Small-Molecule CSF1R Inhibitors as Anticancer Agents

Author(s): Qiuju Xun, Zhen Wang, Xianglong Hu, Ke Ding*, Xiaoyun Lu*

Journal Name: Current Medicinal Chemistry

Volume 27 , Issue 23 , 2020

DOI : 10.2174/1573394715666190618121649

  Journal Home
Translate in Chinese
Become EABM
Become Reviewer

Abstract:

Persuasive evidence has been presented linking the infiltration of Tumor-Associated Macrophages (TAMs) with the driving force of tumorigenesis and in the suppression of antitumor immunity. In this context CSF1R, the cellular receptor for Colony Stimulating Factor-1 (CSF1) and Interleukin 34 (IL-34), occupies a central role in manipulating the behavior of TAMs and the dysregulation of CSF1R signaling has been implicated in cancer progression and immunosuppression in many specific cancers. Consequently, CSF1R kinase has been a target of great interest in cancer treatment and significant research efforts have focused on the development of smallmolecule CSF1R inhibitors. In this review, we highlight current progress on the development of these small molecule CSF1R inhibitors as anticancer agents. Special attention is paid to the compounds available in advanced clinical trials.

Keywords: Tumor-Associated Macrophages (TAMs), CSF1R, inhibitors, anticancer agents, pharmacophore features, clinical trials.

[1]
Wynn, T.A.; Chawla, A.; Pollard, J.W. Macrophage biology in development, homeostasis and disease. Nature, 2013, 496(7446), 445-455.
[http://dx.doi.org/10.1038/nature12034] [PMID: 23619691]
[2]
Mantovani, A.; Sozzani, S.; Locati, M.; Allavena, P.; Sica, A. Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol., 2002, 23(11), 549-555.
[http://dx.doi.org/10.1016/S1471-4906(02)02302-5] [PMID: 12401408]
[3]
Noy, R.; Pollard, J.W. Tumor-associated macrophages: from mechanisms to therapy. Immunity, 2014, 41(1), 49-61.
[http://dx.doi.org/10.1016/j.immuni.2014.06.010] [PMID: 25035953]
[4]
Ostuni, R.; Kratochvill, F.; Murray, P.J.; Natoli, G. Macrophages and cancer: from mechanisms to therapeutic implications. Trends Immunol., 2015, 36(4), 229-239.
[http://dx.doi.org/10.1016/j.it.2015.02.004] [PMID: 25770924]
[5]
Pedersen, M.B.; Danielsen, A.V.; Hamilton-Dutoit, S.J.; Bendix, K.; Nørgaard, P.; Møller, M.B.; Steiniche, T.; d’Amore, F. High intratumoral macrophage content is an adverse prognostic feature in anaplastic large cell lymphoma. Histopathology, 2014, 65(4), 490-500.
[http://dx.doi.org/10.1111/his.12407] [PMID: 24592992]
[6]
Ryder, M.; Gild, M.; Hohl, T.M.; Pamer, E.; Knauf, J.; Ghossein, R.; Joyce, J.A.; Fagin, J.A. Genetic and pharmacological targeting of CSF-1/CSF-1R inhibits tumor-associated macrophages and impairs BRAF-induced thyroid cancer progression. PLoS One, 2013, 8(1)e54302
[http://dx.doi.org/10.1371/journal.pone.0054302] [PMID: 23372702]
[7]
Ries, C.H.; Cannarile, M.A.; Hoves, S.; Benz, J.; Wartha, K.; Runza, V.; Rey-Giraud, F.; Pradel, L.P.; Feuerhake, F.; Klaman, I.; Jones, T.; Jucknischke, U.; Scheiblich, S.; Kaluza, K.; Gorr, I.H.; Walz, A.; Abiraj, K.; Cassier, P.A.; Sica, A.; Gomez-Roca, C.; de Visser, K.E.; Italiano, A.; Le Tourneau, C.; Delord, J.P.; Levitsky, H.; Blay, J.Y.; Rüttinger, D. Targeting tumor-associated macrophages with anti-CSF-1R antibody reveals a strategy for cancer therapy. Cancer Cell, 2014, 25(6), 846-859.
[http://dx.doi.org/10.1016/j.ccr.2014.05.016] [PMID: 24898549]
[8]
Jinushi, M.; Komohara, Y. Tumor-associated macrophages as an emerging target against tumors: Creating a new path from bench to bedside. Biochim. Biophys. Acta, 2015, 1855(2), 123-130.
[http://dx.doi.org/10.1016/j.bbcan.2015.01.002] [PMID: 25595840]
[9]
Guo, Q.; Jin, Z.; Yuan, Y.; Liu, R.; Xu, T.; Wei, H.; Xu, X.; He, S.; Chen, S.; Shi, Z.; Hou, W.; Hua, B. New mechanisms of tumor-associated macrophages on promoting tumor progression: recent research advances and potential targets for tumor immunotherapy. J. Immunol. Res., 2016, 2016, 9720912
[http://dx.doi.org/10.1155/2016/9720912] [PMID: 27975071]
[10]
Ngambenjawong, C.; Gustafson, H.H.; Pun, S.H. Progress in tumor-associated macrophage (TAM)-targeted therapeutics. Adv. Drug Deliv. Rev., 2017, 114, 206-221.
[http://dx.doi.org/10.1016/j.addr.2017.04.010] [PMID: 28449873]
[11]
Stanley, E.R.; Berg, K.L.; Einstein, D.B.; Lee, P.S.W.; Pixley, F.J.; Wang, Y.; Yeung, Y.G. Biology and action of colony--stimulating factor-1. Mol. Reprod. Dev., 1997, 46(1), 4-10.
[http://dx.doi.org/10.1002/(SICI)1098-2795(199701)46:1<4:AID-MRD2>3.0.CO;2-V] [PMID: 8981357]
[12]
Yu, W.; Chen, J.; Xiong, Y.; Pixley, F.J.; Yeung, Y.G.; Stanley, E.R. Macrophage proliferation is regulated through CSF-1 receptor tyrosines 544, 559, and 807. J. Biol. Chem., 2012, 287(17), 13694-13704.
