Generic placeholder image

Current Medicinal Chemistry


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

Review Article

Rational Drug Design Approach of Receptor Tyrosine Kinase Type III Inhibitors

Author(s): Cheolhee Kim and Eunae Kim*

Volume 26, Issue 42, 2019

Page: [7623 - 7640] Pages: 18

DOI: 10.2174/0929867325666180622143548

Price: $65


Rational drug design is accomplished through the complementary use of structural biology and computational biology of biological macromolecules involved in disease pathology. Most of the known theoretical approaches for drug design are based on knowledge of the biological targets to which the drug binds. This approach can be used to design drug molecules that restore the balance of the signaling pathway by inhibiting or stimulating biological targets by molecular modeling procedures as well as by molecular dynamics simulations. Type III receptor tyrosine kinase affects most of the fundamental cellular processes including cell cycle, cell migration, cell metabolism, and survival, as well as cell proliferation and differentiation. Many inhibitors of successful rational drug design show that some computational techniques can be combined to achieve synergistic effects.

Keywords: Type III receptor tyrosine kinase, PDGFR, c-KIT, CSF1R, FLT3, rational drug design, computer-aided drug design, molecular modeling, docking simulation, molecular dynamics.

Liao, C.; Sitzmann, M.; Pugliese, A.; Nicklaus, M.C. Software and resources for computational medicinal chemistry. Future Med. Chem., 2011, 3(8), 1057-1085.
[] [PMID: 21707404]
Sliwoski, G.; Kothiwale, S.; Meiler, J.; Lowe, E.W. Jr. Computational methods in drug discovery. Pharmacol. Rev., 2013, 66(1), 334-395.
[] [PMID: 24381236]
Katsila, T.; Spyroulias, G.A.; Patrinos, G.P.; Matsoukas, M.T. Computational approaches in target identification and drug discovery. Comput. Struct. Biotechnol. J., 2016, 14, 177-184.
[] [PMID: 27293534]
Xiang, M.; Cao, Y.; Fan, W.; Chen, L.; Mo, Y. Computer-aided drug design: lead discovery and optimization. Comb. Chem. High Throughput Screen., 2012, 15(4), 328-337.
[] [PMID: 22221065]
Macalino, S.J.; Gosu, V.; Hong, S.; Choi, S. Role of computer-aided drug design in modern drug discovery. Arch. Pharm. Res., 2015, 38(9), 1686-1701.
[] [PMID: 26208641]
Baig, M.H.; Ahmad, K.; Roy, S.; Ashraf, J.M.; Adil, M.; Siddiqui, M.H.; Khan, S.; Kamal, M.A.; Provazník, I.; Choi, I. Computer aided drug design: success and limitations. Curr. Pharm. Des., 2016, 22(5), 572-581.
[] [PMID: 26601966]
Druker, B.J.; Lydon, N.B. Lessons learned from the development of an ABL tyrosine kinase inhibitor for chronic myelogenous leukemia. J. Clin. Invest., 2000, 105(1), 3-7.
[] [PMID: 10619854]
Toledo, L.M.; Lydon, N.B.; Elbaum, D. The structure-based design of ATP-site directed protein kinase inhibitors. Curr. Med. Chem., 1999, 6(9), 775-805.
[PMID: 10495352]
Schindler, T.; Bornmann, W.; Pellicena, P.; Miller, W.T.; Clarkson, B.; Kuriyan, J. Structural mechanism for STI-571 inhibition of abelson tyrosine kinase. Science, 2000, 289(5486), 1938-1942.
[] [PMID: 10988075]
Gorre, M.E.; Mohammed, M.; Ellwood, K.; Hsu, N.; Paquette, R.; Rao, P.N.; Sawyers, C.L. Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science, 2001, 293(5531), 876-880.
[] [PMID: 11423618]
Lee, T-S.; Potts, S.J.; Kantarjian, H.; Cortes, J.; Giles, F.; Albitar, M. Molecular basis explanation for imatinib resistance of BCR-ABL due to T315I and P-loop mutations from molecular dynamics simulations. Cancer, 2008, 112(8), 1744-1753.
[] [PMID: 18338744]
Tokarski, J.S.; Newitt, J.A.; Chang, C.Y.; Cheng, J.D.; Wittekind, M.; Kiefer, S.E.; Kish, K.; Lee, F.Y.; Borzillerri, R.; Lombardo, L.J.; Xie, D.; Zhang, Y.; Klei, H.E. The structure of Dasatinib (BMS-354825) bound to activated ABL kinase domain elucidates its inhibitory activity against imatinib-resistant ABL mutants. Cancer Res., 2006, 66(11), 5790-5797.
