Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Developments of Fms-like Tyrosine Kinase 3 Inhibitors as Anticancer Agents for AML Treatment

Author(s): Chenchen Ma, Siyuan Cui* and Ruirong Xu*

Volume 31, Issue 29, 2024

Published on: 09 January, 2024

Page: [4657 - 4686] Pages: 30

DOI: 10.2174/0109298673277543231205072556

Price: $65

Abstract

Background: FMS-like tyrosine kinase 3 (FLT3) is a commonly mutated gene in acute myeloid leukemia. As a receptor tyrosine kinase (RTK), FLT3 plays a role in the proliferation and differentiation of hematopoietic stem cells. As the most frequent molecular alteration in AML, FLT3 has drawn the attention of many researchers, and a lot of small molecule inhibitors targeting FLT3 have been intensively investigated as potential drugs for AML therapy.

Methods: In this paper, PubMed and SciFinder® were used as a tool; the publications about “FLT3 inhibitor” and “Acute myeloid leukemia” were surveyed from 2014 to the present with an exclusion of those published as patents.

Results: In this study, the structural characterization and biological activities of representative FLT3 inhibitors were summarized. The major challenges and future directions for further research are discussed.

Conclusion: Recently, numerous FLT3 inhibitors have been discovered and employed in FLT3-mutated AML treatment. In order to overcome the drug resistance caused by FLT3 mutations, screening multitargets FLT3 inhibitors has become the main research direction. In addition, the emergence of irreversible FLT3 inhibitors also provides new ideas for discovering new FLT3 inhibitors.

[1]
Chung, H.J.; Kamli, M.R.; Lee, H.J.; Ha, J.D.; Cho, S.Y.; Lee, J.; Kong, J.Y.; Han, S.Y. Discovery of quinolinone derivatives as potent FLT3 inhibitors. Biochem. Biophys. Res. Commun., 2014, 445(3), 561-565.
[http://dx.doi.org/10.1016/j.bbrc.2014.02.029] [PMID: 24530392]
[2]
Short, N.J.; Rytting, M.E.; Cortes, J.E. Acute myeloid leukaemia. Lancet, 2018, 392(10147), 593-606.
[http://dx.doi.org/10.1016/S0140-6736(18)31041-9] [PMID: 30078459]
[3]
De Kouchkovsky, I.; Abdul-Hay, M. Acute myeloid leukemia: A comprehensive review and 2016 update. Blood Cancer J., 2016, 6(7), e441.
[http://dx.doi.org/10.1038/bcj.2016.50] [PMID: 27367478]
[4]
Rowe, J.M. Changing trends in the therapy of acute myeloid leukemia. Best Pract. Res. Clin. Haematol., 2021, 34(4), 101333.
[http://dx.doi.org/10.1016/j.beha.2021.101333] [PMID: 34865705]
[5]
Molica, M.; Mazzone, C.; Niscola, P.; Carmosino, I.; Di Veroli, A.; De Gregoris, C.; Bonanni, F.; Perrone, S.; Cenfra, N.; Fianchi, L.; Piccioni, A.L.; Spadea, A.; Luzi, G.; Mengarelli, A.; Cudillo, L.; Maurillo, L.; Pagano, L.; Breccia, M.; Rigacci, L.; De Fabritiis, P. Identification of predictive factors for overall survival and response during hypomethylating treatment in very elderly (≥75 Years) acute myeloid leukemia patients: A multicenter real-life experience. Cancers, 2022, 14(19), 4897.
[http://dx.doi.org/10.3390/cancers14194897] [PMID: 36230820]
[6]
Fedorov, K.; Maiti, A.; Konopleva, M. Targeting FLT3 mutation in acute myeloid leukemia: Current strategies and future directions. Cancers, 2023, 15(8), 2312.
[http://dx.doi.org/10.3390/cancers15082312] [PMID: 37190240]
[7]
Elgarten, C.W.; Aplenc, R. Pediatric acute myeloid leukemia: Updates on biology, risk stratification, and therapy. Curr. Opin. Pediatr., 2020, 32(1), 57-66.
[http://dx.doi.org/10.1097/MOP.0000000000000855] [PMID: 31815781]
[8]
Papaemmanuil, E.; Gerstung, M.; Bullinger, L.; Gaidzik, V.I.; Paschka, P.; Roberts, N.D.; Potter, N.E.; Heuser, M.; Thol, F.; Bolli, N.; Gundem, G.; Van Loo, P.; Martincorena, I.; Ganly, P.; Mudie, L.; McLaren, S.; O’Meara, S.; Raine, K.; Jones, D.R.; Teague, J.W.; Butler, A.P.; Greaves, M.F.; Ganser, A.; Döhner, K.; Schlenk, R.F.; Döhner, H.; Campbell, P.J. Genomic classification and prognosis in acute myeloid leukemia. N. Engl. J. Med., 2016, 374(23), 2209-2221.
[http://dx.doi.org/10.1056/NEJMoa1516192] [PMID: 27276561]
[9]
Daver, N.; Schlenk, R.F.; Russell, N.H.; Levis, M.J. Targeting FLT3 mutations in AML: Review of current knowledge and evidence. Leukemia, 2019, 33(2), 299-312.
[http://dx.doi.org/10.1038/s41375-018-0357-9] [PMID: 30651634]
[10]
Zhong, Y.; Qiu, R.Z.; Sun, S.L.; Zhao, C.; Fan, T.Y.; Chen, M.; Li, N.G.; Shi, Z.H. Small-molecule fms-like tyrosine kinase 3 inhibitors: An attractive and efficient method for the treatment of acute myeloid leukemia. J. Med. Chem., 2020, 63(21), 12403-12428.
[http://dx.doi.org/10.1021/acs.jmedchem.0c00696] [PMID: 32659083]
[11]
Hassanein, M.; Almahayni, M.H.; Ahmed, S.O.; Gaballa, S.; El Fakih, R. FLT3 inhibitors for treating acute myeloid leukemia. Clin. Lymphoma Myeloma Leuk., 2016, 16(10), 543-549.
[http://dx.doi.org/10.1016/j.clml.2016.06.002] [PMID: 27450971]
[12]
Tallis, E.; Borthakur, G. Novel treatments for relapsed/refractory acute myeloid leukemia with FLT3 mutations. Expert Rev. Hematol., 2019, 12(8), 621-640.
[http://dx.doi.org/10.1080/17474086.2019.1635882] [PMID: 31232619]
[13]
Wu, M.; Li, C.; Zhu, X. FLT3 inhibitors in acute myeloid leukemia. J. Hematol. Oncol., 2018, 11(1), 133.
[http://dx.doi.org/10.1186/s13045-018-0675-4] [PMID: 30514344]
[14]
Wang, Z.; Cai, J.; Cheng, J.; Yang, W.; Zhu, Y.; Li, H.; Lu, T.; Chen, Y.; Lu, S. FLT3 inhibitors in acute myeloid leukemia: Challenges and recent developments in overcoming resistance. J. Med. Chem., 2021, 64(6), 2878-2900.
[http://dx.doi.org/10.1021/acs.jmedchem.0c01851] [PMID: 33719439]
[15]
Hogan, F.L.; Williams, V.; Knapper, S. FLT3 inhibition in acute myeloid leukaemia – current knowledge and future prospects. Curr. Cancer Drug Targets, 2020, 20(7), 513-531.
[http://dx.doi.org/10.2174/1570163817666200518075820] [PMID: 32418523]
[16]
Zhai, J.; Li, C.; Sun, B.; Wang, S.; Cui, Y.; Gao, Q.; Sang, F. Sunitinib-based Proteolysis Targeting Chimeras (PROTACs) reduced the protein levels of FLT-3 and c-KIT in leukemia cell lines. Bioorg. Med. Chem. Lett., 2022, 78, 129041.
[http://dx.doi.org/10.1016/j.bmcl.2022.129041] [PMID: 36332882]
[17]
O’Farrell, A.M.; Abrams, T.J.; Yuen, H.A.; Ngai, T.J.; Louie, S.G.; Yee, K.W.; Wong, L.M.; Hong, W.; Lee, L.B.; Town, A.; Smolich, B.D.; Manning, W.C.; Murray, L.J.; Heinrich, M.C.; Cherrington, J.M. SU11248 is a novel FLT3 tyrosine kinase inhibitor with potent activity in vitro and in vivo. Blood, 2003, 101(9), 3597-3605.
[PMID: 12531805]
[18]
Chow, L.Q.M.; Eckhardt, S.G. Sunitinib: From rational design to clinical efficacy. J. Clin. Oncol., 2007, 25(7), 884-896.
[http://dx.doi.org/10.1200/JCO.2006.06.3602] [PMID: 17327610]
[19]
Fiedler, W.; Serve, H.; Döhner, H.; Schwittay, M.; Ottmann, O.G.; O’Farrell, A.M.; Bello, C.L.; Allred, R.; Manning, W.C.; Cherrington, J.M.; Louie, S.G.; Hong, W.; Brega, N.M.; Massimini, G.; Scigalla, P.; Berdel, W.E.; Hossfeld, D.K. A phase 1 study of SU11248 in the treatment of patients with refractory or resistant acute myeloid leukemia (AML) or not amenable to conventional therapy for the disease. Blood, 2005, 105(3), 986-993.
[http://dx.doi.org/10.1182/blood-2004-05-1846] [PMID: 15459012]
[20]
Nemes, Z.; Takács-Novák, K.; Völgyi, G.; Valko, K.; Béni, S.; Horváth, Z.; Szokol, B.; Breza, N.; Dobos, J.; Szántai-Kis, C.; Illyés, E.; Boros, S.; Kok, R.J.; Őrfi, L. Synthesis and characterization of amino acid substituted sunitinib analogues for the treatment of AML. Bioorg. Med. Chem. Lett., 2018, 28(14), 2391-2398.
[http://dx.doi.org/10.1016/j.bmcl.2018.06.026] [PMID: 29935772]
[21]
Bensinger, D.; Stubba, D.; Cremer, A.; Kohl, V.; Waßmer, T.; Stuckert, J.; Engemann, V.; Stegmaier, K.; Schmitz, K.; Schmidt, B. Virtual screening identifies irreversible fms-like tyrosine kinase 3 inhibitors with activity toward resistance-conferring mutations. J. Med. Chem., 2019, 62(5), 2428-2446.
[http://dx.doi.org/10.1021/acs.jmedchem.8b01714] [PMID: 30742435]
[22]
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]
[23]
Wang, J.; Pan, X.; Song, Y.; Liu, J.; Ma, F.; Wang, P.; Liu, Y.; Zhao, L.; Kang, D.; Hu, L. Discovery of a potent and selective FLT3 inhibitor ( Z )- N -(5-((5-Fluoro-2-oxoindolin-3-ylidene)methyl)-4-methyl-1 H-pyrrol-3-yl)-3-(pyrrolidin-1-yl)propanamide with improved drug-like properties and superior efficacy in flt3-itd-positive acute myeloid leukemia. J. Med. Chem., 2021, 64(8), 4870-4890.
[http://dx.doi.org/10.1021/acs.jmedchem.0c02247] [PMID: 33797247]
[24]
Marko, D.; Schätzle, S.; Friedel, A.; Genzlinger, A.; Zankl, H.; Meijer, L.; Eisenbrand, G. Inhibition of cyclin-dependent kinase 1 (CDK1) by indirubin derivatives in human tumour cells. Br. J. Cancer, 2001, 84(2), 283-289.
[http://dx.doi.org/10.1054/bjoc.2000.1546] [PMID: 11161389]
[25]
Polychronopoulos, P.; Magiatis, P.; Skaltsounis, A.L.; Myrianthopoulos, V.; Mikros, E.; Tarricone, A.; Musacchio, A.; Roe, S.M.; Pearl, L.; Leost, M.; Greengard, P.; Meijer, L. Structural basis for the synthesis of indirubins as potent and selective inhibitors of glycogen synthase kinase-3 and cyclin-dependent kinases. J. Med. Chem., 2004, 47(4), 935-946.
[http://dx.doi.org/10.1021/jm031016d] [PMID: 14761195]
[26]
Choi, S.J.; Moon, M.J.; Lee, S.D.; Choi, S.U.; Han, S.Y.; Kim, Y.C. Indirubin derivatives as potent FLT3 inhibitors with anti-proliferative activity of acute myeloid leukemic cells. Bioorg. Med. Chem. Lett., 2010, 20(6), 2033-2037.
[http://dx.doi.org/10.1016/j.bmcl.2010.01.039] [PMID: 20153646]
[27]
Han, H.L.J.L.P.J.J.C.S-Y. Discovery of a FLT3 inhibitor LDD1937 as an anti-leukemic agent for acute myeloid leukemia. Oncotarget, 2018, 9(1), 924-936.
[28]
Jeong, P.; Moon, Y.; Lee, J.H.; Lee, S.D.; Park, J.; Lee, J.; Kim, J.; Lee, H.J.; Kim, N.Y.; Choi, J.; Heo, J.D.; Shin, J.E.; Park, H.W.; Kim, Y.G.; Han, S.Y.; Kim, Y.C. Discovery of orally active indirubin-3′-oxime derivatives as potent type 1 FLT3 inhibitors for acute myeloid leukemia. Eur. J. Med. Chem., 2020, 195, 112205.
[http://dx.doi.org/10.1016/j.ejmech.2020.112205] [PMID: 32272419]
[29]
Kleinmaier, R.; Keller, M.; Igel, P.; Buschauer, A.; Gschwind, R.M. Conformations, conformational preferences, and conformational exchange of N′-substituted N-acylguanidines: Intermolecular interactions hold the key. J. Am. Chem. Soc., 2010, 132(32), 11223-11233.
[http://dx.doi.org/10.1021/ja103756y] [PMID: 20698689]
[30]
Solinas, A.; Faure, H.; Roudaut, H.; Traiffort, E.; Schoenfelder, A.; Mann, A.; Manetti, F.; Taddei, M.; Ruat, M. Acylthiourea, acylurea, and acylguanidine derivatives with potent hedgehog inhibiting activity. J. Med. Chem., 2012, 55(4), 1559-1571.
[http://dx.doi.org/10.1021/jm2013369] [PMID: 22268551]
[31]
Jagtap, A.D.; Chang, P.T.; Liu, J.R.; Wang, H.C.; Kondekar, N.B.; Shen, L.J.; Tseng, H.W.; Chen, G.S.; Chern, J.W. Novel acylureidoindolin-2-one derivatives as dual Aurora B/FLT3 inhibitors for the treatment of acute myeloid leukemia. Eur. J. Med. Chem., 2014, 85, 268-288.
[http://dx.doi.org/10.1016/j.ejmech.2014.07.108] [PMID: 25089810]
[32]
El-Hussieny, M.; El-Sayed, N.F.; Fouad, M.A.; Ewies, E.F. Synthesis, biological evaluation and molecular docking of new sulfonamide-based indolinone derivatives as multitargeted kinase inhibitors against leukemia. Bioorg. Chem., 2021, 117, 105421.
[http://dx.doi.org/10.1016/j.bioorg.2021.105421] [PMID: 34666258]
[33]
Shirvani, P.; Fayyazi, N.; Van Belle, S.; Debyser, Z.; Christ, F.; Saghaie, L.; Fassihi, A. Design, synthesis, in silico studies, and antiproliferative evaluations of novel indolin-2-one derivatives containing 3-hydroxy-4-pyridinone fragment. Bioorg. Med. Chem. Lett., 2022, 70, 128784.
[http://dx.doi.org/10.1016/j.bmcl.2022.128784] [PMID: 35569690]
[34]
Zhao, J.C.; Agarwal, S.; Ahmad, H.; Amin, K.; Bewersdorf, J.P.; Zeidan, A.M. A review of FLT3 inhibitors in acute myeloid leukemia. Blood Rev., 2022, 52, 100905.
[http://dx.doi.org/10.1016/j.blre.2021.100905] [PMID: 34774343]
[35]
Gallogly, M.M.; Lazarus, H.M.; Cooper, B.W. Midostaurin: A novel therapeutic agent for patients with FLT3-mutated acute myeloid leukemia and systemic mastocytosis. Ther. Adv. Hematol., 2017, 8(9), 245-261.
[http://dx.doi.org/10.1177/2040620717721459] [PMID: 29051803]
[36]
Levis, M. Midostaurin approved for FLT3-mutated AML. Blood, 2017, 129(26), 3403-3406.
[http://dx.doi.org/10.1182/blood-2017-05-782292] [PMID: 28546144]
[37]
Stone, R.M.; DeAngelo, D.J.; Klimek, V.; Galinsky, I.; Estey, E.; Nimer, S.D.; Grandin, W.; Lebwohl, D.; Wang, Y.; Cohen, P.; Fox, E.A.; Neuberg, D.; Clark, J.; Gilliland, D.G.; Griffin, J.D. Patients with acute myeloid leukemia and an activating mutation in FLT3 respond to a small- molecule FLT3 tyrosine kinase inhibitor, PKC412. Blood, 2005, 105(1), 54-60.
[http://dx.doi.org/10.1182/blood-2004-03-0891] [PMID: 15345597]
[38]
Fischer, T.; Stone, R.M.; DeAngelo, D.J.; Galinsky, I.; Estey, E.; Lanza, C.; Fox, E.; Ehninger, G.; Feldman, E.J.; Schiller, G.J.; Klimek, V.M.; Nimer, S.D.; Gilliland, D.G.; Dutreix, C.; Huntsman-Labed, A.; Virkus, J.; Giles, F.J. Phase IIB trial of oral Midostaurin (PKC412), the FMS- like tyrosine kinase 3 receptor (FLT3) and multi-targeted kinase inhibitor, in patients with acute myeloid leukemia and high-risk myelodysplastic syndrome with either wild- type or mutated FLT3. J. Clin. Oncol., 2010, 28(28), 4339-4345.
[http://dx.doi.org/10.1200/JCO.2010.28.9678] [PMID: 20733134]
[39]
Shabbir, M.; Stuart, R. Lestaurtinib, a multitargeted tyrosinse kinase inhibitor: From bench to bedside. Expert Opin. Investig. Drugs, 2010, 19(3), 427-436.
[http://dx.doi.org/10.1517/13543781003598862] [PMID: 20141349]
[40]
Levis, M.; Allebach, J.; Tse, K-F.; Zheng, R.; Baldwin, B.R.; Smith, B.D.; Jones-Bolin, S.; Ruggeri, B.; Dionne, C.; Small, D. A FLT3-targeted tyrosine kinase inhibitor is cytotoxic to leukemia cells in vitro and in vivo. Blood, 2002, 99(11), 3885-3891.
[http://dx.doi.org/10.1182/blood.V99.11.3885]
[41]
Levis, M.; Ravandi, F.; Wang, E.S.; Baer, M.R.; Perl, A.; Coutre, S.; Erba, H.; Stuart, R.K.; Baccarani, M.; Cripe, L.D.; Tallman, M.S.; Meloni, G.; Godley, L.A.; Langston, A.A.; Amadori, S.; Lewis, I.D.; Nagler, A.; Stone, R.; Yee, K.; Advani, A.; Douer, D.; Wiktor-Jedrzejczak, W.; Juliusson, G.; Litzow, M.R.; Petersdorf, S.; Sanz, M.; Kantarjian, H.M.; Sato, T.; Tremmel, L.; Bensen-Kennedy, D.M.; Small, D.; Smith, B.D. Results from a randomized trial of salvage chemotherapy followed by lestaurtinib for patients with FLT3 mutant AML in first relapse. Blood, 2011, 117(12), 3294-3301.
[http://dx.doi.org/10.1182/blood-2010-08-301796] [PMID: 21270442]
[42]
Gebru, M.T.; Atkinson, J.M.; Young, M.M.; Zhang, L.; Tang, Z.; Liu, Z.; Lu, P.; Dower, C.M.; Chen, L.; Annageldiyev, C.; Sharma, A.; Imamura Kawasawa, Y.; Zhao, Z.; Miller, B.A.; Claxton, D.F.; Wang, H.G. Glucocorticoids enhance the antileukemic activity of FLT3 inhibitors in FLT3-mutant acute myeloid leukemia. Blood, 2020, 136(9), 1067-1079.
[http://dx.doi.org/10.1182/blood.2019003124] [PMID: 32396937]
[43]
Ma, H.; Nguyen, B.; Li, L.; Greenblatt, S.; Williams, A.; Zhao, M.; Levis, M.; Rudek, M.; Duffield, A.; Small, D. TTT-3002 is a novel FLT3 tyrosine kinase inhibitor with activity against FLT3-associated leukemias in vitro and in vivo. Blood, 2014, 123(10), 1525-1534.
[http://dx.doi.org/10.1182/blood-2013-08-523035] [PMID: 24408321]
[44]
Ma, H.S.; Nguyen, B.; Duffield, A.S.; Li, L.; Galanis, A.; Williams, A.B.; Brown, P.A.; Levis, M.J.; Leahy, D.J.; Small, D. FLT3 kinase inhibitor TTT-3002 overcomes both activating and drug resistance mutations in FLT3 in acute myeloid leukemia. Cancer Res., 2014, 74(18), 5206-5217.
[http://dx.doi.org/10.1158/0008-5472.CAN-14-1028] [PMID: 25060518]
[45]
Lopez-Millan, B.; Costales, P.; Gutiérrez-Agüera, F.; Díaz de la Guardia, R.; Roca-Ho, H.; Vinyoles, M.; Rubio-Gayarre, A.; Safi, R.; Castaño, J.; Romecín, P.A.; Ramírez-Orellana, M.; Anguita, E.; Jeremias, I.; Zamora, L.; Rodríguez-Manzaneque, J.C.; Bueno, C.; Morís, F.; Menendez, P. The multi-kinase inhibitor EC-70124 is a promising candidate for the treatment of flt3-itd-positive acute myeloid leukemia. Cancers, 2022, 14(6), 1593.
[http://dx.doi.org/10.3390/cancers14061593] [PMID: 35326743]
[46]
Puente-Moncada, N.; Costales, P.; Antolín, I.; Núñez, L.E.; Oro, P.; Hermosilla, M.A.; Pérez-Escuredo, J.; Ríos-Lombardía, N.; Sanchez-Sanchez, A.M.; Luño, E.; Rodríguez, C.; Martín, V.; Morís, F. Inhibition of FLT3 and PIM kinases by EC-70124 exerts potent activity in preclinical models of acute myeloid leukemia. Mol. Cancer Ther., 2018, 17(3), 614-624.
[http://dx.doi.org/10.1158/1535-7163.MCT-17-0530] [PMID: 29339551]
[47]
Grandage, V.L.; Everington, T.; Linch, D.C.; Khwaja, A. Gö6976 is a potent inhibitor of the JAK 2 and FLT3 tyrosine kinases with significant activity in primary acute myeloid leukaemia cells. Br. J. Haematol., 2006, 135(3), 303-316.
[http://dx.doi.org/10.1111/j.1365-2141.2006.06291.x] [PMID: 16956345]
[48]
Yoshida, A.; Ookura, M.; Zokumasu, K.; Ueda, T. Gö6976, a FLT3 kinase inhibitor, exerts potent cytotoxic activity against acute leukemia via inhibition of survivin and MCL-1. Biochem. Pharmacol., 2014, 90(1), 16-24.
[http://dx.doi.org/10.1016/j.bcp.2014.04.002] [PMID: 24735609]
[49]
Keri, R.S.; Hiremathad, A.; Budagumpi, S.; Nagaraja, B.M. Comprehensive review in current developments of benzimidazole-based medicinal chemistry. Chem. Biol. Drug Des., 2015, 86(1), 19-65.
[http://dx.doi.org/10.1111/cbdd.12462] [PMID: 25352112]
[50]
Vasava, M.S.; Bhoi, M.N.; Rathwa, S.K.; Jethava, D.J.; Acharya, P.T.; Patel, D.B.; Patel, H.D. Benzimidazole: A milestone in the field of medicinal chemistry. Mini Rev. Med. Chem., 2020, 20(7), 532-565.
[http://dx.doi.org/10.2174/1389557519666191122125453] [PMID: 31755386]
[51]
Ali, A.M.; Tawfik, S.S.; Mostafa, A.S.; Massoud, M.A.M. Benzimidazole-based protein kinase inhibitors: Current perspectives in targeted cancer therapy. Chem. Biol. Drug Des., 2022, 100(5), 656-673.
[http://dx.doi.org/10.1111/cbdd.14130] [PMID: 35962624]
[52]
Kampa-Schittenhelm, K.M.; Frey, J.; Haeusser, L.A.; Illing, B.; Pavlovsky, A.A.; Blumenstock, G.; Schittenhelm, M.M. Crenolanib is a type I tyrosine kinase inhibitor that inhibits mutant KIT D816 isoforms prevalent in systemic mastocytosis and core binding factor leukemia. Oncotarget, 2017, 8(47), 82897-82909.
[http://dx.doi.org/10.18632/oncotarget.19970]
[53]
Galanis, A.; Ma, H.; Rajkhowa, T.; Ramachandran, A.; Small, D.; Cortes, J.; Levis, M. Crenolanib is a potent inhibitor of FLT3 with activity against resistance-conferring point mutants. Blood, 2014, 123(1), 94-100.
[http://dx.doi.org/10.1182/blood-2013-10-529313] [PMID: 24227820]
[54]
Zimmerman, E.I.; Turner, D.C.; Buaboonnam, J.; Hu, S.; Orwick, S.; Roberts, M.S.; Janke, L.J.; Ramachandran, A.; Stewart, C.F.; Inaba, H.; Baker, S.D. Crenolanib is active against models of drug-resistant FLT3-ITD−positive acute myeloid leukemia. Blood, 2013, 122(22), 3607-3615.
[http://dx.doi.org/10.1182/blood-2013-07-513044] [PMID: 24046014]
[55]
Friedman, R. The molecular mechanisms behind activation of FLT3 in acute myeloid leukemia and resistance to therapy by selective inhibitors. Biochim. Biophys. Acta Rev. Cancer, 2022, 1877(1), 188666.
[http://dx.doi.org/10.1016/j.bbcan.2021.188666] [PMID: 34896257]
[56]
Garcia, J.S.; Stone, R.M. The development of FLT3 inhibitors in acute myeloid leukemia. Hematol. Oncol. Clin. North Am., 2017, 31(4), 663-680.
[http://dx.doi.org/10.1016/j.hoc.2017.03.002] [PMID: 28673394]
[57]
Kimura, S. AT-9283, a small-molecule multi-targeted kinase inhibitor for the potential treatment of cancer. Curr. Opin. Investig. Drugs, 2010, 11(12), 1442-1449.
[PMID: 21154126]
[58]
Steven Howard, V.B.; John, A. Fragment-based discovery of the pyrazol-4-yl urea (at9283), a multitargeted kinase inhibitor with potent aurora kinase activity. J. Med. Chem., 2009, 52, 379-388.
[59]
Podesta, J.E.; Sugar, R.; Squires, M.; Linardopoulos, S.; Pearson, A.D.J.; Moore, A.S. Adaptation of the plasma inhibitory activity assay to detect Aurora, ABL and FLT3 kinase inhibition by AT9283 in pediatric leukemia. Leuk. Res., 2011, 35(9), 1273-1275.
[http://dx.doi.org/10.1016/j.leukres.2011.05.022] [PMID: 21665275]
[60]
Ravandi, F.; Foran, J.; Verstovsek, S.; Cortes, J.; Wierda, W.; Boone, P.; Borthakur, G.; Sweeney, T.; Kantarjian, H. A phase I trial of AT9283, a multitargeted kinase inhibitor, in patients with refractory hematological malignancies. Blood, 2007, 110(11), 904-904.
[http://dx.doi.org/10.1182/blood.V110.11.904.904]
[61]
Czardybon, W.; Windak, R.; Gołas, A.; Gałęzowski, M.; Sabiniarz, A.; Dolata, I.; Salwińska, M.; Guzik, P.; Zawadzka, M.; Gabor-Worwa, E.; Winnik, B.; Żurawska, M.; Kolasińska, E.; Wincza, E.; Bugaj, M.; Danielewicz, M.; Majewska, E.; Mazan, M.; Dubin, G.; Noyszewska-Kania, M.; Jabłońska, E.; Szydłowski, M.; Sewastianik, T.; Puła, B.; Szumera-Ciećkiewicz, A.; Prochorec-Sobieszek, M.; Mądro, E.; Lech-Marańda, E.; Warzocha, K.; Tamburini, J.; Juszczyński, P.; Brzózka, K. A novel, dual pan-PIM/FLT3 inhibitor SEL24 exhibits broad therapeutic potential in acute myeloid leukemia. Oncotarget, 2018, 9(24), 16917-16931.
[http://dx.doi.org/10.18632/oncotarget.24747] [PMID: 29682194]
[62]
Dokla, E.M.E.; Abdel-Aziz, A.K.; Milik, S.N.; McPhillie, M.J.; Minucci, S.; Abouzid, K.A.M. Discovery of a benzimidazole-based dual FLT3/TrKA inhibitor targeting acute myeloid leukemia. Bioorg. Med. Chem., 2022, 56, 116596.
[http://dx.doi.org/10.1016/j.bmc.2021.116596] [PMID: 35033885]
[63]
Tian, T.; Zhang, S.; Luo, B.; Yin, F.; Lu, W.; Li, Y.; Huang, K.; Liu, Q.; Huang, P.; Garcia-Manero, G.; Wen, S.; Hu, Y. Identification of the benzoimidazole compound as a selective FLT3 inhibitor by cell-based high-throughput screening of a diversity library. J. Med. Chem., 2022, 65(4), 3597-3605.
[http://dx.doi.org/10.1021/acs.jmedchem.1c02079] [PMID: 35148084]
[64]
Yen, S.C.; Chen, L.C.; Huang, H.L.; HuangFu, W.C.; Chen, Y.Y.; Eight Lin, T.; Lien, S.T.; Tseng, H.J.; Sung, T.Y.; Hsieh, J.H.; Huang, W.J.; Pan, S.L.; Hsu, K.C. Identification of a dual FLT3 and MNK2 inhibitor for acute myeloid leukemia treatment using a structure-based virtual screening approach. Bioorg. Chem., 2022, 121, 105675.
[http://dx.doi.org/10.1016/j.bioorg.2022.105675] [PMID: 35182882]
[65]
Goh, K.C.; Novotny-Diermayr, V.; Hart, S.; Ong, L.C.; Loh, Y.K.; Cheong, A.; Tan, Y.C.; Hu, C.; Jayaraman, R.; William, A.D.; Sun, E.T.; Dymock, B.W.; Ong, K.H.; Ethirajulu, K.; Burrows, F.; Wood, J.M. TG02, a novel oral multi-kinase inhibitor of CDKs, JAK2 and FLT3 with potent anti-leukemic properties. Leukemia, 2012, 26(2), 236-243.
[http://dx.doi.org/10.1038/leu.2011.218] [PMID: 21860433]
[66]
Lu, Y.; Ran, T.; Lin, G.; Jin, Q.; Jin, J.; Li, H.; Guo, H.; Lu, T.; Wang, Y. Novel 1H-pyrazole-3-carboxamide derivatives: Synthesis, anticancer evaluation and identification of their DNA-binding interaction. Chem. Pharm. Bull., 2014, 62(3), 238-246.
[http://dx.doi.org/10.1248/cpb.c13-00676] [PMID: 24365978]
[67]
Wang, Y.; Zhi, Y.; Jin, Q.; Lu, S.; Lin, G.; Yuan, H.; Yang, T.; Wang, Z.; Yao, C.; Ling, J.; Guo, H.; Li, T.; Jin, J.; Li, B.; Zhang, L.; Chen, Y.; Lu, T. Discovery of 4-((7 H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)-N-(4-((4-methylpi perazin-1-yl)methyl)phenyl)-1 H-pyrazole-3-carboxamide (FN-1501), an FLT3- and CDK-kinase inhibitor with potentially high efficiency against acute myelocytic leukemia. J. Med. Chem., 2018, 61(4), 1499-1518.
[http://dx.doi.org/10.1021/acs.jmedchem.7b01261] [PMID: 29357250]
[68]
Zhi, Y.; Li, B.; Yao, C.; Li, H.; Chen, P.; Bao, J.; Qin, T.; Wang, Y.; Lu, T.; Lu, S. Discovery of the selective and efficacious inhibitors of FLT3 mutations. Eur. J. Med. Chem., 2018, 155, 303-315.
[http://dx.doi.org/10.1016/j.ejmech.2018.06.010] [PMID: 29894944]
[69]
Zhi, Y.; Wang, Z.; Yao, C.; Li, B.; Heng, H.; Cai, J.; Xiang, L.; Wang, Y.; Lu, T.; Lu, S. Design and synthesis of 4-(heterocyclic Substituted Amino)-1H-Pyrazole-3-carboxamide derivatives and their potent activity against acute myeloid leukemia (AML). Int. J. Mol. Sci., 2019, 20(22), 5739.
[http://dx.doi.org/10.3390/ijms20225739] [PMID: 31731727]
[70]
Lin, W.H.; Hsu, J.T.A.; Hsieh, S.Y.; Chen, C.T.; Song, J.S.; Yen, S.C.; Hsu, T.; Lu, C.T.; Chen, C.H.; Chou, L.H.; Yang, Y.N.; Chiu, C.H.; Chen, C.P.; Tseng, Y.J.; Yen, K.J.; Yeh, C.F.; Chao, Y.S.; Yeh, T.K.; Jiaang, W.T. Discovery of 3-phenyl-1H-5-pyrazolylamine derivatives containing a urea pharmacophore as potent and efficacious inhibitors of FMS-like tyrosine kinase-3 (FLT3). Bioorg. Med. Chem., 2013, 21(11), 2856-2867.
[http://dx.doi.org/10.1016/j.bmc.2013.03.083] [PMID: 23618709]
[71]
Heng, H.; Zhi, Y.; Yuan, H.; Wang, Z.; Li, H.; Wang, S.; Tian, J.; Liu, H.; Chen, Y.; Lu, T.; Ran, T.; Lu, S. Discovery of a highly selective FLT3 inhibitor with specific proliferation inhibition against AML cells harboring FLT3-ITD mutation. Eur. J. Med. Chem., 2019, 163, 195-206.
[http://dx.doi.org/10.1016/j.ejmech.2018.11.063] [PMID: 30508668]
[72]
Heng, H.; Wang, Z.; Li, H.; Huang, Y.; Lan, Q.; Guo, X.; Zhang, L.; Zhi, Y.; Cai, J.; Qin, T.; Xiang, L.; Wang, S.; Chen, Y.; Lu, T.; Lu, S. Combining structure- and property-based optimization to identify selective FLT3-ITD inhibitors with good antitumor efficacy in AML cell inoculated mouse xenograft model. Eur. J. Med. Chem., 2019, 176, 248-267.