[http://dx.doi.org/10.1074/jbc.M112.355610] [PMID: 22375015]
[13]
Hubbard, S.R.; Till, J.H. Protein tyrosine kinase structure and function. Annu. Rev. Biochem., 2000, 69, 373-398.
[http://dx.doi.org/10.1146/annurev.biochem.69.1.373] [PMID: 10966463]
[14]
Lenda, D.M.; Stanley, E.R.; Kelley, V.R. Negative role of colony-stimulating factor-1 in macrophage, T cell, and B cell mediated autoimmune disease in MRL-Fas(lpr) mice. J. Immunol., 2004, 173(7), 4744-4754.
[http://dx.doi.org/10.4049/jimmunol.173.7.4744] [PMID: 15383612]
[15]
Nakano, K.; Okada, Y.; Saito, K.; Tanikawa, R.; Sawamukai, N.; Sasaguri, Y.; Kohro, T.; Wada, Y.; Kodama, T.; Tanaka, Y. Rheumatoid synovial endothelial cells produce macrophage colony-stimulating factor leading to osteoclastogenesis in rheumatoid arthritis. Rheumatology (Oxford), 2007, 46(4), 597-603.
[http://dx.doi.org/10.1093/rheumatology/kel356] [PMID: 17062647]
[16]
Neale, S.D.; Schulze, E.; Smith, R.; Athanasou, N.A. The influence of serum cytokines and growth factors on osteoclast formation in Paget’s disease. QJM, 2002, 95(4), 233-240.
[http://dx.doi.org/10.1093/qjmed/95.4.233] [PMID: 11937650]
[17]
Ohno, H.; Kubo, K.; Murooka, H.; Kobayashi, Y.; Nishitoba, T.; Shibuya, M.; Yoneda, T.; Isoe, T. A c-fms tyrosine kinase inhibitor, Ki20227, suppresses osteoclast differentiation and osteolytic bone destruction in a bone metastasis model. Mol. Cancer Ther., 2006, 5(11), 2634-2643.
[http://dx.doi.org/10.1158/1535-7163.MCT-05-0313] [PMID: 17121910]
[18]
Lenda, D.M.; Kikawada, E.; Stanley, E.R.; Kelley, V.R. Reduced macrophage recruitment, proliferation, and activation in colony-stimulating factor-1-deficient mice results in decreased tubular apoptosis during renal inflammation. J. Immunol., 2003, 170(6), 3254-3262.
[http://dx.doi.org/10.4049/jimmunol.170.6.3254] [PMID: 12626584]
[19]
Shaposhnik, Z.; Wang, X.; Lusis, A.J. Arterial colony stimulating factor-1 influences atherosclerotic lesions by regulating monocyte migration and apoptosis. J. Lipid Res., 2010, 51(7), 1962-1970.
[http://dx.doi.org/10.1194/jlr.M005215] [PMID: 20194110]
[20]
McDermott, R.S.; Deneux, L.; Mosseri, V.; Védrenne, J.; Clough, K.; Fourquet, A.; Rodriguez, J.; Cosset, J.M.; Sastre, X.; Beuzeboc, P.; Pouillart, P.; Scholl, S.M. Circulating macrophage colony stimulating factor as a marker of tumour progression. Eur. Cytokine Netw., 2002, 13(1), 121-127.
[PMID: 11956031]
[21]
Aharinejad, S.; Paulus, P.; Sioud, M.; Hofmann, M.; Zins, K.; Schäfer, R.; Stanley, E.R.; Abraham, D. Colony-stimulating factor-1 blockade by antisense oligonucleotides and small interfering RNAs suppresses growth of human mammary tumor xenografts in mice. Cancer Res., 2004, 64(15), 5378-5384.
[http://dx.doi.org/10.1158/0008-5472.CAN-04-0961] [PMID: 15289345]
[22]
Kubota, Y.; Takubo, K.; Shimizu, T.; Ohno, H.; Kishi, K.; Shibuya, M.; Saya, H.; Suda, T. M-CSF inhibition selectively targets pathological angiogenesis and lymphangiogenesis. J. Exp. M., 2009, 206(5), 1089-1102.
[http://dx.doi.org/10.1084/jem.20081605] [PMID: 19398755]
[23]
Pyonteck, S.M.; Akkari, L.; Schuhmacher, A.J.; Bowman, R.L.; Sevenich, L.; Quail, D.F.; Olson, O.C.; Quick, M.L.; Huse, J.T.; Teijeiro, V.; Setty, M.; Leslie, C.S.; Oei, Y.; Pedraza, A.; Zhang, J.; Brennan, C.W.; Sutton, J.C.; Holland, E.C.; Daniel, D.; Joyce, J.A. CSF-1R inhibition alters macrophage polarization and blocks glioma progression. Nat. Med., 2013, 19(10), 1264-1272.
[http://dx.doi.org/10.1038/nm.3337] [PMID: 24056773]
[24]
Coussens, L.; Van Beveren, C.; Smith, D.; Chen, E.; Mitchell, R.L.; Isacke, C.M.; Verma, I.M.; Ullrich, A. Structural alteration of viral homologue of receptor proto-oncogene fms at carboxyl terminus. Nature, 1986, 320(6059), 277-280.
[http://dx.doi.org/10.1038/320277a0] [PMID: 2421165]
[25]
Kamps, M.P.; Taylor, S.S.; Sefton, B.M. Direct evidence that oncogenic tyrosine kinases and cyclic AMP-dependent protein kinase have homologous ATP-binding sites. Nature, 1984, 310(5978), 589-592.
[http://dx.doi.org/10.1038/310589a0] [PMID: 6431300]
[26]
Sherr, C.J.; Roussel, M.F.; Rettenmier, C.W. Colony-stimulating factor-1 receptor (c-fms). J. Cell. Biochem., 1988, 38(3), 179-187.