[] [PMID: 16740718]
Lierman, E.; Michaux, L.; Beullens, E.; Pierre, P.; Marynen, P.; Cools, J.; Vandenberghe, P. FIP1L1-PDGFRalpha D842V, a novel panresistant mutant, emerging after treatment of FIP1L1-PDGFRalpha T674I eosinophilic leukemia with single agent sorafenib. Leukemia, 2009, 23(5), 845-851.
[] [PMID: 19212337]
O’Hare, T.; Shakespeare, W.C.; Zhu, X.; Eide, C.A.; Rivera, V.M.; Wang, F.; Adrian, L.T.; Zhou, T.; Huang, W.S.; Xu, Q.; Metcalf, C.A., III; Tyner, J.W.; Loriaux, M.M.; Corbin, A.S.; Wardwell, S.; Ning, Y.; Keats, J.A.; Wang, Y.; Sundaramoorthi, R.; Thomas, M.; Zhou, D.; Snodgrass, J.; Commodore, L.; Sawyer, T.K.; Dalgarno, D.C.; Deininger, M.W.; Druker, B.J.; Clackson, T. AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance. Cancer Cell, 2009, 16(5), 401-412.
[] [PMID: 19878872]
Garner, A.P.; Gozgit, J.M.; Anjum, R.; Vodala, S.; Schrock, A.; Zhou, T.; Serrano, C.; Eilers, G.; Zhu, M.; Ketzer, J.; Wardwell, S.; Ning, Y.; Song, Y.; Kohlmann, A.; Wang, F.; Clackson, T.; Heinrich, M.C.; Fletcher, J.A.; Bauer, S.; Rivera, V.M. Ponatinib inhibits polyclonal drug-resistant KIT oncoproteins and shows therapeutic potential in heavily pretreated gastrointestinal stromal tumor (GIST) patients. Clin. Cancer Res., 2014, 20(22), 5745-5755.
[] [PMID: 25239608]
Jin, B.; Ding, K.; Pan, J. Ponatinib induces apoptosis in imatinib-resistant human mast cells by dephosphorylating mutant D816V KIT and silencing β-catenin signaling. Mol. Cancer Ther., 2014, 13(5), 1217-1230.
[] [PMID: 24552773]
Schlessinger, J. Cell signaling by receptor tyrosine kinases. Cell, 2000, 103(2), 211-225.
[] [PMID: 11057895]
Ségaliny, A.I.; Tellez-Gabriel, M.; Heymann, M.F.; Heymann, D. Receptor tyrosine kinases: Characterisation, mechanism of action and therapeutic interests for bone cancers. J. Bone Oncol., 2015, 4(1), 1-12.
[] [PMID: 26579483]
Heldin, C.H.; Lennartsson, J. Structural and functional properties of platelet-derived growth factor and stem cell factor receptors. Cold Spring Harb. Perspect. Biol., 2013, 5(8) a009100
[] [PMID: 23906712]
Liu, H.; Chen, X.; Focia, P.J.; He, X. Structural basis for stem cell factor-KIT signaling and activation of class III receptor tyrosine kinases. EMBO J., 2007, 26(3), 891-901.
[] [PMID: 17255936]
Stanley, E.R.; Chitu, V. CSF-1 receptor signaling in myeloid cells. Cold Spring Harb. Perspect. Biol., 2014, 6(6) a021857
[] [PMID: 24890514]
Grafone, T.; Palmisano, M.; Nicci, C.; Storti, S. An overview on the role of FLT3-tyrosine kinase receptor in acute myeloid leukemia: biology and treatment. Oncol. Rev., 2012, 6(1) e8
[] [PMID: 25992210]
Hunter, T. The role of tyrosine phosphorylation in cell growth and disease. Harvey Lect., 1998-1999, 94, 81-119.
[PMID: 11070953]
Gajiwala, K.S.; Wu, J.C.; Christensen, J.; Deshmukh, G.D.; Diehl, W.; DiNitto, J.P.; English, J.M.; Greig, M.J.; He, Y.A.; Jacques, S.L.; Lunney, E.A.; McTigue, M.; Molina, D.; Quenzer, T.; Wells, P.A.; Yu, X.; Zhang, Y.; Zou, A.; Emmett, M.R.; Marshall, A.G.; Zhang, H.M.; Demetri, G.D. KIT kinase mutants show unique mechanisms of drug resistance to imatinib and sunitinib in gastrointestinal stromal tumor patients. Proc. Natl. Acad. Sci. USA, 2009, 106(5), 1542-1547.
