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Review

Fibroblast growth factor receptor inhibitors: patent review (2015–2019)

, ORCID Icon, & ORCID Icon
Pages 965-977 | Received 12 Sep 2019, Accepted 14 Oct 2019, Published online: 08 Nov 2019

References

  • Eswarakumar VP, Lax I, Schlessinger J. Cellular signaling by fibroblast growth factor receptors. Cytokine Growth Factor Rev. 2005;16:139–149.
  • Sleeman M, Fraser J, Mcdonald M, et al. Identification of a new fibroblast growth factor receptor, FGFR5. Gene. 2001;271:171–182.
  • Ornitz DM, Itoh N. The fibroblast growth factor signaling pathway. Wiley Interdiscip Rev Dev Biol. 2015;4:215–266.
  • Mohammadi M, Olsen SK, Ibrahimi OA. Structural basis for fibroblast growth factor receptor activation. Cytokine Growth Factor Rev. 2005;16:107–137.
  • Kurosu H, Ogawa Y, Miyoshi M, et al. Regulation of fibroblast growth factor-23 signaling by Klotho. J Biol Chem. 2006;281:6120–6123.
  • Richter B, Faul C. FGF23 actions on target tissues—with and without Klotho. Front Endocrinol (Lausanne). 2018;9:1–21.
  • Zhang X, Ibrahimi OA, Olsen SK, et al. receptor specificity of the fibroblast growth factor family THE COMPLETE MAMMALIAN FGF FAMILY. J Biol Chem. 2006;281:15694–15700.
  • Hart KC, Scott C. Robertson and DJD. Identification of tyrosine residues in constitutively activated fibroblast growth factor receptor 3 involved in mitogenesis, stat activation, and phosphatidylinositol 3-kinase activation. Mol Biol Cell. 2001;12:931–942.
  • Lavallee TM, Prudovsky IA, Mcmahon GA, et al. Activation of the MAP kinase pathway by FGF-1 correlates with cell proliferation induction while activation of the src pathway correlates with migration. J Cell Biol. 1998;141:1647–1658.
  • Klint P, Claesson-Welsh L. Signal transduction by fibroblast growth factor receptors. Front Biosci. 1999;4:165–177.
  • Hart KC, Robertson SC, Kanemitsu MY, et al. Transformation and Stat activation by derivatives of FGFR1, FGFR3, and FGFR4. Oncogene. 2000;19:3309–3320.
  • Chae YK, Ranganath K, Hammerman PS, et al. Inhibition of the fibroblast growth factor receptor (FGFR) pathway: the current landscape and barriers to clinical application. Oncotarget. 2017;8:16052–16074.
  • Cihoric N, Savic S, Schneider S, et al. Prognostic role of FGFR1 amplification in early-stage non-small cell lung cancer. Br J Cancer. 2014;110:2914–2922.
  • Sergio Reis-Filho J, Simpson PT, Turner NC, et al. FGFR1 emerges as a potential therapeutictarget for lobular breast Carcinomas. Clin Cancer Res. 2006;12:6652–6662.
  • Pearson A, Smyth E, Babina IS, et al. High-level clonal FGFR amplification and response to FGFR inhibition in a translational clinical trial. Cancer Discov. 2016;6:838–851.
  • Tanizaki J, Ercan D, Capelletti M, et al. Identification of Oncogenic And Drug-Sensitizing Mutations In The Extracellular Domain Of FGFR2. Cancer Res. 2015;75:3139–3146.
  • Dodurga Y, Tataroglu C, Kesen Z, et al. Incidence of fibroblast growth factor receptor 3 gene (FGFR3) A248C, S249C, G372C, and T375C mutations in bladder cancer. Genet Mol Res. 2011;10:86–95.
  • Chesi M, Nardini E, Brents LA, et al. Frequent translocation t(4;14)(p16.3;q32.3) in multiple myeloma is associated with increased expression and activating mutations of fibroblast growth factor receptor 3. Nat Publ Gr. 1997;16:260–264.
  • Takeda M, Arao T, Yokote H, et al. AZD2171 shows potent antitumor activity against gastric cancer over-expressing fibroblast growth factor receptor 2/keratinocyte growth factor receptor. Clin Cancer Res. 2007;13:3051–3057.
  • Dutt A, Salvesen HB, Chen T-H, et al. Drug-sensitive FGFR2 mutations in endometrial carcinoma. Proc Natl Acad Sci. 2008;105:8713–8717.