[http://dx.doi.org/10.1002/jcb.240380305] [PMID: 2852667]
[27]
Yeung, Y.G.; Stanley, E.R. Proteomic approaches to the analysis of early events in colony-stimulating factor-1 signal transduction. Mol. Cell. Proteomics, 2003, 2(11), 1143-1155.
[http://dx.doi.org/10.1074/mcp.R300009-MCP200] [PMID: 12966146]
[28]
Felix, J.; De Munck, S.; Verstraete, K.; Meuris, L.; Callewaert, N.; Elegheert, J.; Savvides, S.N. Structure and assembly mechanism of the signaling complex mediated by human CSF-1. Structure, 2015, 23(9), 1621-1631.
[http://dx.doi.org/10.1016/j.str.2015.06.019] [PMID: 26235028]
[29]
Chen, X.; Liu, H.; Focia, P.J.; Shim, A.H.; He, X. Structure of macrophage colony stimulating factor bound to FMS: diverse signaling assemblies of class III receptor tyrosine kinases. Proc. Natl. Acad. Sci. USA, 2008, 105(47), 18267-18272.
[http://dx.doi.org/10.1073/pnas.0807762105] [PMID: 19017797]
[30]
Ma, X.; Lin, W.Y.; Chen, Y.; Stawicki, S.; Mukhyala, K.; Wu, Y.; Martin, F.; Bazan, J.F.; Starovasnik, M.A. Structural basis for the dual recognition of helical cytokines IL-34 and CSF-1 by CSF-1R. Structure, 2012, 20(4), 676-687.
[http://dx.doi.org/10.1016/j.str.2012.02.010] [PMID: 22483114]
[31]
Stanley, E.R.; Chitu, V. CSF-1 receptor signaling in myeloid cells. Cold Spring Harb. Perspect. Biol., 2014, 6(6)a021857
[http://dx.doi.org/10.1101/cshperspect.a021857] [PMID: 24890514]
[32]
El-Gamal, M.I.; Anbar, H.S.; Yoo, K.H.; Oh, C.H. FMS kinase inhibitors: current status and future prospects. Med. Res. Rev., 2013, 33(3), 599-636.
[http://dx.doi.org/10.1002/med.21258] [PMID: 22434539]
[33]
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.
[http://dx.doi.org/10.1073/pnas.1219457110] [PMID: 23493555]
[34]
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.
[http://dx.doi.org/10.1016/j.jmb.2007.01.036] [PMID: 17292918]
[35]
Kuropkat, C.; Dünne, A.A.; Plehn, S.; Ossendorf, M.; Herz, U.; Renz, H.; Werner, J.A. Macrophage colony-stimulating factor as a tumor marker for squamous cell carcinoma of the head and neck. Tumour Biol., 2003, 24(5), 236-240.
[http://dx.doi.org/10.1159/000076138] [PMID: 15001836]
[36]
Kang, H.G.; Lee, S.Y.; Jeon, H.S.; Choi, Y.Y.; Kim, S.; Lee, W.K.; Lee, H.C.; Choi, J.E.; Bae, E.Y.; Yoo, S.S.; Lee, J.; Cha, S.I.; Kim, C.H.; Lee, M.H.; Kim, Y.T.; Kim, J.H.; Hong, Y.C.; Kim, Y.H.; Park, J.Y. A functional polymorphism in CSF1R gene is a novel susceptibility marker for lung cancer among never-smoking females. J. Thorac. Oncol., 2014, 9(11), 1647-1655.
[http://dx.doi.org/10.1097/JTO.0000000000000310] [PMID: 25144241]
[37]
Kaminska, J.; Kowalska, M.; Kotowicz, B.; Fuksiewicz, M.; Glogowski, M.; Wojcik, E.; Chechlinska, M.; Steffen, J. Pretreatment serum levels of cytokines and cytokine receptors in patients with non-small cell lung cancer, and correlations with clinicopathological features and prognosis. M-CSF - an independent prognostic factor. Oncology, 2006, 70(2), 115-125.
[http://dx.doi.org/10.1159/000093002] [PMID: 16645324]
[38]
Maher, M.G.; Sapi, E.; Turner, B.; Gumbs, A.; Perrotta, P.L.; Carter, D.; Kacinski, B.M.; Haffty, B.G. Prognostic significance of colony-stimulating factor receptor expression in ipsilateral breast cancer recurrence. Clin. Cancer Res., 1998, 4(8), 1851-1856.
[PMID: 9717811]
[39]
Mroczko, B.; Szmitkowski, M.; Wereszczynska-Siemiatkowska, U.; Jurkowska, G. Stem cell factor and macrophage-colony stimulating factor in patients with pancreatic cancer. Clin. Chem. Lab. Med., 2004, 42(3), 256-260.
[http://dx.doi.org/10.1515/CCLM.2004.047] [PMID: 15080556]
[40]
Richardsen, E.; Uglehus, R.D.; Due, J.; Busch, C.; Busund, L.T.R. The prognostic impact of M-CSF, CSF-1 receptor, CD68 and CD3 in prostatic carcinoma. Histopathology, 2008, 53(1), 30-38.
[http://dx.doi.org/10.1111/j.1365-2559.2008.03058.x] [PMID: 18510570]
[41]
Haran-Ghera, N.; Krautghamer, R.; Lapidot, T.; Peled, A.; Dominguez, M.G.; Stanley, E.R. Increased circulating colony-stimulating factor-1 (CSF-1) in SJL/J mice with radiation-induced acute myeloid leukemia (AML) is associated with autocrine regulation of AML cells by CSF-1. Blood, 1997, 89(7), 2537-2545.
[http://dx.doi.org/10.1182/blood.V89.7.2537] [PMID: 9116300]
[42]
Mroczko, B.; Szmitkowski, M.; Okulczyk, B. Hematopoietic growth factors in colorectal cancer patients. Clin. Chem. Lab. Med., 2003, 41(5), 646-651.