[] [PMID: 19164557]
Wu, P.; Nielsen, T.E.; Clausen, M.H. FDA-approved small-molecule kinase inhibitors. Trends Pharmacol. Sci., 2015, 36(7), 422-439.
[] [PMID: 25975227]
Soroceanu, L.; Akhavan, A.; Cobbs, C.S. Platelet-derived growth factor-alpha receptor activation is required for human cytomegalovirus infection. Nature, 2008, 455(7211), 391-395.
[] [PMID: 18701889]
Lidén, A.; Berg, A.; Nedrebø, T.; Reed, R.K.; Rubin, K. Platelet-derived growth factor BB-mediated normalization of dermal interstitial fluid pressure after mast cell degranulation depends on beta3 but not beta1 integrins. Circ. Res., 2006, 98(5), 635-641.
[] [PMID: 16456102]
Heinrich, M.C.; Corless, C.L.; Duensing, A.; McGreevey, L.; Chen, C.J.; Joseph, N.; Singer, S.; Griffith, D.J.; Haley, A.; Town, A.; Demetri, G.D.; Fletcher, C.D.; Fletcher, J.A. PDGFRA activating mutations in gastrointestinal stromal tumors. Science, 2003, 299(5607), 708-710.
[] [PMID: 12522257]
Andrae, J.; Gallini, R.; Betsholtz, C. Role of platelet-derived growth factors in physiology and medicine. Genes Dev., 2008, 22(10), 1276-1312.
[] [PMID: 18483217]
Liang, L.; Yan, X.E.; Yin, Y.; Yun, C.H. Structural and biochemical studies of the PDGFRA kinase domain. Biochem. Biophys. Res. Commun., 2016, 477(4), 667-672.
[] [PMID: 27349873]
Milletti, F.; Hermann, J.C. Targeted kinase selectivity from kinase profiling data. ACS Med. Chem. Lett., 2012, 3(5), 383-386.
[] [PMID: 24900482]
Grand, F.H.; Burgstaller, S.; Kühr, T.; Baxter, E.J.; Webersinke, G.; Thaler, J.; Chase, A.J.; Cross, N.C. p53-Binding protein 1 is fused to the platelet-derived growth factor receptor beta in a patient with a t(5;15)(q33;q22) and an imatinib-responsive eosinophilic myeloproliferative disorder. Cancer Res., 2004, 64(20), 7216-7219.
[] [PMID: 15492236]
Corless, C.L.; Schroeder, A.; Griffith, D.; Town, A.; McGreevey, L.; Harrell, P.; Shiraga, S.; Bainbridge, T.; Morich, J.; Heinrich, M.C. PDGFRA mutations in gastrointestinal stromal tumors: frequency, spectrum and in vitro sensitivity to imatinib. J. Clin. Oncol., 2005, 23(23), 5357-5364.
[] [PMID: 15928335]
Elling, C.; Erben, P.; Walz, C.; Frickenhaus, M.; Schemionek, M.; Stehling, M.; Serve, H.; Cross, N.C.; Hochhaus, A.; Hofmann, W.K.; Berdel, W.E.; Müller-Tidow, C.; Reiter, A.; Koschmieder, S. Novel imatinib-sensitive PDGFRA-activating point mutations in hypereosinophilic syndrome induce growth factor independence and leukemia-like disease. Blood, 2011, 117(10), 2935-2943.
[] [PMID: 21224473]
von Bubnoff, N.; Gorantla, S.P.; Engh, R.A.; Oliveira, T.M.; Thöne, S.; Aberg, E.; Peschel, C.; Duyster, J. The low frequency of clinical resistance to PDGFR inhibitors in myeloid neoplasms with abnormalities of PDGFRA might be related to the limited repertoire of possible PDGFRA kinase domain mutations in vitro. Oncogene, 2011, 30(8), 933-943.
[] [PMID: 20972453]
Harris, P.A.; Boloor, A.; Cheung, M.; Kumar, R.; Crosby, R.M.; Davis-Ward, R.G.; Epperly, A.H.; Hinkle, K.W.; Hunter, R.N., III; Johnson, J.H.; Knick, V.B.; Laudeman, C.P.; Luttrell, D.K.; Mook, R.A.; Nolte, R.T.; Rudolph, S.K.; Szewczyk, J.R.; Truesdale, A.T.; Veal, J.M.; Wang, L.; Stafford, J.A. Discovery of 5-[[4-[(2,3-dimethyl-2H-indazol-6-yl)methylamino]-2-pyrimidinyl]amino]-2-methyl-benzenesulfonamide (Pazopanib), a novel and potent vascular endothelial growth factor receptor inhibitor. J. Med. Chem., 2008, 51(15), 4632-4640.