  • Ishiwata T. Role of fibroblast growth factor receptor-2 splicing in normal and cancer cells. Front Biosci. 2018;23:626–639.
  • Stransky N, Cerami E, Schalm S, et al. The landscape of kinase fusions in cancer. Nat Commun. 2014;5:4846.
  • Wu Y-M, Su F, Kalyana-Sundaram S, et al. Identification of targetable FGFR gene fusions in diverse cancers. Cancer Discov. 2013;3:636–647.
  • Ronca R, Di SE, Giacomini A, et al. Long pentraxin-3 inhibits epithelial-mesenchymal transition in melanoma cells. Mol Cancer Res. 2013;12:2760–2771.
  • Marek L, Ware KE, Fritzsche A, et al. Fibroblast Growth Factor (FGF) and FGF receptor-mediated autocrine signaling in non-small-cell lung cancer cells. Mol Pharmacol. 2009;75:196–207.
  • Aukes K, Forsman C, Brady NJ, et al. Breast cancer cell-derived fibroblast growth factors enhance osteoclast activity and contribute to the formation of metastatic lesions. PloS One. 2017;12:e0185736.
  • Nguyen M, Watanabe H, Budson AE, et al. Elevated levels of an angiogenic peptide, basic fibroblast growth factor, in the urine of patients with a wide spectrum of cancers. J Natl Cancer Inst. 1994;86:356–361.
  • Ruotsalainen T, Joensuu H, Mattson K, et al. High pretreatment serum concentration of basic fibroblast growth factor is a predictor of poor prognosis in small cell lung cancer. Cancer Epidemiol Biomarkers Prev. 2002;11:1492–1495.
  • Desnoyers LR, Pai R, Ferrando RE, et al. Targeting FGF19 inhibits tumor growth in colon cancer xenograft and FGF19 transgenic hepatocellular carcinoma models. Oncogene. 2008;27:85–97.
  • Wu X, Ge H, Lemon B, et al. FGF19-induced hepatocyte proliferation is mediated through FGFR4 activation. J Biol Chem. 2010;285:5165–5170.
  • Ronca R, Giacomini A, Rusnati M, et al. The potential of fibroblast growth factor/fibroblast growth factor receptor signaling as a therapeutic target in tumor angiogenesis. Expert Opin Ther Targets. 2015;19:1361–1377.
  • Presta M, Dell’Era P, Mitola S, et al. Fibroblast growth factor/fibroblast growth factor receptor system in angiogenesis. Cytokine Growth Factor Rev. 2005;16:159–178.
  • Lieu C, Heymach J, Overman M, et al. Beyond VEGF: inhibition of the Fibroblast Growth Factor Pathway and Antiangiogenesis. Clin Cancer Res. 2011;17:6130–6139.
  • Zhang J, Yang PL, Gray NS. Targeting cancer with small molecule kinase inhibitors. Nat Rev Cancer. 2009;9:28–39.
  • Renhowe PA, Pecchi S, Shafer CM, et al. Design, structure-activity relationships and in vivo characterization of 4-Amino-3-benzimidazol-2-ylhydroquinolin-2-ones: novel class of receptor tyrosine kinase inhibitors. J Med Chem. 2009;52:278–292.
  • Roth GJ, Binder R, Colbatzky F, et al. Nintedanib: from discovery to the clinic. J Med Chem. 2015;58:1053–1063.
  • Matsui J, Funahashi Y, Uenaka T, et al. Multi-kinase inhibitor E7080 suppresses lymph node and lung metastases of human mammary breast tumor MDA-MB-231 via inhibition of vascular endothelial growth factor-receptor (VEGF-R) 2 and VEGF-R3 kinase. Clin Cancer Res. 2008;14:5459–5465.
  • Huang WS, Metcalf CA, Sundaramoorthi R, et al. Discovery of 3-[2-(imidazo[1,2- b]pyridazin-3-yl)ethynyl]-4-methyl- N -{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide (AP24534), a potent, orally active pan-inhibitor of breakpoint cluster region-abelson (BCR-ABL) kinase. J Med Chem. 2010;53:4701–4719.
  • Hall TG, Yu Y, Eathiraj S, et al. Preclinical activity of ARQ 087, a novel inhibitor targeting FGFR dysregulation. PLoS One. 2016;11:3–5.
  • Watanabe Miyano S, Yamamoto Y, Kodama K, et al. E7090, a novel selective inhibitor of fibroblast growth factor receptors, displays potent antitumor activity and prolongs survival in preclinical models. Mol Cancer Ther. 2016;15:2630–2639.
  • Babina IS, Turner NC. Advances and challenges in targeting FGFR signalling in cancer. Nat Publ Gr. 2017;17:318–332.
  • Hierro C, Rodon J, Tabernero J. Fibroblast Growth Factor (FGF) Receptor/FGF inhibitors: novel targets and strategies for optimization of response of solid tumors. Semin Oncol. 2015;42:801–819.
  • Katoh M. FGFR inhibitors: effects on cancer cells, tumor microenvironment and whole-body homeostasis (Review). Int J Mol Med. 2016;38:3–15.
  • Gavine PR, Mooney L, Kilgour E, et al. AZD4547: an orally bioavailable, potent, and selective inhibitor of the fibroblast growth factor receptor tyrosine kinase family. Cancer Res. 2012;72:2045–2056.
  • Guagnano V, Furet P, Spanka C, et al. Discovery of 3-(2,6-Dichloro-3,5-dimethoxy-phenyl)-1-{6-[4-(4-ethyl- piperazin-1-yl)-phenylamino]-pyrimidin-4-yl}-1-methyl-urea (NVP-BGJ398), A potent and selective inhibitor of the fibroblast growth factor receptor family of receptor tyrosine kinase. J Med Chem. 2011;54:7066–7083.
  • Mohammadi M, Froum S, Hamby JM, et al. Crystal structure of an angiogenesis inhibitor bound to the FGF receptor tyrosine kinase domain. Embo J. 1998;17:5896–5904.
  • Zhao G, Li W-Y, Chen D, et al. A novel, selective inhibitor of fibroblast growth factor receptors that shows a potent broad spectrum of antitumor activity in several tumor xenograft models. Mol Cancer Ther. 2011;10:2200–2210.
  • Ebiike H, Taka N, Matsushita M, et al. Discovery of [5-amino-1-(2-methyl-3H-benzimidazol-5-yl)pyrazol-4-yl]-(1H-indol-2-yl)methanone (CH5183284/Debio 1347), an orally available and selective Fibroblast Growth Factor Receptor (FGFR) inhibitor. J Med Chem. 2016;59:10586–10600.
  • Futami T, Okada H, Kihara R, et al. ASP5878, a Novel Inhibitor of FGFR1, 2, 3, and 4, Inhibits the Growth of FGF19-Expressing Hepatocellular Carcinoma. Mol Cancer Ther. 2017;16:68–75.
  • Kameda M Astellas pharma inc., Kotobuki pharmaceutical co. Nitrogen-containing aromatic heterocyclic compounds. WO2013129369. 2013.
  • Collin MP, Lobell M, Hübsch W, et al. Discovery of Rogaratinib (BAY 1163877): a pan-FGFR Inhibitor. ChemMedChem. 2018;13:437–445.
  • BROHM D, HEROULT M, COLLIN M-P, et al. Bayer pharma aktiengesellschaft disubstituted benzothienyl-pyrrolotriazines and their use as Fgfr kinase inhibitors. WO2013087578. 2013.
  • Nogova L, Sequist LV, Garcia JMP, et al. Evaluation of BGJ398, a Fibroblast growth factor receptor 1-3 kinase inhibitor, in patientswith advanced solid tumors harboring genetic alterations in fibroblast growth factor receptors: results of a global phase I, dose-escalation and dose-expansion stud. J Clin Oncol. 2017;35:157–165.
  • Tabernero J, Bahleda R, Dienstmann R, et al. Phase I dose-escalation study of JNJ-42756493, an oral pan-fibroblast growth factor receptor inhibitor, in patients with advanced solid tumors. J Clin Oncol. 2015;33:3401–3408.
  • Perera TPS, Jovcheva E, Mevellec L, et al. Discovery and pharmacological characterization of JNJ-42756493 (Erdafitinib), a functionally selective small-molecule FGFR family inhibitor. Mol Cancer Ther. 2017;16:1010–1020.
  • Markham A. Erdafitinib: first Global Approval. Drugs. 2019;79:1017–1021.
  • Zuccotto F, Ardini E, Casale E, et al. Through the “ gatekeeper door ”: exploiting the active kinase conformation. J Med Chem. 2010;53:2681–2694.
  • Sohl CD, Ryan MR, Luo B, et al. Illuminating the molecular,mechanisms of tyrosine kinase inhibitor resistance for the FGFR1 gatekeeper mutation: the Achilles’ heel of targeted therapy. ACS Chem Biol. 2015;10:1319–1329.