[http://dx.doi.org/10.1515/CCLM.2003.098] [PMID: 12812262]
[43]
Gruessner, C.; Gruessner, A.; Glaser, K.; Abushahin, N.; Laughren, C.; Zheng, W.; Chambers, S.K. Biomarkers and endosalpingiosis in the ovarian and tubal microenvironment of women at high-risk for pelvic serous carcinoma. Am. J. Cancer Res., 2014, 4(1), 61-72.
[PMID: 24482739]
[44]
De, I.; Nikodemova, M.; Steffen, M.D.; Sokn, E.; Maklakova, V.I.; Watters, J.J.; Collier, L.S. CSF1 overexpression has pleiotropic effects on microglia in vivo. Glia, 2014, 62(12), 1955-1967.
[http://dx.doi.org/10.1002/glia.22717] [PMID: 25042473]
[45]
Mok, S.; Tsoi, J.; Koya, R.C.; Hu-Lieskovan, S.; West, B.L.; Bollag, G.; Graeber, T.G.; Ribas, A. Inhibition of colony stimulating factor-1 receptor improves antitumor efficacy of BRAF inhibition. BMC Cancer, 2015, 15, 356.
[http://dx.doi.org/10.1186/s12885-015-1377-8] [PMID: 25939769]
[46]
Espinosa, I.; Edris, B.; Lee, C.H.; Cheng, H.W.; Gilks, C.B.; Wang, Y.; Montgomery, K.D.; Varma, S.; Li, R.; Marinelli, R.J.; West, R.B.; Nielsen, T.; Beck, A.H.; van de Rijn, M. CSF1 expression in nongynecological leiomyosarcoma is associated with increased tumor angiogenesis. Am. J. Pathol., 2011, 179(4), 2100-2107.
[http://dx.doi.org/10.1016/j.ajpath.2011.06.021] [PMID: 21854753]
[47]
De Palma, M.; Murdoch, C.; Venneri, M.A.; Naldini, L.; Lewis, C.E. Tie2-expressing monocytes: regulation of tumor angiogenesis and therapeutic implications. Trends Immunol., 2007, 28(12), 519-524.
[http://dx.doi.org/10.1016/j.it.2007.09.004] [PMID: 17981504]
[48]
De Palma, M.; Venneri, M.A.; Galli, R.; Sergi Sergi, L.; Politi, L.S.; Sampaolesi, M.; Naldini, L. Tie2 identifies a hematopoietic lineage of proangiogenic monocytes required for tumor vessel formation and a mesenchymal population of pericyte progenitors. Cancer Cell, 2005, 8(3), 211-226.
[http://dx.doi.org/10.1016/j.ccr.2005.08.002] [PMID: 16169466]
[49]
Hernandez, L.; Smirnova, T.; Kedrin, D.; Wyckoff, J.; Zhu, L.; Stanley, E.R.; Cox, D.; Muller, W.J.; Pollard, J.W.; Van Rooijen, N.; Segall, J.E. The EGF/CSF-1 paracrine invasion loop can be triggered by heregulin beta1 and CXCL12. Cancer Res., 2009, 69(7), 3221-3227.
[http://dx.doi.org/10.1158/0008-5472.CAN-08-2871] [PMID: 19293185]
[50]
Wyckoff, J.; Wang, W.; Lin, E.Y.; Wang, Y.; Pixley, F.; Stanley, E.R.; Graf, T.; Pollard, J.W.; Segall, J.; Condeelis, J. A paracrine loop between tumor cells and macrophages is required for tumor cell migration in mammary tumors. Cancer Res., 2004, 64(19), 7022-7029.
[http://dx.doi.org/10.1158/0008-5472.CAN-04-1449] [PMID: 15466195]
[51]
Coniglio, S.J.; Eugenin, E.; Dobrenis, K.; Stanley, E.R.; West, B.L.; Symons, M.H.; Segall, J.E. Microglial stimulation of glioblastoma invasion involves epidermal growth factor receptor (EGFR) and colony stimulating factor 1 receptor (CSF-1R) signaling. Mol. Med., 2012, 18, 519-527.
[http://dx.doi.org/10.2119/molmed.2011.00217] [PMID: 22294205]
[52]
Joyce, J.A.; Pollard, J.W. Microenvironmental regulation of metastasis. Nat. Rev. Cancer, 2009, 9(4), 239-252.
[http://dx.doi.org/10.1038/nrc2618] [PMID: 19279573]
[53]
Wyckoff, J.B.; Wang, Y.; Lin, E.Y.; Li, J.F.; Goswami, S.; Stanley, E.R.; Segall, J.E.; Pollard, J.W.; Condeelis, J. Direct visualization of macrophage-assisted tumor cell intravasation in mammary tumors. Cancer Res., 2007, 67(6), 2649-2656.
[http://dx.doi.org/10.1158/0008-5472.CAN-06-1823] [PMID: 17363585]
[54]
Qian, B.; Deng, Y.; Im, J.H.; Muschel, R.J.; Zou, Y.; Li, J.; Lang, R.A.; Pollard, J.W. A distinct macrophage population mediates metastatic breast cancer cell extravasation, establishment and growth. PLoS One, 2009, 4(8)e6562
[http://dx.doi.org/10.1371/journal.pone.0006562] [PMID: 19668347]
[55]
Allavena, P.; Mantovani, A. Immunology in the clinic review series; focus on cancer: tumour-associated macrophages: undisputed stars of the inflammatory tumour microenvironment. Clin. Exp. Immunol., 2012, 167(2), 195-205.
[http://dx.doi.org/10.1111/j.1365-2249.2011.04515.x] [PMID: 22235995]
[56]
Ding, L.; Linsley, P.S.; Huang, L.Y.; Germain, R.N.; Shevach, E.M. IL-10 inhibits macrophage costimulatory activity by selectively inhibiting the up-regulation of B7 expression. J. Immunol., 1993, 151(3), 1224-1234.
[PMID: 7687627]
[57]
Curiel, T.J.; Coukos, G.; Zou, L.; Alvarez, X.; Cheng, P.; Mottram, P.; Evdemon-Hogan, M.; Conejo-Garcia, J.R.; Zhang, L.; Burow, M.; Zhu, Y.; Wei, S.; Kryczek, I.; Daniel, B.; Gordon, A.; Myers, L.; Lackner, A.; Disis, M.L.; Knutson, K.L.; Chen, L.; Zou, W. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat. Med., 2004, 10(9), 942-949.
[http://dx.doi.org/10.1038/nm1093] [PMID: 15322536]
[58]
Butte, M.J.; Keir, M.E.; Phamduy, T.B.; Sharpe, A.H.; Freeman, G.J. Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses. Immunity, 2007, 27(1), 111-122.
[http://dx.doi.org/10.1016/j.immuni.2007.05.016] [PMID: 17629517]
[59]
Daurkin, I.; Eruslanov, E.; Stoffs, T.; Perrin, G.Q.; Algood, C.; Gilbert, S.M.; Rosser, C.J.; Su, L.M.; Vieweg, J.; Kusmartsev, S. Tumor-associated macrophages mediate immunosuppression in the renal cancer microenvironment by activating the 15-lipoxygenase-2 pathway. Cancer Res., 2011, 71(20), 6400-6409.
[http://dx.doi.org/10.1158/0008-5472.CAN-11-1261] [PMID: 21900394]
[60]
Xu, J.; Escamilla, J.; Mok, S.; David, J.; Priceman, S.; West, B.; Bollag, G.; McBride, W.; Wu, L. CSF1R signaling blockade stanches tumor-infiltrating myeloid cells and improves the efficacy of radiotherapy in prostate cancer. Cancer Res., 2013, 73(9), 2782-2794.
[http://dx.doi.org/10.1158/0008-5472.CAN-12-3981] [PMID: 23418320]
[61]
Xuan, Q.J.; Wang, J.X.; Nanding, A.; Wang, Z.P.; Liu, H.; Lian, X.; Zhang, Q.Y. Tumor-associated macrophages are correlated with tamoxifen resistance in the postmenopausal breast cancer patients. Pathol. Oncol. Res., 2014, 20(3), 619-624.
[http://dx.doi.org/10.1007/s12253-013-9740-z] [PMID: 24414992]
[62]
Haegel, H.; Thioudellet, C.; Hallet, R.; Geist, M.; Menguy, T.; Le Pogam, F.; Marchand, J.B.; Toh, M.L.; Duong, V.; Calcei, A.; Settelen, N.; Preville, X.; Hennequi, M.; Grellier, B.; Ancian, P.; Rissanen, J.; Clayette, P.; Guillen, C.; Rooke, R.; Bonnefoy, J.Y. A unique anti-CD115 monoclonal antibody which inhibits osteolysis and skews human monocyte differentiation from M2-polarized macrophages toward dendritic cells. MAbs, 2013, 5(5), 736-747.
[http://dx.doi.org/10.4161/mabs.25743] [PMID: 23924795]
[63]
Grellier, B.; Le Pogam, F.; Vitorino, M.; Starck, J.P.; Geist, M.; Duong, V.; Haegel, H.; Menguy, T.; Bonnefoy, J.Y.; Marchand, J.B.; Ancian, P. 3D modeling and characterization of the human CD115 monoclonal antibody H27K15 epitope and design of a chimeric CD115 target. MAbs, 2014, 6(2), 533-546.
[http://dx.doi.org/10.4161/mabs.27736] [PMID: 24492308]
[64]
Cassier, P.A.; Italiano, A.; Gomez-Roca, C.A.; Le Tourneau, C.; Toulmonde, M.; Cannarile, M.A.; Ries, C.; Brillouet, A.; Müller, C.; Jegg, A.M.; Bröske, A.M.; Dembowski, M.; Bray-French, K.; Freilinger, C.; Meneses-Lorente, G.; Baehner, M.; Harding, R.; Ratnayake, J.; Abiraj, K.; Gass, N.; Noh, K.; Christen, R.D.; Ukarma, L.; Bompas, E.; Delord, J.P.; Blay, J.Y.; Rüttinger, D. CSF1R inhibition with emactuzumab in locally advanced diffuse-type tenosynovial giant cell tumours of the soft tissue: a dose-escalation and dose-expansion phase 1 study. Lancet Oncol., 2015, 16(8), 949-956.
[http://dx.doi.org/10.1016/S1470-2045(15)00132-1] [PMID: 26179200]
[65]
Sankhala, K.K.; Blay, J.Y.; Ganjoo, K.N.; Italiano, A.; Hassan, A.B.; Kim, T.M.; Ravi, V.; Cassier, P.A.; Rutkowski, P.; Sankar, N.; Qazi, I.; Sikorski, R.S.; Collins, H.; Zhang, C.; Shocron, E.; Gelderblom, H. A phase I/II dose escalation and expansion study of cabiralizumab (cabira; FPA-008), an anti-CSF1R antibody, in tenosynovial giant cell tumor (TGCT, diffuse pigmented villonodular synovitis D-PVNS). J. Clin. Oncol., 2017, 35(15)(Suppl.), 11078-11078.
[http://dx.doi.org/10.13140/RG.2.2.18553.16485]
[66]
Haegel, H.; Ziller-Remy, C.; Barraud, L.; Bonnefoy, J.Y.; Cochin, S.; Duong, V.; Geist, M.; Grellier, B.; Hallet, R.; Marchand, J.B.; Menguy, T.; Rooke, R.; Thioudellet, C.; Reymann, C.; Préville, X. Abstract 288: TG3003, an immunomodulatory anti-CD115 mAb targeting M2-macrophage polarization in the tumor microenvironment. Cancer Res., 2015, 75(15)(Suppl.), 288.
[http://dx.doi.org/10.1158/1538-7445.AM2015-288]
[67]
Hulieskovan, S.; Patnaik, A.; Eisenberg, P.; Sachdev, J.; Weise, A.; Kaufman, D.R.; Aromin, I.; West, B.L.; Tong, S.; Ribas, A. Phase 1/2a study of double immune suppression blockade by combining a CSF1R inhibitor (pexidartinib/PLX3397) with an anti PD-1 antibody (pembrolizumab) to treat advanced melanoma and other solid tumors. Gynecol. Oncol., 2016, 141(1), 147-148.
[http://dx.doi.org/10.1016/j.ygyno.2016.04.385]
[68]
Rugo, H.S. Sharma, N.; Reebel, L.; Rodal, M.B.; Peck, A.; West, B.L.; Marimuthu, A.; Karlin, D.A.; Dowlati, A. Le, M.H.; Coussens, L.M.; Wesolowski, R. 447PD - Phase Ib study of Plx3397, a Csf1R inhibitor, and paclitaxel in patients with advanced solid tumors. Ann. Oncol., 2014, 25(Suppl. 4), iv148.
[http://dx.doi.org/10.1093/annonc/mdu331.7]
[69]
Lin, C.C.; Lee, J.H.; Hsu, C.H.; Chen, W.W.; Yen, Y.H.; Yang, C.H.; Zhang, L.; Sasaki, S.I.; Chiu, L.; Cheng, A.L. Abstract A080: a phase 1 study of single-agent pexidartinib in Asian patients with advanced solid tumors (NCT02734433). Mol. Cancer Ther., 2018, 17(1)(Suppl.), A080-A080.
[http://dx.doi.org/10.1158/1535-7163.TARG-17-A080]
[70]
Mérour, J.Y.; Buron, F.; Plé, K.; Bonnet, P.; Routier, S. The azaindole framework in the design of kinase inhibitors. Molecules, 2014, 19(12), 19935-19979.
[http://dx.doi.org/10.3390/molecules191219935] [PMID: 25460315]
[71]
Kang, S.; Bader, A.G.; Vogt, P.K. Phosphatidylinositol 3-kinase mutations identified in human cancer are oncogenic. Proc. Natl. Acad. Sci. USA, 2005, 102(3), 802-807.
[http://dx.doi.org/10.1073/pnas.0408864102] [PMID: 15647370]
[72]
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.
[http://dx.doi.org/10.1056/NEJMoa1411366] [PMID: 26222558]
[73]
Genovese, M.C.; Hsia, E.; Belkowski, S.M.; Chien, C.; Masterson, T.; Thurmond, R.L.; Manthey, C.L.; Yan, X.D.; Ge, T.; Franks, C.; Greenspan, A. Results from a phase IIA parallel group study of JNJ-40346527, an oral CSF-1R inhibitor, in patients with active rheumatoid arthritis despite disease-modifying antirheumatic drug therapy. J. Rheumatol., 2015, 42(10), 1752-1760.
[http://dx.doi.org/10.3899/jrheum.141580] [PMID: 26233509]
[74]
von Tresckow, B.; Morschhauser, F.; Ribrag, V.; Topp, M.S.; Chien, C.; Seetharam, S.; Aquino, R.; Kotoulek, S.; de Boer, C.J.; Engert, A. An open-label, multicenter, phase I/II study of JNJ-40346527, a CSF-1R inhibitor, in patients with relapsed or refractory hodgkin lymphoma. Clin. Cancer Res., 2015, 21(8), 1843-1850.
[http://dx.doi.org/10.1158/1078-0432.CCR-14-1845] [PMID: 25628399]
[75]
Wiesmann, M.; Daniel, D.L.; Pryer, N.; Sutton, J.; Sung, V.; Wang, T.; Jeffry, U.; Oei, Y.; Kaufman, S.; Lenahan, W.; Lee, I.; Huh, K.; Sim, J. Abstract 3629: BLZ945, a selective c-fms (CSF-1R) kinase inhibitor for the suppression of tumor-induced osteolytic lesions in bone. Cancer Res., 2010, 70(8)(Suppl.), 3629-3629.
[76]
Sampson, J.H.; Maus, M.V.; June, C.H. Immunotherapy for Brain Tumors. J. Clin. Oncol., 2017, 35(21), 2450-2456.
[http://dx.doi.org/10.1200/JCO.2017.72.8089] [PMID: 28640704]
[77]
Bendell, J.C.; Tolcher, A.W.; Jones, S.F.; Beeram, M.; Infante, J.R.; Larsen, P.; Rasor, K.; Garrus, J.E.; Li, J.; Cable, P.L.; Eberhardt, C.; Schreiber, J.; Rush, S.; Wood, K.W.; Barrett, E.; Patnaik, A. Abstract A252: a phase 1 study of ARRY-382, an oral inhibitor of colony-stimulating factor-1 receptor (CSF1R), in patients with advanced or metastatic cancers. Mol. Cancer Ther., 2013, 12(11), A252.
[http://dx.doi.org/10.1158/1535-7163.TARG-13-A252]
[78]
Smith, B.D.; Kaufman, M.D.; Leary, C.B.; Hood, M.M.; Lu, W.P.; Turner, B.A.; Vogeti, S.; Wise, S.C.; Flynn, D.L. Abstract A53: the specific FMS kinase inhibitor, DCC-3014, durably inhibits FMS kinase in vivo and blocks cancer bone invasiveness. Cancer Res., 2015, 75(1)(Suppl.), A53-A53.
[http://dx.doi.org/10.1158/1538-7445.CHTME14-A53]
[79]
Smith, B.D.; Leary, C.B.; Lu, W.P.; Kaufman, M.D.; Flynn, D.L. Abstract 4889: the highly specific CSF1R inhibitor DCC-3014 exhibits immunomodulatory and anti-invasive activities in cancer models. Cancer Res., 2016, 76(14)(Suppl.), 4889-4889.
[http://dx.doi.org/10.1158/10.1158/1538-7445.AM2016-4889]
[80]
Cunyat, F.; Rainho, J.N.; West, B.; Swainson, L.; McCune, J.M.; Stevenson, M. Colony-stimulating factor 1 receptor antagonists sensitize human immunodeficiency virus type 1-infected macrophages to TRAIL-mediated killing. J. Virol., 2016, 90(14), 6255-6262.