[] [PMID: 18620382]
Kumar, R.; Crouthamel, M.C.; Rominger, D.H.; Gontarek, R.R.; Tummino, P.J.; Levin, R.A.; King, A.G. Myelosuppression and kinase selectivity of multikinase angiogenesis inhibitors. Br. J. Cancer, 2009, 101(10), 1717-1723.
[] [PMID: 19844230]
Mahadevan, D.; Cooke, L.; Riley, C.; Swart, R.; Simons, B.; Della Croce, K.; Wisner, L.; Iorio, M.; Shakalya, K.; Garewal, H.; Nagle, R.; Bearss, D. A novel tyrosine kinase switch is a mechanism of imatinib resistance in gastrointestinal stromal tumors. Oncogene, 2007, 26(27), 3909-3919.
[] [PMID: 17325667]
Steeghs, N.; Gelderblom, H.; Roodt, J.O.; Christensen, O.; Rajagopalan, P.; Hovens, M.; Putter, H.; Rabelink, T.J.; de Koning, E. Hypertension and rarefaction during treatment with telatinib, a small molecule angiogenesis inhibitor. Clin. Cancer Res., 2008, 14(11), 3470-3476.
[] [PMID: 18519779]
Lee, K.; Jeong, K.W.; Lee, Y.; Song, J.Y.; Kim, M.S.; Lee, G.S.; Kim, Y. Pharmacophore modeling and virtual screening studies for new VEGFR-2 kinase inhibitors. Eur. J. Med. Chem., 2010, 45(11), 5420-5427.
[] [PMID: 20869793]
Shankar, D.B.; Li, J.; Tapang, P.; Owen McCall, J.; Pease, L.J.; Dai, Y.; Wei, R.Q.; Albert, D.H.; Bouska, J.J.; Osterling, D.J.; Guo, J.; Marcotte, P.A.; Johnson, E.F.; Soni, N.; Hartandi, K.; Michaelides, M.R.; Davidsen, S.K.; Priceman, S.J.; Chang, J.C.; Rhodes, K.; Shah, N.; Moore, T.B.; Sakamoto, K.M.; Glaser, K.B. ABT-869, a multitargeted receptor tyrosine kinase inhibitor: inhibition of FLT3 phosphorylation and signaling in acute myeloid leukemia. Blood, 2007, 109(8), 3400-3408.
[] [PMID: 17209055]
Guo, J.; Marcotte, P.A.; McCall, J.O.; Dai, Y.; Pease, L.J.; Michaelides, M.R.; Davidsen, S.K.; Glaser, K.B. Inhibition of phosphorylation of the colony-stimulating factor-1 receptor (c-Fms) tyrosine kinase in transfected cells by ABT-869 and other tyrosine kinase inhibitors. Mol. Cancer Ther., 2006, 5(4), 1007-1013.
[] [PMID: 16648572]
Ke, Y.Y.; Singh, V.K.; Coumar, M.S.; Hsu, Y.C.; Wang, W.C.; Song, J.S.; Chen, C.H.; Lin, W.H.; Wu, S.H.; Hsu, J.T.; Shih, C.; Hsieh, H.P. Homology modeling of DFG-in FMS-like tyrosine kinase 3 (FLT3) and structure-based virtual screening for inhibitor identification. Sci. Rep., 2015, 5, 11702.
[] [PMID: 26118648]
Ikeda, A.K.; Judelson, D.R.; Federman, N.; Glaser, K.B.; Landaw, E.M.; Denny, C.T.; Sakamoto, K.M. ABT-869 inhibits the proliferation of Ewing Sarcoma cells and suppresses platelet-derived growth factor receptor beta and c-KIT signaling pathways. Mol. Cancer Ther., 2010, 9(3), 653-660.
[] [PMID: 20197394]
Al-Aqtash, R.A.; Zihlif, M.A.; Hammad, H.; Nassar, Z.D.; Meliti, J.A.; Taha, M.O. Ligand-based computational modelling of platelet-derived growth factor beta receptor leading to new angiogenesis inhibitory leads. Comput. Biol. Chem., 2017, 71, 170-179.
[] [PMID: 29101826]
Abbaspour Babaei, M.; Kamalidehghan, B.; Saleem, M.; Huri, H.Z.; Ahmadipour, F. Receptor tyrosine kinase (c-Kit) inhibitors: a potential therapeutic target in cancer cells. Drug Des. Devel. Ther., 2016, 10, 2443-2459.
[] [PMID: 27536065]
Singeltary, B.; Ghose, A.; Sussman, J.; Choe, K.; Olowokure, O. Durable response with a combination of imatinib and sorafenib in KIT exon 17 mutant gastrointestinal stromal tumor. J. Gastrointest. Oncol., 2014, 5(1), E27-E29.
