Trk inhibitors for the treatment of pain. Bioorg. Med. Chem. Lett., 2019, 29(16), 2320-2326.
[http://dx.doi.org/10.1016/j.bmcl.2019.06.018] [PMID: 31235262]
[106]
Jia, Y.; Zhang, J.; Feng, J.; Xu, F.; Pan, H.; Xu, W. Design, synthesis and biological evaluation of pazopanib derivatives as antitumor agents. Chem. Biol. Drug Des., 2014, 83(3), 306-316.
[http://dx.doi.org/10.1111/cbdd.12243] [PMID: 24119291]
[107]
Pragathi, Y.J.; Sreenivasulu, R.; Veronica, D.; Raju, R.R. Design, synthesis, and biological evaluation of 1,2,4-thiadiazole-1,2,4-triazole derivatives bearing amide functionality as anticancer agents. Arab. J. Sci. Eng., 2021, 46(1), 225-232.
[http://dx.doi.org/10.1007/s13369-020-04626-z] [PMID: 32837812]
[108]
Wang, X.; Tan, Z.; Wang, F.; Zhang, J.; Yang, J.; Liu, S.; Jiang, N.; Zhai, X. Design, synthesis and anti-tumor efficacy of novel phenyl thiazole/triazole derivatives as selective TrkA inhibitors. Bioorg. Med. Chem., 2022, 72, 116995.
[http://dx.doi.org/10.1016/j.bmc.2022.116995] [PMID: 36095945]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy