Developments of Fms-like Tyrosine Kinase 3 Inhibitors as Anticancer Agents for AML Treatment
- Авторы: Ma C.1, Cui S.2, Xu R.2
-
Учреждения:
- College of Integrated Traditional Chinese and Western Medicine, Shandong University of Traditional Chinese Medicine
- Department of Hematology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine
- Выпуск: Том 31, № 29 (2024)
- Страницы: 4657-4686
- Раздел: Anti-Infectives and Infectious Diseases
- URL: https://rjpbr.com/0929-8673/article/view/645007
- DOI: https://doi.org/10.2174/0109298673277543231205072556
- ID: 645007
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Аннотация
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.
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Об авторах
Chenchen Ma
College of Integrated Traditional Chinese and Western Medicine, Shandong University of Traditional Chinese Medicine
Email: info@benthamscience.net
Siyuan Cui
Department of Hematology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine
Автор, ответственный за переписку.
Email: info@benthamscience.net
Ruirong Xu
Department of Hematology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine
Автор, ответственный за переписку.
Email: info@benthamscience.net
Список литературы
- 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. doi: 10.1016/j.bbrc.2014.02.029 PMID: 24530392
- Short, N.J.; Rytting, M.E.; Cortes, J.E. Acute myeloid leukaemia. Lancet, 2018, 392(10147), 593-606. doi: 10.1016/S0140-6736(18)31041-9 PMID: 30078459
- De Kouchkovsky, I.; Abdul-Hay, M. Acute myeloid leukemia: A comprehensive review and 2016 update. Blood Cancer J., 2016, 6(7), e441. doi: 10.1038/bcj.2016.50 PMID: 27367478
- Rowe, J.M. Changing trends in the therapy of acute myeloid leukemia. Best Pract. Res. Clin. Haematol., 2021, 34(4), 101333. doi: 10.1016/j.beha.2021.101333 PMID: 34865705
- 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. doi: 10.3390/cancers14194897 PMID: 36230820
- Fedorov, K.; Maiti, A.; Konopleva, M. Targeting FLT3 mutation in acute myeloid leukemia: Current strategies and future directions. Cancers, 2023, 15(8), 2312. doi: 10.3390/cancers15082312 PMID: 37190240
- Elgarten, C.W.; Aplenc, R. Pediatric acute myeloid leukemia: Updates on biology, risk stratification, and therapy. Curr. Opin. Pediatr., 2020, 32(1), 57-66. doi: 10.1097/MOP.0000000000000855 PMID: 31815781
- 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.; OMeara, 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. doi: 10.1056/NEJMoa1516192 PMID: 27276561
- 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. doi: 10.1038/s41375-018-0357-9 PMID: 30651634
- 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. doi: 10.1021/acs.jmedchem.0c00696 PMID: 32659083
- 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. doi: 10.1016/j.clml.2016.06.002 PMID: 27450971
- Tallis, E.; Borthakur, G. Novel treatments for relapsed/refractory acute myeloid leukemia with FLT3 mutations. Expert Rev. Hematol., 2019, 12(8), 621-640. doi: 10.1080/17474086.2019.1635882 PMID: 31232619
- Wu, M.; Li, C.; Zhu, X. FLT3 inhibitors in acute myeloid leukemia. J. Hematol. Oncol., 2018, 11(1), 133. doi: 10.1186/s13045-018-0675-4 PMID: 30514344
- 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. doi: 10.1021/acs.jmedchem.0c01851 PMID: 33719439
- 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. doi: 10.2174/1570163817666200518075820 PMID: 32418523
- 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. doi: 10.1016/j.bmcl.2022.129041 PMID: 36332882
- OFarrell, 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
- Chow, L.Q.M.; Eckhardt, S.G. Sunitinib: From rational design to clinical efficacy. J. Clin. Oncol., 2007, 25(7), 884-896. doi: 10.1200/JCO.2006.06.3602 PMID: 17327610
- Fiedler, W.; Serve, H.; Döhner, H.; Schwittay, M.; Ottmann, O.G.; OFarrell, 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. doi: 10.1182/blood-2004-05-1846 PMID: 15459012
- 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. doi: 10.1016/j.bmcl.2018.06.026 PMID: 29935772
- 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. doi: 10.1021/acs.jmedchem.8b01714 PMID: 30742435
- 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. doi: 10.1016/j.ejmech.2016.12.038 PMID: 28038328
- 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. doi: 10.1021/acs.jmedchem.0c02247 PMID: 33797247
- 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. doi: 10.1054/bjoc.2000.1546 PMID: 11161389
- 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. doi: 10.1021/jm031016d PMID: 14761195
- 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. doi: 10.1016/j.bmcl.2010.01.039 PMID: 20153646
- 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.
- 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. doi: 10.1016/j.ejmech.2020.112205 PMID: 32272419
- 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. doi: 10.1021/ja103756y PMID: 20698689
- 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. doi: 10.1021/jm2013369 PMID: 22268551
- 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. doi: 10.1016/j.ejmech.2014.07.108 PMID: 25089810
- 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. doi: 10.1016/j.bioorg.2021.105421 PMID: 34666258
- 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. doi: 10.1016/j.bmcl.2022.128784 PMID: 35569690
- 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. doi: 10.1016/j.blre.2021.100905 PMID: 34774343
- 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. doi: 10.1177/2040620717721459 PMID: 29051803
- Levis, M. Midostaurin approved for FLT3-mutated AML. Blood, 2017, 129(26), 3403-3406. doi: 10.1182/blood-2017-05-782292 PMID: 28546144
- 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. doi: 10.1182/blood-2004-03-0891 PMID: 15345597
- 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. doi: 10.1200/JCO.2010.28.9678 PMID: 20733134
- Shabbir, M.; Stuart, R. Lestaurtinib, a multitargeted tyrosinse kinase inhibitor: From bench to bedside. Expert Opin. Investig. Drugs, 2010, 19(3), 427-436. doi: 10.1517/13543781003598862 PMID: 20141349
- 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. doi: 10.1182/blood.V99.11.3885
- 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. doi: 10.1182/blood-2010-08-301796 PMID: 21270442
- 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. doi: 10.1182/blood.2019003124 PMID: 32396937
- 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. doi: 10.1182/blood-2013-08-523035 PMID: 24408321
- 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. doi: 10.1158/0008-5472.CAN-14-1028 PMID: 25060518
- 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. doi: 10.3390/cancers14061593 PMID: 35326743
- 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. doi: 10.1158/1535-7163.MCT-17-0530 PMID: 29339551
- 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. doi: 10.1111/j.1365-2141.2006.06291.x PMID: 16956345
- 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. doi: 10.1016/j.bcp.2014.04.002 PMID: 24735609
- 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. doi: 10.1111/cbdd.12462 PMID: 25352112
- 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. doi: 10.2174/1389557519666191122125453 PMID: 31755386
- 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. doi: 10.1111/cbdd.14130 PMID: 35962624
- 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. doi: 10.18632/oncotarget.19970
- 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. doi: 10.1182/blood-2013-10-529313 PMID: 24227820
- 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. doi: 10.1182/blood-2013-07-513044 PMID: 24046014
- 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. doi: 10.1016/j.bbcan.2021.188666 PMID: 34896257
- 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. doi: 10.1016/j.hoc.2017.03.002 PMID: 28673394
- 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
- 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.