[http://dx.doi.org/10.1128/JVI.00231-16] [PMID: 27122585]
[81]
Feng, X.; Jopson, T.D.; Paladini, M.S.; Liu, S.; West, B.L.; Gupta, N.; Rosi, S. Colony-stimulating factor 1 receptor blockade prevents fractionated whole-brain irradiation-induced memory deficits. J. Neuroinflammation, 2016, 13(1), 215.
[http://dx.doi.org/10.1186/s12974-016-0671-y] [PMID: 27576527]
[82]
Armstrong, R.C.; Belli, B.; Rowbottom, M.W.; Nepomuceno, R.R.; Dao, A.Q.; Rooks, A.M.; Brigham, D.; McMannus, C.W.; Hocker, M.D.; Holladay, M.W.; Liu, G. Abstract 903: AC708 is a potent and selective inhibitor of CSF1R and reduces tumor associated macrophage infiltration in a breast tumor model. Cancer Res., 2013, 73(8)(Suppl.), 903-903.
[http://dx.doi.org/10.1158/1538-7445.AM2013-903]
[83]
Mok, S.; Duffy, C.; Du, R.; Allison, J.P. Abstract PR01: blocking colony stimulating factor 1 receptor (CSF-1R) and tropomyosin receptor kinase (Trk) improves antitumor efficacy of immunotherapy. Cancer Immunol. Res., 2017, 5(3)(Suppl.), PR01-PR01.
[http://dx.doi.org/10.1158/2326-6074.TUMIMM16-PR01]
[84]
Patch, R.J.; Brandt, B.M.; Asgari, D.; Baindur, N.; Chadha, N.K.; Georgiadis, T.; Cheung, W.S.; Petrounia, I.P.; Donatelli, R.R.; Chaikin, M.A.; Player, M.R. Potent 2′-aminoanilide inhibitors of cFMS as potential anti-inflammatory agents. Bioorg. Med. Chem. Lett., 2007, 17(22), 6070-6074.
[http://dx.doi.org/10.1016/j.bmcl.2007.09.057] [PMID: 17904845]
[85]
Meegalla, S.K.; Wall, M.J.; Chen, J.; Wilson, K.J.; Ballentine, S.K.; Desjarlais, R.L.; Schubert, C.; Crysler, C.S.; Chen, Y.; Molloy, C.J.; Chaikin, M.A.; Manthey, C.L.; Player, M.R.; Tomczuk, B.E.; Illig, C.R. Structure-based optimization of a potent class of arylamide FMS inhibitors. Bioorg. Med. Chem. Lett., 2008, 18(12), 3632-3637.
[http://dx.doi.org/10.1016/j.bmcl.2008.04.059] [PMID: 18495479]
[86]
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.
[http://dx.doi.org/10.1021/jm200900q] [PMID: 22039836]
[87]
Illig, C.R.; Manthey, C.L.; Meegalla, S.K.; Wall, M.J.; Chen, J.; Wilson, K.J.; DesJarlais, R.L.; Ballentine, S.K.; 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. Enhancement of kinase selectivity in a potent class of arylamide FMS inhibitors. Bioorg. Med. Chem. Lett., 2013, 23(23), 6363-6369.
[http://dx.doi.org/10.1016/j.bmcl.2013.09.061] [PMID: 24138939]
[88]
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.
[http://dx.doi.org/10.1016/j.bmcl.2010.01.078] [PMID: 20137931]
[89]
Scott, D.A.; Bell, K.J.; Campbell, C.T.; Cook, D.J.; Dakin, L.A.; Del Valle, D.J.; Drew, L.; Gero, T.W.; Hattersley, M.M.; Omer, C.A.; Tyurin, B.; Zheng, X. 3-amido-4-anilinoquinolines as CSF-1R kinase inhibitors 2: Optimization of the PK profile. Bioorg. Med. Chem. Lett., 2009, 19(3), 701-705.
[http://dx.doi.org/10.1016/j.bmcl.2008.12.044] [PMID: 19114305]
[90]
Drew, L.; Bell, K.; Dakin, L.; Hattersley, M.; Lawson, D.; Repik, G.; Scott, D.; Shen, M.; Omer, C. Abstract #259: the selective CSF-1R inhibitor AZ683 reduces tumor associated macrophages and inhibits growth of breast cancer xenograft models. Cancer Res., 2009, 69(9)(Suppl.), 259-259.
[91]
Scott, D.A.; Dakin, L.A.; Daly, K.; Del Valle, D.J.; Diebold, R.B.; Drew, L.; Ezhuthachan, J.; Gero, T.W.; Ogoe, C.A.; Omer, C.A.; Redmond, S.P.; Repik, G.; Thakur, K.; Ye, Q.; Zheng, X. Mitigation of cardiovascular toxicity in a series of CSF-1R inhibitors, and the identification of AZD7507. Bioorg. Med. Chem. Lett., 2013, 23(16), 4591-4596.
[http://dx.doi.org/10.1016/j.bmcl.2013.06.031] [PMID: 23842474]
[92]
Boulter, L.; Guest, R.V.; Kendall, T.J.; Wilson, D.H.; Wojtacha, D.; Robson, A.J.; Ridgway, R.A.; Samuel, K.; Van Rooijen, N.; Barry, S.T.; Wigmore, S.J.; Sansom, O.J.; Forbes, S.J. WNT signaling drives cholangiocarcinoma growth and can be pharmacologically inhibited. J. Clin. Invest., 2015, 125(3), 1269-1285.
[http://dx.doi.org/10.1172/JCI76452] [PMID: 25689248]
[93]
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.
[http://dx.doi.org/10.1016/j.bmcl.2017.03.064] [PMID: 28377059]
[94]
Im, D.; Jung, K.; Yang, S.; Aman, W.; Hah, J.M. Discovery of 4-arylamido 3-methyl isoxazole derivatives as novel FMS kinase inhibitors. Eur. J. Med. Chem., 2015, 102, 600-610.