[http://dx.doi.org/10.1016/j.ejmech.2019.05.021] [PMID: 31103903]
[73]
Wang, Z.; Cai, J.; Ren, J.; Chen, Y.; Wu, Y.; Cheng, J.; Jia, K.; Huang, F.; Cheng, Z.; Sheng, T.; Song, S.; Heng, H.; Zhu, Y.; Tang, W.; Li, H.; Lu, T.; Chen, Y.; Lu, S. Discovery of a potent FLT3 inhibitor (LT-850-166) with the capacity of overcoming a variety of FLT3 mutations. J. Med. Chem., 2021, 64(19), 14664-14701.
[http://dx.doi.org/10.1021/acs.jmedchem.1c01196] [PMID: 34550682]
[74]
Wilhelm, S.M.; Carter, C.; Tang, L.; Wilkie, D.; McNabola, A.; Rong, H.; Chen, C.; Zhang, X.; Vincent, P.; McHugh, M.; Cao, Y.; Shujath, J.; Gawlak, S.; Eveleigh, D.; Rowley, B.; Liu, L.; Adnane, L.; Lynch, M.; Auclair, D.; Taylor, I.; Gedrich, R.; Voznesensky, A.; Riedl, B.; Post, L.E.; Bollag, G.; Trail, P.A. BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res., 2004, 64(19), 7099-7109.
[http://dx.doi.org/10.1158/0008-5472.CAN-04-1443] [PMID: 15466206]
[75]
Liu, T.; Ivaturi, V.; Sabato, P.; Gobburu, J.V.S.; Greer, J.M.; Wright, J.J.; Smith, B.D.; Pratz, K.W.; Rudek, M.A. Sorafenib dose recommendation in acute myeloid leukemia based on exposure-flt3 relationship. Clin. Transl. Sci., 2018, 11(4), 435-443.
[http://dx.doi.org/10.1111/cts.12555] [PMID: 29702736]
[76]
Zhang, W.; Konopleva, M.; Shi, Y.; McQueen, T.; Harris, D.; Ling, X.; Estrov, Z.; Quintás-Cardama, A.; Small, D.; Cortes, J.; Andreeff, M. Mutant FLT3: A direct target of sorafenib in acute myelogenous leukemia. J. Natl. Cancer Inst., 2008, 100(3), 184-198.
[http://dx.doi.org/10.1093/jnci/djm328] [PMID: 18230792]
[77]
Ravandi, F.; Cortes, J.E.; Jones, D.; Faderl, S.; Garcia- Manero, G.; Konopleva, M.Y.; O’Brien, S.; Estrov, Z.; Borthakur, G.; Thomas, D.; Pierce, S.R.; Brandt, M.; Byrd, A.; Bekele, B.N.; Pratz, K.; Luthra, R.; Levis, M.; Andreeff, M.; Kantarjian, H.M. Phase I/II study of combination therapy with sorafenib, idarubicin, and cytarabine in younger patients with acute myeloid leukemia. J. Clin. Oncol., 2010, 28(11), 1856-1862.
[http://dx.doi.org/10.1200/JCO.2009.25.4888] [PMID: 20212254]
[78]
Morin, S.; Giannotti, F.; Mamez, A.C.; Pradier, A.; Masouridi-Levrat, S.; Simonetta, F.; Chalandon, Y. Real- world experience of sorafenib maintenance after allogeneic hematopoietic stem cell transplantation for FLT3-ITD AML reveals high rates of toxicity-related treatment interruption. Front. Oncol., 2023, 13, 1095870.
[http://dx.doi.org/10.3389/fonc.2023.1095870] [PMID: 37007116]
[79]
Garciaz, S.; Hospital, M.A. FMS-like tyrosine kinase 3 inhibitors in the treatment of acute myeloid leukemia: An update on the emerging evidence and safety profile. OncoTargets Ther., 2023, 16, 31-45.
[http://dx.doi.org/10.2147/OTT.S236740] [PMID: 36698434]
[80]
Yang, L.L.; Li, G.B.; Ma, S.; Zou, C.; Zhou, S.; Sun, Q.Z.; Cheng, C.; Chen, X.; Wang, L.J.; Feng, S.; Li, L.L.; Yang, S.Y. Structure-activity relationship studies of pyrazolo[3,4-d]pyrimidine derivatives leading to the discovery of a novel multikinase inhibitor that potently inhibits FLT3 and VEGFR2 and evaluation of its activity against acute myeloid leukemia in vitro and in vivo. J. Med. Chem., 2013, 56(4), 1641-1655.
[http://dx.doi.org/10.1021/jm301537p] [PMID: 23362959]
[81]
Liang, X.; Wang, B.; Chen, C.; Wang, A.; Hu, C.; Zou, F.; Yu, K.; Liu, Q.; Li, F.; Hu, Z.; Lu, T.; Wang, J.; Wang, L.; Weisberg, E.L.; Li, L.; Xia, R.; Wang, W.; Ren, T.; Ge, J.; Liu, J.; Liu, Q. Discovery of N-(4-(6-acetamidopyrimidin-4-yloxy)phenyl)-2-(2-(trifluoromethyl)phenyl)aceta mide (CHMFL-FLT3-335) as a potent FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) mutant selective inhibitor for acute myeloid leukemia. J. Med. Chem., 2019, 62(2), 875-892.
[http://dx.doi.org/10.1021/acs.jmedchem.8b01594] [PMID: 30565931]
[82]
Cortes, J.E.; Kantarjian, H.; Foran, J.M.; Ghirdaladze, D.; Zodelava, M.; Borthakur, G.; Gammon, G.; Trone, D.; Armstrong, R.C.; James, J.; Levis, M. Phase I study of quizartinib administered daily to patients with relapsed or refractory acute myeloid leukemia irrespective of FMS- like tyrosine kinase 3-internal tandem duplication status. J. Clin. Oncol., 2013, 31(29), 3681-3687.
[http://dx.doi.org/10.1200/JCO.2013.48.8783] [PMID: 24002496]
[83]
Tomoya, A.N.T. quizartinib a selective flt3 inhibitor maintains antileukemic activity in preclinical models of ras-mediated midostaurinresistant acute myeloid leukemia cells. Oncotarget, 2020, 11, 943-955.
[http://dx.doi.org/10.18632/oncotarget.27489]
[84]
Paul, S.; DiPippo, A.J.; Ravandi, F.; Kadia, T.M. Quizartinib in the treatment of FLT3-internal-tandem duplication- positive acute myeloid leukemia. Future Oncol., 2019, 15(34), 3885-3894.
[http://dx.doi.org/10.2217/fon-2019-0353] [PMID: 31559849]
[85]
Chen, C.T.; Hsu, J.T.A.; Lin, W.H.; Lu, C.T.; Yen, S.C.; Hsu, T.; Huang, Y.L.; Song, J.S.; Chen, C.H.; Chou, L.H.; Yen, K.J.; Chen, C.P.; Kuo, P.C.; Huang, C.L.; Liu, H.E.; Chao, Y.S.; Yeh, T.K.; Jiaang, W.T. Identification of a potent 5-phenyl-thiazol-2-ylamine-based inhibitor of FLT3 with activity against drug resistance-conferring point mutations. Eur. J. Med. Chem., 2015, 100, 151-161.