  • Chell V, Balmanno K, Little AS, et al. Tumour cell responses to new fibroblast growth factor receptor tyrosine kinase inhibitors and identification of a gatekeeper mutation in FGFR3 as a mechanism of acquired resistance. Oncogene. 2012;32:3059–3070.
  • Byron SA, Chen H, Wortmann A, et al. The N550K/H mutations in FGFR2 confer differential resistance to PD173074, dovitinib and ponatinib ATP-competitive inhibitors. Neoplasia. 2013;15:975–988.
  • Zhou W, Hur W, McDermott U, et al. A Structure-Guided Approach to Creating Covalent FGFR Inhibitors. Chem Biol. 2010;17:285–295.
  • Azam M, Seeliger MA, Gray NS, et al. Activation of tyrosine kinases by mutation of the gatekeeper threonine. Nat Struct Mol Biol. 2008;15:1109–1118.
  • Ryan MR, Christal D, Sohl BL, et al. The FGFR1 V561M Gatekeeper mutation drives AZD4547 resistance through STAT3 activation and EMT. Mol Cancer Res. 2018. DOI:10.1158/1541-7786.MCR-18-0429.
  • Tan L, Wang J, Tanizaki J, et al. Development of covalent inhibitors that can overcome resistance to first-generation FGFR kinase inhibitors. Proc Natl Acad Sci. 2014;111:E4869–E4877.
  • Sootome H, Fujioka Y, Miura A, et al. Abstract A271: TAS-120, an irreversible FGFR inhibitor, was effective in tumors harboring FGFR mutations, refractory or resistant to ATP competitive inhibitors. Mol Cancer Ther. 2013;12:A271 LP–A271.
  • Sagara T, Ito S, Otsuki S, et al. Taiho pharmaceutical Co. 3,5-disubstituted alkynylbenzene compound and salt thereof. WO2013108809. 2013.
  • Hagel M, Miduturu C, Sheets M, et al. First selective small molecule inhibitor of FGFR4 for the treatment of hepatocellular Carcinomas with an activated FGFR4 signaling pathway. Cancer Discov. 2015;5:424–437.
  • Bifulco NJ, Brooijmans N, Hodous BL, et al. Blueprint medicines corporation. Inhibitors of the fibroblast growth factor receptor. WO2014011900. 2014.
  • Packer LM, Pollock PM. Paralog-specifi c kinase inhibition of FGFR4 : adding to the arsenal of anti-FGFR agents. Cancer Discov. 2015;5:355–357.
  • Geng M, Liu L, Jiang L, et al. Hanghai Haihe pharmaceutical ltd. Shanghai institute of materia medica, chinese academy of sciences. indazole compounds as fgfr kinase inhibitor, preparation and use thereof. WO2016026445. 2016.
  • Zhao B, Li Y, Xu P, et al. Discovery of substituted 1H-pyrazolo[3,4-b]pyridine derivatives as potent and selective FGFR kinase inhibitors. ACS Med Chem Lett. 2016;7:629–634.
  • McBride CM, Renhowe PA, Heise C, et al. Design and structure-activity relationship of 3-benzimidazol-2-yl-1H-indazoles as inhibitors of receptor tyrosine kinases. Bioorg Med Chem Lett. 2006;16:3595–3599.
  • Duan W, Geng M, Yan W, et al. Shanghai institute of materia medica, Chinese academy of sciences. Method for preparing indazole compound and use thereof. WO2017008708. 2017.
  • Yan W, Wang X, Dai Y, et al. Discovery of 3-(5′-substituted)-benzimidazole-5-(1-(3,5-dichloropyridin-4-yl)ethoxy)-1H-indazoles as potent fibroblast growth factor receptor inhibitors: design, synthesis, and biological evaluation. J Med Chem. 2016;59:6690–6708.
  • Liu H, Geng M, Zhu W, et al. Shanghai institute of materia medica, Chinese academy of sciences. Pyrazolophenyl-pyridine compound, pharmaceutical composition comprising same, and use thereof. WO2016188481. 2016.
  • Zhu W, Chen H, Wang Y, et al. Design, synthesis, and pharmacological evaluation of novel multisubstituted pyridin-3-amine derivatives as multitargeted protein kinase inhibitors for the treatment of non-small cell lung cancer. J Med Chem. 2017;60:6018–6035.