[ 10.3978/j.issn.2078-6891.2013.058] [PMID: 24490049]
Mol, C.D.; Lim, K.B.; Sridhar, V.; Zou, H.; Chien, E.Y.; Sang, B.C.; Nowakowski, J.; Kassel, D.B.; Cronin, C.N.; McRee, D.E. Structure of a c-kit product complex reveals the basis for kinase transactivation. J. Biol. Chem., 2003, 278(34), 31461-31464.
[] [PMID: 12824176]
Mol, C.D.; Dougan, D.R.; Schneider, T.R.; Skene, R.J.; Kraus, M.L.; Scheibe, D.N.; Snell, G.P.; Zou, H.; Sang, B.C.; Wilson, K.P. Structural basis for the autoinhibition and STI-571 inhibition of c-Kit tyrosine kinase. J. Biol. Chem., 2004, 279(30), 31655-31663.
[] [PMID: 15123710]
Zou, J.; Wang, Y.D.; Ma, F.X.; Xiang, M.L.; Shi, B.; Wei, Y.Q.; Yang, S.Y. Detailed conformational dynamics of juxtamembrane region and activation loop in c-Kit kinase activation process. Proteins, 2008, 72(1), 323-332.
[] [PMID: 18214972]
Almerico, A.M.; Tutone, M.; Lauria, A. Receptor-guided 3D-QSAR approach for the discovery of c-kit tyrosine kinase inhibitors. J. Mol. Model., 2012, 18(7), 2885-2895.
[] [PMID: 22127610]
Laine, E.; Auclair, C.; Tchertanov, L. Allosteric communication across the native and mutated KIT receptor tyrosine kinase. PLOS Comput. Biol., 2012, 8(8)e1002661
[] [PMID: 22927810]
Laine, E.; Chauvot de Beauchêne, I.; Perahia, D.; Auclair, C.; Tchertanov, L. Mutation D816V alters the internal structure and dynamics of c-KIT receptor cytoplasmic region: implications for dimerization and activation mechanisms. PLOS Comput. Biol., 2011, 7(6)e1002068
[] [PMID: 21698178]
Chauvot de Beauchêne, I.; Allain, A.; Panel, N.; Laine, E.; Trouvé, A.; Dubreuil, P.; Tchertanov, L. Hotspot mutations in KIT receptor differentially modulate its allosterically coupled conformational dynamics: impact on activation and drug sensitivity. PLOS Comput. Biol., 2014, 10(7)e1003749
[] [PMID: 25079768]
Chow, L.Q.; Eckhardt, S.G. Sunitinib: from rational design to clinical efficacy. J. Clin. Oncol., 2007, 25(7), 884-896.
[] [PMID: 17327610]
Fava, C.; Kantarjian, H.; Cortes, J.; Jabbour, E. Development and targeted use of nilotinib in chronic myeloid leukemia. Drug Des. Devel. Ther., 2009, 2, 233-243.
[ 10.2147/dddt.s3181] [PMID: 19920910]
Huang, W-S.; Zhu, X.; Wang, Y.; Azam, M.; Wen, D.; Sundaramoorthi, R.; Thomas, R.M.; Liu, S.; Banda, G.; Lentini, S.P.; Das, S.; Xu, Q.; Keats, J.; Wang, F.; Wardwell, S.; Ning, Y.; Snodgrass, J.T.; Broudy, M.I.; Russian, K.; Daley, G.Q.; Iuliucci, J.; Dalgarno, D.C.; Clackson, T.; Sawyer, T.K.; Shakespeare, W.C. 9-(Arenethenyl)purines as dual Src/Abl kinase inhibitors targeting the inactive conformation: design, synthesis, and biological evaluation. J. Med. Chem., 2009, 52(15), 4743-4756.
[] [PMID: 19572547]
Gozgit, J.M.; Wong, M.J.; Wardwell, S.; Tyner, J.W.; Loriaux, M.M.; Mohemmad, Q.K.; Narasimhan, N.I.; Shakespeare, W.C.; Wang, F.; Druker, B.J.; Clackson, T.; Rivera, V.M. Potent activity of ponatinib (AP24534) in models of FLT3-driven acute myeloid leukemia and other hematologic malignancies. Mol. Cancer Ther., 2011, 10(6), 1028-1035.
[] [PMID: 21482694]
Jin, Y.; Ding, K.; Li, H.; Xue, M.; Shi, X.; Wang, C.; Pan, J. Ponatinib efficiently kills imatinib-resistant chronic eosinophilic leukemia cells harboring gatekeeper mutant T674I FIP1L1-PDGFRα: roles of Mcl-1 and β-catenin. Mol. Cancer, 2014, 13, 17.