[http://dx.doi.org/10.1016/j.ejmech.2015.05.008] [PMID: 26081023]
[86]
Xu, Y.; Wang, N.Y.; Song, X.J.; Lei, Q.; Ye, T.H.; You, X.Y.; Zuo, W.Q.; Xia, Y.; Zhang, L.D.; Yu, L.T. Discovery of novel N-(5-(tert-butyl)isoxazol-3-yl)-N′-phenylurea analogs as potent FLT3 inhibitors and evaluation of their activity against acute myeloid leukemia in vitro and in vivo. Bioorg. Med. Chem., 2015, 23(15), 4333-4343.
[http://dx.doi.org/10.1016/j.bmc.2015.06.033] [PMID: 26142317]
[87]
Wang, A.; Li, X.; Chen, C.; Wu, H.; Qi, Z.; Hu, C.; Yu, K.; Wu, J.; Liu, J.; Liu, X.; Hu, Z.; Wang, W.; Wang, W.; Wang, W.; Wang, L.; Wang, B.; Liu, Q.; Li, L.; Ge, J.; Ren, T.; Zhang, S.; Xia, R.; Liu, J.; Liu, Q. Discovery of 1-(4-(4-Amino-3-(4-(2-morpholinoethoxy)phenyl)-1 H -pyrazolo[3,4- d ]pyrimidin-1-yl)phenyl)-3-(5-( tert -butyl)isoxazol-3-yl)urea (CHMFL-FLT3-213) as a highly potent type II FLT3 kinase inhibitor capable of overcoming a variety of FLT3 kinase mutants in FLT3-ITD positive AML. J. Med. Chem., 2017, 60(20), 8407-8424.
[http://dx.doi.org/10.1021/acs.jmedchem.7b00840] [PMID: 28956923]
[88]
Yuan, X.; Chen, Y.; Zhang, W.; He, J.; Lei, L.; Tang, M.; Liu, J.; Li, M.; Dou, C.; Yang, T.; Yang, L.; Yang, S.; Wei, Y.; Peng, A.; Niu, T.; Xiang, M.; Ye, H.; Chen, L. Identification of pyrrolo[2,3-d]pyrimidine-based derivatives as potent and orally effective fms-like tyrosine receptor kinase 3 (FLT3) inhibitors for treating acute myelogenous leukemia. J. Med. Chem., 2019, 62(8), 4158-4173.
[http://dx.doi.org/10.1021/acs.jmedchem.9b00223] [PMID: 30939008]
[89]
Cilibrasi, V.; Spanò, V.; Bortolozzi, R.; Barreca, M.; Raimondi, M.V.; Rocca, R.; Maruca, A.; Montalbano, A.; Alcaro, S.; Ronca, R.; Viola, G.; Barraja, P. Synthesis of 2H-Imidazo[2′,1′:2,3] [1,3]thiazolo[4,5-e]isoindol-8-yl-phenylureas with promising therapeutic features for the treatment of acute myeloid leukemia (AML) with FLT3/ITD mutations. Eur. J. Med. Chem., 2022, 235, 114292.
[http://dx.doi.org/10.1016/j.ejmech.2022.114292] [PMID: 35339838]
[90]
Ma, S.; Yang, L.L.; Niu, T.; Cheng, C.; Zhong, L.; Zheng, M.W.; Xiong, Y.; Li, L.L.; Xiang, R.; Chen, L.J.; Zhou, Q.; Wei, Y.Q.; Yang, S.Y. SKLB-677, an FLT3 and Wnt/β-catenin signaling inhibitor, displays potent activity in models of FLT3-driven AML. Sci. Rep., 2015, 5(1), 15646.
[http://dx.doi.org/10.1038/srep15646] [PMID: 26497577]
[91]
Zhang, G.; Zhang, W.; Shen, C.; Nan, J.; Chen, M.; Lai, S.; Zhong, J.; Li, B.; Wang, T.; Wang, Y.; Yang, S.; Li, L. Discovery of small molecule FLT3 inhibitors that are able to overcome drug-resistant mutations. Bioorg. Med. Chem. Lett., 2020, 30(22), 127532.
[http://dx.doi.org/10.1016/j.bmcl.2020.127532] [PMID: 32891702]
[92]
Sellmer, A.; Pilsl, B.; Beyer, M.; Pongratz, H.; Wirth, L.; Elz, S.; Dove, S.; Henninger, S.J.; Spiekermann, K.; Polzer, H.; Klaeger, S.; Kuster, B.; Böhmer, F.D.; Fiebig, H.H.; Krämer, O.H.; Mahboobi, S. A series of novel aryl-methanone derivatives as inhibitors of FMS-like tyrosine kinase 3 (FLT3) in FLT3-ITD-positive acute myeloid leukemia. Eur. J. Med. Chem., 2020, 193, 112232.
[http://dx.doi.org/10.1016/j.ejmech.2020.112232] [PMID: 32199135]
[93]
Zhang, Q.; Zhao, K.; Zhang, L.; Jiao, X.; Zhang, Y.; Tang, C. Synthesis and biological evaluation of diaryl urea derivatives as FLT3 inhibitors. Bioorg. Med. Chem. Lett., 2020, 30(23), 127525.
[http://dx.doi.org/10.1016/j.bmcl.2020.127525] [PMID: 32898697]
[94]
Qi, B.; Xu, X.; Yang, Y.; Zhou, Y.; Chen, T.; Gong, G.; Yue, X.; Xu, X.; Hu, L.; He, H. Discovery of thiazolidin-4-one urea analogues as novel multikinase inhibitors that potently inhibit FLT3 and VEGFR2. Bioorg. Med. Chem., 2019, 27(10), 2127-2139.
[http://dx.doi.org/10.1016/j.bmc.2019.03.049] [PMID: 30940564]
[95]
Xu, X.; Hu, L.; Fan, M.; Hu, Z.; Li, Q.; He, H.; Qi, B. Identification of 1,3-thiazinan-4-one urea-based derivatives as potent FLT3/VEGFR2 dual inhibitors for the treatment of acute myeloid leukemia. J. Mol. Struct., 2022, 1250, 131862.
[http://dx.doi.org/10.1016/j.molstruc.2021.131862]
[96]
Molica, M.; Perrone, S.; Rossi, M. Gilteritinib: The story of a proceeding success into hard-to-treat FLT3-mutated AML patients. J. Clin. Med., 2023, 12(11), 3647.
[http://dx.doi.org/10.3390/jcm12113647] [PMID: 37297842]
[97]
Mori, M.; Kaneko, N.; Ueno, Y.; Yamada, M.; Tanaka, R.; Saito, R.; Shimada, I.; Mori, K.; Kuromitsu, S. Gilteritinib, a FLT3/AXL inhibitor, shows antileukemic activity in mouse models of FLT3 mutated acute myeloid leukemia. Invest. New Drugs, 2017, 35(5), 556-565.