  • Zhang A, Geng M, Xing L, et al. Institute of materia medica, chinese academy of sciences. Substituted amino six-membered nitric heterocyclic ring compound and preparation and use thereof. WO2017140269. 2017.
  • Setsuo F, Toshimi O, Keigo T, et al. Eisai R&D management Co., Ltd Monocyclic pyridine derivative. US20140235614. 2014.
  • Wei M, Peng X, Xing L, et al. Design, synthesis and biological evaluation of a series of novel 2-benzamide-4-(6-oxy-N-methyl-1-naphthamide)-pyridine derivatives as potent fibroblast growth factor receptor (FGFR) inhibitors. Eur J Med Chem. 2018;154:9–28.
  • Jiang XF, Dai Y, Peng X, et al. SOMCL-085, a novel multi-targeted FGFR inhibitor, displays potent anticancer activity in FGFR-addicted human cancer models. Acta Pharmacol Sin. 2018;39:243–250.
  • Xu X, Wang J, Ding L et al. Betta pharmaceuticals ltd. Fgfr inhibitor and application thereof. WO2018153373. 2018.
  • Zhang H, Liu S Hangzhou innogate pharma ltd. Heterocyclic compound used as FGFR inhibitor: WO2017118438. 2017.
  • Yen Y, J-P L, Chen C-H Taipei medical university. Chlorobenzene substituted azaaryl compounds. WO2017015400. 2017.
  • Chen C, Liu Y, Pan S, et al. Trichlorobenzene-substituted azaaryl compounds as novel FGFR inhibitors exhibiting potent antitumor activity in bladder cancer cells in vitro and in vivo. Oncotarget. 2016;7:26374–26387.
  • Chen C, Changou CA, Hsieh T, et al. Dual inhibition of PIK3C3 and FGFR as a new therapeutic approach to treat bladder cancer. Clin Cancer Res. 2018;24:1176–1190.
  • Greff Z, Kéri G, Örfi L, et al. Vichem chemie kutató kft. Benzo[b]thiophene derivatives and their use for the inhibition of fibroblast growth factor receptor kinases (FGFRs) for the use of neo- and hyperplasia therapies. WO2017153789. 2017.
  • Sootome H Taiho pharmaceutical ltd. Therapeutic agent for FGFR inhibitor-resistant cancer. WO2015008844. 2015.
  • Goyal L, Shi L, Liu LY, et al. TAS-120 overcomes resistance to ATP-competitive FGFR inhibitors in patients with FGFR2 fusion-positive intrahepatic cholangiocarcinoma. Cancer Discov. 2019;9:1064–1079:CD-19-0182.
  • Kalyukina M, Yosaatmadja Y, Middleditch MJ, et al. TAS‐120 cancer target binding: defining reactivity and revealing the first Fibroblast Growth Factor Receptor 1 (FGFR1) irreversible structure. ChemMedChem. 2019;14:494–500.
  • Zhang Y, Wang Y, Chen L, et al. Medshine discovery Inc. FGFR inhibitors. WO2018121650. 2018.
  • Kong NX, Zhou C, Chen X. Guangzhou innocare pharma, ltd. Heterocyclic compound as FGFR inhibitor: WO2018028438. 2018.
  • Xiangyang C, Yiagxiang G, Xianglong N. Beijing innocare pharma. Alkynyl-substituted heterocyclic compound, preparation method thereof and medical use thereof. US20190210997. 2019.
  • Duan W, Geng M, Wang Y, et al. Shanghai institute of materia medica, chinese academy of sciences. New compound having fgfr inhibitory activity and preparation and application thereof. WO2017215485. 2017.
  • Wang Y, Dai Y, Wu X, et al. Discovery and development of a series of pyrazolo[3,4-d]pyridazinone compounds as the novel covalent fibroblast growth factor receptor inhibitors by the rational drug design. J Med Chem. 2019;62:7473–7488.
  • Wang Y, Li L, Fan J, et al. Discovery of potent irreversible Pan-Fibroblast Growth Factor Receptor (FGFR) inhibitors. J Med Chem. 2018;61:9085–9104.
  • Verner E, Brameld KA, Biopharma P. Quinolone derivatives as fibroblast growth factor receptor inhibitors. WO2015120049. 2015.