[] [PMID: 24472312]
Wilhelm, S.M.; Dumas, J.; Adnane, L.; Lynch, M.; Carter, C.A.; Schütz, G.; Thierauch, K.H.; Zopf, D. Regorafenib (BAY 73-4506): a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity. Int. J. Cancer, 2011, 129(1), 245-255.
[] [PMID: 21170960]
Zhang, C.; Ibrahim, P.N.; Zhang, J.; Burton, E.A.; Habets, G.; Zhang, Y.; Powell, B.; West, B.L.; Matusow, B.; Tsang, G.; Shellooe, R.; Carias, H.; Nguyen, H.; Marimuthu, A.; Zhang, K.Y.; Oh, A.; Bremer, R.; Hurt, C.R.; Artis, D.R.; Wu, G.; Nespi, M.; Spevak, W.; Lin, P.; Nolop, K.; Hirth, P.; Tesch, G.H.; Bollag, G. Design and pharmacology of a highly specific dual FMS and KIT kinase inhibitor. Proc. Natl. Acad. Sci. USA, 2013, 110(14), 5689-5694.
[] [PMID: 23493555]
Lee, S.; Lee, H.; Kim, J.; Lee, S.; Kim, S.J.; Choi, B.S.; Hong, S.S.; Hong, S. Development and biological evaluation of potent and selective c-KIT(D816V) inhibitors. J. Med. Chem., 2014, 57(15), 6428-6443.
[] [PMID: 25004409]
Park, H.; Lee, S.; Hong, S. Discovery of dual inhibitors for wild type and D816V mutant of c-KIT kinase through virtual and biochemical screening of natural products. J. Nat. Prod., 2016, 79(2), 293-299.
[] [PMID: 26807861]
Walter, M.; Lucet, I.S.; Patel, O.; Broughton, S.E.; Bamert, R.; Williams, N.K.; Fantino, E.; Wilks, A.F.; Rossjohn, J. The 2.7 A crystal structure of the autoinhibited human c-Fms kinase domain. J. Mol. Biol., 2007, 367(3), 839-847.
[] [PMID: 17292918]
Cannarile, M.A.; Weisser, M.; Jacob, W.; Jegg, A.M.; Ries, C.H.; Rüttinger, D. Colony-stimulating factor 1 receptor (CSF1R) inhibitors in cancer therapy. J. Immunother. Cancer, 2017, 5(1), 53.
[] [PMID: 28716061]
Garton, A.J.; Crew, A.P.; Franklin, M.; Cooke, A.R.; Wynne, G.M.; Castaldo, L.; Kahler, J.; Winski, S.L.; Franks, A.; Brown, E.N.; Bittner, M.A.; Keily, J.F.; Briner, P.; Hidden, C.; Srebernak, M.C.; Pirrit, C.; O’Connor, M.; Chan, A.; Vulevic, B.; Henninger, D.; Hart, K.; Sennello, R.; Li, A.H.; Zhang, T.; Richardson, F.; Emerson, D.L.; Castelhano, A.L.; Arnold, L.D.; Gibson, N.W. OSI-930: a novel selective inhibitor of Kit and kinase insert domain receptor tyrosine kinases with antitumor activity in mouse xenograft models. Cancer Res., 2006, 66(2), 1015-1024.
[] [PMID: 16424037]
Schubert, C.; Schalk-Hihi, C.; Struble, G.T.; Ma, H.C.; Petrounia, I.P.; Brandt, B.; Deckman, I.C.; Patch, R.J.; Player, M.R.; Spurlino, J.C.; Springer, B.A. Crystal structure of the tyrosine kinase domain of colony-stimulating factor-1 receptor (cFMS) in complex with two inhibitors. J. Biol. Chem., 2007, 282(6), 4094-4101.
[] [PMID: 17132624]
Huang, H.; Hutta, D.A.; Hu, H.; DesJarlais, R.L.; Schubert, C.; Petrounia, I.P.; Chaikin, M.A.; Manthey, C.L.; Player, M.R. Design and synthesis of a pyrido[2,3-d]pyrimidin-5-one class of anti-inflammatory FMS inhibitors. Bioorg. Med. Chem. Lett., 2008, 18(7), 2355-2361.
[] [PMID: 18342505]
Meyers, M.J.; Pelc, M.; Kamtekar, S.; Day, J.; Poda, G.I.; Hall, M.K.; Michener, M.L.; Reitz, B.A.; Mathis, K.J.; Pierce, B.S.; Parikh, M.D.; Mischke, D.A.; Long, S.A.; Parlow, J.J.; Anderson, D.R.; Thorarensen, A. Structure-based drug design enables conversion of a DFG-in binding CSF-1R kinase inhibitor to a DFG-out binding mode. Bioorg. Med. Chem. Lett., 2010, 20(5), 1543-1547.