[http://dx.doi.org/10.1007/s10637-017-0470-z] [PMID: 28516360]
[98]
Kang, C.; Blair, H.A. Gilteritinib: A review in relapsed or refractory FLT3-mutated acute myeloid leukaemia. Target. Oncol., 2020, 15(5), 681-689.
[http://dx.doi.org/10.1007/s11523-020-00749-3] [PMID: 32940858]
[99]
Usuki, K.; Sakura, T.; Kobayashi, Y.; Miyamoto, T.; Iida, H.; Morita, S.; Bahceci, E.; Kaneko, M.; Kusano, M.; Yamada, S.; Takeshita, S.; Miyawaki, S.; Naoe, T. Clinical profile of gilteritinib in Japanese patients with relapsed/refractory acute myeloid leukemia: An open-label phase 1 study. Cancer Sci., 2018, 109(10), 3235-3244.
[http://dx.doi.org/10.1111/cas.13749] [PMID: 30039554]
[100]
Jarusiewicz, J.A.; Jeon, J.Y.; Connelly, M.C.; Chen, Y.; Yang, L.; Baker, S.D.; Guy, R.K. Discovery of a diaminopyrimidine FLT3 inhibitor active against acute myeloid leukemia. ACS Omega, 2017, 2(5), 1985-2009.
[http://dx.doi.org/10.1021/acsomega.7b00144] [PMID: 28580438]
[101]
Yamaura, T.; Nakatani, T.; Uda, K.; Ogura, H.; Shin, W.; Kurokawa, N.; Saito, K.; Fujikawa, N.; Date, T.; Takasaki, M.; Terada, D.; Hirai, A.; Akashi, A.; Chen, F.; Adachi, Y.; Ishikawa, Y.; Hayakawa, F.; Hagiwara, S.; Naoe, T.; Kiyoi, H. A novel irreversible FLT3 inhibitor, FF-10101, shows excellent efficacy against AML cells with FLT3 mutations. Blood, 2018, 131(4), 426-438.
[http://dx.doi.org/10.1182/blood-2017-05-786657] [PMID: 29187377]
[102]
Ferng, T.T.; Terada, D.; Ando, M.; Tarver, T.C.; Chaudhary, F.; Lin, K.C.; Logan, A.C.; Smith, C.C. The irreversible FLT3 inhibitor FF-10101 is active against a diversity of FLT3 inhibitor resistance mechanisms. Mol. Cancer Ther., 2022, 21(5), 844-854.
[http://dx.doi.org/10.1158/1535-7163.MCT-21-0317] [PMID: 35395091]
[103]
Hart, S.; Goh, K.C.; Novotny-Diermayr, V.; Tan, Y.C.; Madan, B.; Amalini, C.; Ong, L.C.; Kheng, B.; Cheong, A.; Zhou, J.; Chng, W.J.; Wood, J.M. Pacritinib (SB1518), a JAK2/FLT3 inhibitor for the treatment of acute myeloid leukemia. Blood Cancer J., 2011, 1(11), e44.
[http://dx.doi.org/10.1038/bcj.2011.43] [PMID: 22829080]
[104]
Verstovsek, S.; Odenike, O.; Singer, J.W.; Granston, T.; Al-Fayoumi, S.; Deeg, H.J. Phase 1/2 study of pacritinib, a next generation JAK2/FLT3 inhibitor, in myelofibrosis or other myeloid malignancies. J. Hematol. Oncol., 2016, 9(1), 137.
[http://dx.doi.org/10.1186/s13045-016-0367-x] [PMID: 27931243]
[105]
Yang, T.; Hu, M.; Qi, W.; Yang, Z.; Tang, M.; He, J.; Chen, Y.; Bai, P.; Yuan, X.; Zhang, C.; Liu, K.; Lu, Y.; Xiang, M.; Chen, L. Discovery of potent and orally effective dual janus kinase 2/FLT3 inhibitors for the treatment of acute myelogenous leukemia and myeloproliferative neoplasms. J. Med. Chem., 2019, 62(22), 10305-10320.
[http://dx.doi.org/10.1021/acs.jmedchem.9b01348] [PMID: 31670517]
[106]
Li, X.; Yang, T.; Hu, M.; Yang, Y.; Tang, M.; Deng, D.; Liu, K.; Fu, S.; Tan, Y.; Wang, H.; Chen, Y.; Zhang, C.; Guo, Y.; Peng, B.; Si, W.; Yang, Z.; Chen, L. Synthesis and biological evaluation of 6-(pyrimidin-4-yl)-1H-pyrazolo[4,3-b]pyridine derivatives as novel dual FLT3/CDK4 inhibitors. Bioorg. Chem., 2022, 121, 105669.
[http://dx.doi.org/10.1016/j.bioorg.2022.105669] [PMID: 35180490]
[107]
Long, Y.; Yu, M.; Ochnik, A.M.; Karanjia, J.D.; Basnet, S.K.C.; Kebede, A.A.; Kou, L.; Wang, S. Discovery of novel 4-azaaryl-N-phenylpyrimidin-2-amine derivatives as potent and selective FLT3 inhibitors for acute myeloid leukaemia with FLT3 mutations. Eur. J. Med. Chem., 2021, 213, 113215.
[http://dx.doi.org/10.1016/j.ejmech.2021.113215] [PMID: 33516985]
[108]
Al-Shakliah, N.S.; Attwa, M.W.; AlRabiah, H.; Kadi, A.A. Identification and characterization of in vitro, in vivo, and reactive metabolites of tandutinib using liquid chromatography ion trap mass spectrometry. Anal. Methods, 2021, 13(3), 399-410.
[http://dx.doi.org/10.1039/D0AY02106G] [PMID: 33410830]
[109]
Li, Y.; Ye, T.; Xu, L.; Dong, Y.; Luo, Y.; Wang, C.; Han, Y.; Chen, K.; Qin, M.; Liu, Y.; Zhao, Y. Discovery of 4-piperazinyl-2-aminopyrimidine derivatives as dual inhibitors of JAK2 and FLT3. Eur. J. Med. Chem., 2019, 181, 111590.
[http://dx.doi.org/10.1016/j.ejmech.2019.111590] [PMID: 31408808]
[110]
Tong, L.; Wang, P.; Li, X.; Dong, X.; Hu, X.; Wang, C.; Liu, T.; Li, J.; Zhou, Y. Identification of 2-aminopyrimidine derivatives as FLT3 kinase inhibitors with high selectivity over c-KIT. J. Med. Chem., 2022, 65(4), 3229-3248.
[http://dx.doi.org/10.1021/acs.jmedchem.1c01792] [PMID: 35138851]
[111]
Cho, H.; Shin, I.; Yoon, H.; Jeon, E.; Lee, J.; Kim, Y.; Ryu, S.; Song, C.; Kwon, N.H.; Moon, Y.; Kim, S.; Kim, N.D.; Choi, H.G.; Sim, T. Identification of thieno[3,2-d]pyrimidine derivatives as dual inhibitors of focal adhesion kinase and fms-like tyrosine kinase 3. J. Med. Chem., 2021, 64(16), 11934-11957.
[http://dx.doi.org/10.1021/acs.jmedchem.1c00459] [PMID: 34324343]

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