[http://dx.doi.org/10.1016/j.ejmech.2015.08.031] [PMID: 26318067]
[95]
Xun, Q.; Zhang, Z.; Luo, J.; Tong, L.; Huang, M.; Wang, Z.; Zou, J.; Liu, Y.; Xu, Y.; Xie, H.; Tu, Z.C.; Lu, X.; Ding, K. Design, synthesis, and structure-activity relationship study of 2-Oxo-3,4-dihydropyrimido[4,5- d]pyrimidines as new colony stimulating factor 1 receptor (csf1r) kinase inhibitors. J. Med. Chem., 2018, 61(6), 2353-2371.
[http://dx.doi.org/10.1021/acs.jmedchem.7b01612] [PMID: 29499108]
[96]
Liao, C.B.; Peng, S.Z.; Ho, C.H.; Lee, C.P.; Chang, J.M.; Huang, H.J.; Ciou, S.Y.; Pan, Y.C.; Chen, Y.K. Abstract 3206: a potent and selective CSF-1R inhibitor, DCR-0064, inhibits colony stimulating factor 1 signaling in vitro and in vivo. Cancer Res., 2017, 77(13)(Suppl.)
[http://dx.doi.org/10.1021/10.1158/1538-7445.AM2017-3206]
[97]
Dewar, A.L.; Cambareri, A.C.; Zannettino, A.C.W.; Miller, B.L.; Doherty, K.V.; Hughes, T.P.; Lyons, A.B. Macrophage colony-stimulating factor receptor c-fms is a novel target of imatinib. Blood, 2005, 105(8), 3127-3132.
[http://dx.doi.org/10.1182/blood-2004-10-3967] [PMID: 15637141]
[98]
Taylor, J.R.; Brownlow, N.; Domin, J.; Dibb, N.J. FMS receptor for M-CSF (CSF-1) is sensitive to the kinase inhibitor imatinib and mutation of Asp-802 to Val confers resistance. Oncogene, 2006, 25(1), 147-151.
[http://dx.doi.org/10.1038/sj.onc.1209007] [PMID: 16170366]
[99]
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.
[http://dx.doi.org/10.1158/1535-7163.MCT-05-0359] [PMID: 16648572]
[100]
Sonpavde, G.; Hutson, T.E.; Rini, B.I. Axitinib for renal cell carcinoma. Expert Opin. Investig. Drugs, 2008, 17(5), 741-748.
[http://dx.doi.org/10.1517/13543784.17.5.741] [PMID: 18447599]
[101]
Murray, L.J.; Abrams, T.J.; Long, K.R.; Ngai, T.J.; Olson, L.M.; Hong, W.; Keast, P.K.; Brassard, J.A.; O’Farrell, A.M.; Cherrington, J.M.; Pryer, N.K. SU11248 inhibits tumor growth and CSF-1R-dependent osteolysis in an experimental breast cancer bone metastasis model. Clin. Exp. Metastasis, 2003, 20(8), 757-766.
[http://dx.doi.org/10.1023/B:CLIN.0000006873.65590.68] [PMID: 14713109]
[102]
Yap, T.A.; Arkenau, H.T.; Camidge, D.R.; George, S.; Serkova, N.J.; Gwyther, S.J.; Spratlin, J.L.; Lal, R.; Spicer, J.; Desouza, N.M.; Leach, M.O.; Chick, J.; Poondru, S.; Boinpally, R.; Gedrich, R.; Brock, K.; Stephens, A.; Eckhardt, S.G.; Kaye, S.B.; Demetri, G.; Scurr, M. First-in-human phase I trial of two schedules of OSI-930, a novel multikinase inhibitor, incorporating translational proof-of-mechanism studies. Clin. Cancer Res., 2013, 19(4), 909-919.
[http://dx.doi.org/10.1158/1078-0432.CCR-12-2258] [PMID: 23403628]
[103]
Poulsen, A.; William, A.; Blanchard, S.; Lee, A.; Nagaraj, H.; Wang, H.; Teo, E.; Tan, E.; Goh, K.C.; Dymock, B. Structure-based design of oxygen-linked macrocyclic kinase inhibitors: discovery of SB1518 and SB1578, potent inhibitors of Janus kinase 2 (JAK2) and Fms-like tyrosine kinase-3 (FLT3). J. Comput. Aided Mol. Des., 2012, 26(4), 437-450.
[http://dx.doi.org/10.1007/s10822-012-9572-z] [PMID: 22527961]
[104]
Fletcher, G.C.; Brokx, R.D.; Denny, T.A.; Hembrough, T.A.; Plum, S.M.; Fogler, W.E.; Sidor, C.F.; Bray, M.R. ENMD-2076 is an orally active kinase inhibitor with antiangiogenic and antiproliferative mechanisms of action. Mol. Cancer Ther., 2011, 10(1), 126-137.
[http://dx.doi.org/10.1158/1535-7163.MCT-10-0574] [PMID: 21177375]
[105]
Zhou, Y.; Shan, S.; Li, Z.B.; Xin, L.J.; Pan, D.S.; Yang, Q.J.; Liu, Y.P.; Yue, X.P.; Liu, X.R.; Gao, J.Z.; Zhang, J.W.; Ning, Z.Q.; Lu, X.P. CS2164, a novel multi-target inhibitor against tumor angiogenesis, mitosis and chronic inflammation with anti-tumor potency. Cancer Sci., 2017, 108(3), 469-477.
[http://dx.doi.org/10.1111/cas.13141] [PMID: 28004478]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 27
ISSUE: 23
Year: 2020
Page: [3944 - 3966]
Pages: 23
DOI: 10.2174/1573394715666190618121649
Price: $65

Article Metrics

PDF: 123
HTML: 3
EPUB: 1
PRC: 2



Most Downloaded Article(s)