[] [PMID: 20137931]
Illig, C.R.; Manthey, C.L.; Wall, M.J.; Meegalla, S.K.; Chen, J.; Wilson, K.J.; Ballentine, S.K.; Desjarlais, R.L.; Schubert, C.; Crysler, C.S.; Chen, Y.; Molloy, C.J.; Chaikin, M.A.; Donatelli, R.R.; Yurkow, E.; Zhou, Z.; Player, M.R.; Tomczuk, B.E. Optimization of a potent class of arylamide colony-stimulating factor-1 receptor inhibitors leading to anti-inflammatory clinical candidate 4-cyano-N-[2-(1-cyclohexen-1-yl)-4-[1-[(dimethylamino)acetyl]-4-piperidinyl]phenyl]-1H-imidazole-2-carboxamide (JNJ-28312141). J. Med. Chem., 2011, 54(22), 7860-7883.
[] [PMID: 22039836]
Machiraju, P.K.; Sarma, J.A.R.P.; Rao, K.R.S.S. gundla1, R. Pharmacophore Modeling and Virtual Screening Studies on Colony Stimulating Factor 1 Receptor (CSF1R) Inhibitors. International Journal of Drug Design and Discovery, 2014, 5(1), 1276-1284.
Huang, H.; Hutta, D.A.; Rinker, J.M.; Hu, H.; Parsons, W.H.; Schubert, C.; DesJarlais, R.L.; Crysler, C.S.; Chaikin, M.A.; Donatelli, R.R.; Chen, Y.; Cheng, D.; Zhou, Z.; Yurkow, E.; Manthey, C.L.; Player, M.R. Pyrido[2,3-d]pyrimidin-5-ones: a novel class of antiinflammatory macrophage colony-stimulating factor-1 receptor inhibitors. J. Med. Chem., 2009, 52(4), 1081-1099.
[] [PMID: 19193011]
Tap, W.D.; Wainberg, Z.A.; Anthony, S.P.; Ibrahim, P.N.; Zhang, C.; Healey, J.H.; Chmielowski, B.; Staddon, A.P.; Cohn, A.L.; Shapiro, G.I.; Keedy, V.L.; Singh, A.S.; Puzanov, I.; Kwak, E.L.; Wagner, A.J.; Von Hoff, D.D.; Weiss, G.J.; Ramanathan, R.K.; Zhang, J.; Habets, G.; Zhang, Y.; Burton, E.A.; Visor, G.; Sanftner, L.; Severson, P.; Nguyen, H.; Kim, M.J.; Marimuthu, A.; Tsang, G.; Shellooe, R.; Gee, C.; West, B.L.; Hirth, P.; Nolop, K.; van de Rijn, M.; Hsu, H.H.; Peterfy, C.; Lin, P.S.; Tong-Starksen, S.; Bollag, G. Structure-guided blockade of CSF1R kinase in tenosynovial giant-cell tumor. N. Engl. J. Med., 2015, 373(5), 428-437.
[] [PMID: 26222558]
Ao, J.Y.; Zhu, X.D.; Chai, Z.T.; Cai, H.; Zhang, Y.Y.; Zhang, K.Z.; Kong, L.Q.; Zhang, N.; Ye, B.G.; Ma, D.N.; Sun, H.C. Colony-stimulating factor 1 receptor blockade inhibits tumor growth by altering the polarization of tumor-associated macrophages in hepatocellular carcinoma. Mol. Cancer Ther., 2017, 16(8), 1544-1554.
[] [PMID: 28572167]
Ramachandran, S.A.; Jadhavar, P.S.; Miglani, S.K.; Singh, M.P.; Kalane, D.P.; Agarwal, A.K.; Sathe, B.D.; Mukherjee, K.; Gupta, A.; Haldar, S.; Raja, M.; Singh, S.; Pham, S.M.; Chakravarty, S.; Quinn, K.; Belmar, S.; Alfaro, I.E.; Higgs, C.; Bernales, S.; Herrera, F.J.; Rai, R. Design, synthesis and optimization of bis-amide derivatives as CSF1R inhibitors. Bioorg. Med. Chem. Lett., 2017, 27(10), 2153-2160.
[] [PMID: 28377059]
Griffith, J.; Black, J.; Faerman, C.; Swenson, L.; Wynn, M.; Lu, F.; Lippke, J.; Saxena, K. The structural basis for autoinhibition of FLT3 by the juxtamembrane domain. Mol. Cell, 2004, 13(2), 169-178.