- 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. doi: 10.1016/j.leukres.2011.05.022 PMID: 21665275
- 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. doi: 10.1182/blood.V110.11.904.904
- 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. doi: 10.18632/oncotarget.24747 PMID: 29682194
- 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. doi: 10.1016/j.bmc.2021.116596 PMID: 35033885
- 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. doi: 10.1021/acs.jmedchem.1c02079 PMID: 35148084
- 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. doi: 10.1016/j.bioorg.2022.105675 PMID: 35182882
- 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. doi: 10.1038/leu.2011.218 PMID: 21860433
- 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. doi: 10.1248/cpb.c13-00676 PMID: 24365978
- 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-pyrrolo2,3-dpyrimidin-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. doi: 10.1021/acs.jmedchem.7b01261 PMID: 29357250
- 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. doi: 10.1016/j.ejmech.2018.06.010 PMID: 29894944
- 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. doi: 10.3390/ijms20225739 PMID: 31731727
- 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. doi: 10.1016/j.bmc.2013.03.083 PMID: 23618709
- 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. doi: 10.1016/j.ejmech.2018.11.063 PMID: 30508668
- 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. doi: 10.1016/j.ejmech.2019.05.021 PMID: 31103903
- 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. doi: 10.1021/acs.jmedchem.1c01196 PMID: 34550682
- 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. doi: 10.1158/0008-5472.CAN-04-1443 PMID: 15466206
- 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. doi: 10.1111/cts.12555 PMID: 29702736
- 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. doi: 10.1093/jnci/djm328 PMID: 18230792
- Ravandi, F.; Cortes, J.E.; Jones, D.; Faderl, S.; Garcia- Manero, G.; Konopleva, M.Y.; OBrien, 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. doi: 10.1200/JCO.2009.25.4888 PMID: 20212254
- 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. doi: 10.3389/fonc.2023.1095870 PMID: 37007116
- 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. doi: 10.2147/OTT.S236740 PMID: 36698434
- 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 pyrazolo3,4-dpyrimidine 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. doi: 10.1021/jm301537p PMID: 23362959
- 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. doi: 10.1021/acs.jmedchem.8b01594 PMID: 30565931
- 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. doi: 10.1200/JCO.2013.48.8783 PMID: 24002496
- 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. doi: 10.18632/oncotarget.27489
- 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. doi: 10.2217/fon-2019-0353 PMID: 31559849
- 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. doi: 10.1016/j.ejmech.2015.05.008 PMID: 26081023
- 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. doi: 10.1016/j.bmc.2015.06.033 PMID: 26142317
- 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 -pyrazolo3,4- 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. doi: 10.1021/acs.jmedchem.7b00840 PMID: 28956923
- 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 pyrrolo2,3-dpyrimidine-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. doi: 10.1021/acs.jmedchem.9b00223 PMID: 30939008
- 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-Imidazo2′,1′:2,3 1,3thiazolo4,5-eisoindol-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. doi: 10.1016/j.ejmech.2022.114292 PMID: 35339838
- 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. doi: 10.1038/srep15646 PMID: 26497577
- 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. doi: 10.1016/j.bmcl.2020.127532 PMID: 32891702
- 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. doi: 10.1016/j.ejmech.2020.112232 PMID: 32199135
- 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. doi: 10.1016/j.bmcl.2020.127525 PMID: 32898697
- 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. doi: 10.1016/j.bmc.2019.03.049 PMID: 30940564
- 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. doi: 10.1016/j.molstruc.2021.131862
- 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. doi: 10.3390/jcm12113647 PMID: 37297842
- 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. doi: 10.1007/s10637-017-0470-z PMID: 28516360
- Kang, C.; Blair, H.A. Gilteritinib: A review in relapsed or refractory FLT3-mutated acute myeloid leukaemia. Target. Oncol., 2020, 15(5), 681-689. doi: 10.1007/s11523-020-00749-3 PMID: 32940858
- 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. doi: 10.1111/cas.13749 PMID: 30039554
- 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. doi: 10.1021/acsomega.7b00144 PMID: 28580438
- 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. doi: 10.1182/blood-2017-05-786657 PMID: 29187377
- 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. doi: 10.1158/1535-7163.MCT-21-0317 PMID: 35395091
- 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. doi: 10.1038/bcj.2011.43 PMID: 22829080
- 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. doi: 10.1186/s13045-016-0367-x PMID: 27931243
- 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. doi: 10.1021/acs.jmedchem.9b01348 PMID: 31670517
- 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-pyrazolo4,3-bpyridine derivatives as novel dual FLT3/CDK4 inhibitors. Bioorg. Chem., 2022, 121, 105669. doi: 10.1016/j.bioorg.2022.105669 PMID: 35180490
- 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. doi: 10.1016/j.ejmech.2021.113215 PMID: 33516985
- 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. doi: 10.1039/D0AY02106G PMID: 33410830
- 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. doi: 10.1016/j.ejmech.2019.111590 PMID: 31408808
- 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. doi: 10.1021/acs.jmedchem.1c01792 PMID: 35138851
- 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 thieno3,2-dpyrimidine derivatives as dual inhibitors of focal adhesion kinase and fms-like tyrosine kinase 3. J. Med. Chem., 2021, 64(16), 11934-11957. doi: 10.1021/acs.jmedchem.1c00459 PMID: 34324343
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