[] [PMID: 14759363]
Zheng, R.; Bailey, E.; Nguyen, B.; Yang, X.; Piloto, O.; Levis, M.; Small, D. Further activation of FLT3 mutants by FLT3 ligand. Oncogene, 2011, 30(38), 4004-4014.
[] [PMID: 21516120]
Zorn, J.A.; Wang, Q.; Fujimura, E.; Barros, T.; Kuriyan, J. Crystal structure of the FLT3 kinase domain bound to the inhibitor Quizartinib (AC220). PLoS One, 2015, 10(4)e0121177
[] [PMID: 25837374]
Smith, C.C.; Zhang, C.; Lin, K.C.; Lasater, E.A.; Zhang, Y.; Massi, E.; Damon, L.E.; Pendleton, M.; Bashir, A.; Sebra, R.; Perl, A.; Kasarskis, A.; Shellooe, R.; Tsang, G.; Carias, H.; Powell, B.; Burton, E.A.; Matusow, B.; Zhang, J.; Spevak, W.; Ibrahim, P.N.; Le, M.H.; Hsu, H.H.; Habets, G.; West, B.L.; Bollag, G.; Shah, N.P. Characterizing and overriding the structural mechanism of the quizartinib-resistant FLT3 “Gatekeeper” F691L mutation with PLX3397. Cancer Discov., 2015, 5(6), 668-679.
[] [PMID: 25847190]
Smith, C.C.; Lasater, E.A.; Lin, K.C.; Wang, Q.; McCreery, M.Q.; Stewart, W.K.; Damon, L.E.; Perl, A.E.; Jeschke, G.R.; Sugita, M.; Carroll, M.; Kogan, S.C.; Kuriyan, J.; Shah, N.P. Crenolanib is a selective type I pan-FLT3 inhibitor. Proc. Natl. Acad. Sci. USA, 2014, 111(14), 5319-5324.
[] [PMID: 24623852]
Gleixner, K.V.; Peter, B.; Blatt, K.; Suppan, V.; Reiter, A.; Radia, D.; Hadzijusufovic, E.; Valent, P. Synergistic growth-inhibitory effects of ponatinib and midostaurin (PKC412) on neoplastic mast cells carrying KIT D816V. Haematologica, 2013, 98(9), 1450-1457.
[] [PMID: 23539538]
Knapper, S.; Mills, K.I.; Gilkes, A.F.; Austin, S.J.; Walsh, V.; Burnett, A.K. The effects of lestaurtinib (CEP701) and PKC412 on primary AML blasts: the induction of cytotoxicity varies with dependence on FLT3 signaling in both FLT3-mutated and wild-type cases. Blood, 2006, 108(10), 3494-3503.
[] [PMID: 16868253]
Li, X.; Wang, A.; Yu, K.; Qi, Z.; Chen, C.; Wang, W.; Hu, C.; Wu, H.; Wu, J.; Zhao, Z.; Liu, J.; Zou, F.; Wang, L.; Wang, B.; Wang, W.; Zhang, S.; Liu, J.; Liu, Q. Discovery of (R)-1-(3-(4-Amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)-2-(dimethylamino)ethanone (CHMFL-FLT3-122) as a potent and orally available FLT3 kinase inhibitor for FLT3-ITD positive acute myeloid leukemia. J. Med. Chem., 2015, 58(24), 9625-9638.
[] [PMID: 26630553]
Sun, D.; Yang, Y.; Lyu, J.; Zhou, W.; Song, W.; Zhao, Z.; Chen, Z.; Xu, Y.; Li, H. Discovery and Rational Design of Pteridin-7(8H)-one-Based Inhibitors Targeting FMS-like Tyrosine Kinase 3 (FLT3) and Its Mutants. J. Med. Chem., 2016, 59(13), 6187-6200.
[] [PMID: 27266526]
Hatcher, J.M.; Weisberg, E.; Sim, T.; Stone, R.M.; Liu, S.; Griffin, J.D.; Gray, N.S. Discovery of a Highly Potent and Selective Indenoindolone Type 1 Pan-FLT3 Inhibitor. ACS Med. Chem. Lett., 2016, 7(5), 476-481.
[] [PMID: 27190596]
Frett, B.; McConnell, N.; Smith, C.C.; Wang, Y.; Shah, N.P.; Li, H.Y. Computer aided drug discovery of highly ligand efficient, low molecular weight imidazopyridine analogs as FLT3 inhibitors. Eur. J. Med. Chem., 2015, 94, 123-131.
[] [PMID: 25765758]
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)-1H-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.
[] [PMID: 28956923]

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