  • Brameld KA, Owens TD, Verner E, et al. Discovery of the irreversible covalent FGFR inhibitor 8‑(3-(4- Acryloylpiperazin-1-yl)propyl)-6-(2,6-dichloro-3,5-dimethoxyphenyl)- 2-(methylamino)pyrido[2,3‑d]pyrimidin-7(8H)‑one (PRN1371) for the treatment of solid tumors. J Med Chem. 2017;60:6516–6527.
  • Venetsanakos E, Brameld KA, Phan VT, et al. The irreversible covalent fibroblast growth factor receptor inhibitor PRN1371 exhibits sustained inhibition of FGFR after drug clearance. Mol Cancer Ther. 2017;16:2668–2677.
  • Bradshaw JM, Mcfarland JM, Paavilainen VO, et al. Prolonged and tunable residence time using reversible covalent kinase inhibitor. Nat Chem Biol. 2015;11:525.
  • Brameld KA, Verner E. Principia Biopharma Inc. Quinolone derivatives as fibroblast growth factor receptor inhibitors. WO2016191172. 2016.
  • Patterson AV, Smaill JB, Ashoorzadeh A, et al. Auckland uniservices limited, Guangzhou institut. FGFR kinase inhibitors and pharmaceutical uses. WO2018160076. 2018.
  • WU F. Nanjing transthera biosciences. Fibroblast growth factor receptor inhibitor and use thereof. WO2019029541. 2019.
  • Li X, Guise CP, Taghipouran R, et al. 2-Oxo-3, 4-dihydropyrimido[4, 5-d]pyrimidinyl derivatives as new irreversible pan fibroblast growth factor receptor (FGFR) inhibitors. Eur J Med Chem. 2017;135:531–543.
  • French DM, Lin BC, Wang M, et al. Targeting FGFR4 inhibits hepatocellular carcinoma in preclinical mouse models. PLoS One. 2012;7:1–12.
  • Quintanal-Villalonga A, Ferrer I, Molina-Pinelo S, et al. A patent review of FGFR4 selective inhibition in cancer (2007-2018). Expert Opin Ther Pat. 2007;29:429–438.
  • Fairhurst RA, Knoepfel T, Leblanc C, et al. Approaches to selective fibroblast growth factor receptor 4 inhibition through targeting the ATP-pocket middle-hinge region. Medchemcomm. 2017;8:1604–1613.
  • Zhao X, Xu F, Dominguez NP, et al. FGFR4 provides the conduit to facilitate FGF19 signaling in breast cancer progression. Mol Carcinog. 2018;57:1616–1625.
  • Bifulco NJ, Dipietro LV, Hodous BL, et al. Blueprint medicines corporation. Inhibitors of the fibroblast growth factor receptor. WO2015061572. 2015.
  • D’Agostino LA, Sjin RTT, Niu D, et al. Celgene avilomics research, Sanofi. Heteroaryl compounds and uses thereof. WO2014144737. 2014.
  • Lee MS, Byun EY, Kim JS, et al. Hanmi pharmaceutical ltd. Novel heterocyclic derivative compound and use thereof. WO2018004258. 2018.
  • Lu L, Wu L, Shen B, et al. Incyte corporation. Bicyclic heterocycles as FGFR4 inhibitors. WO2016134294. 2016.
  • Reynolds D, Hao M, Wang J, et al. Eisai R&D management ltd. Fgfr4 inhibitors. WO2015057963. 2015.
  • Reynolds D, Hao M, Wang J, et al. Eisai R&D management ltd. Pyrimidine FGFR4 inhibitors. WO2015057938. 2015.
  • Reynolds D, Hao M, Wang J, et al. Eisai R&D management ltd. Fgfr4 inhibitors. WO2016164703. 2016.
  • Joshi JJ, Coffey H, Corcoran E, et al. H3B-6527 is a potent and selective inhibitor of FGFR4 in FGF19-driven hepatocellular Carcinoma. Cancer Res. 2017;77:6999–7014.
  • Wang Y, Chen Z, Dai M, et al. Discovery and optimization of selective FGFR4 inhibitors via scaffold hopping. Bioorg Med Chem Lett. 2017;27:2420–2423.
  • Chen L, Guan D, Bai H, et al. Zhejiang Hisun Pharmaceutical Co. Pyrimidine derivative, method for preparing same and use thereof in medicine. WO2017198221. 2017.
  • Chen Z, Long C, Zhang Y, et al. Guangdong Zhongsheng pharmaceutical ltd, medshine discovery Inc. FGFR4 inhibitor and preparation method and use thereof. WO2018090973. 2018.
  • Mo C, Zhang Z, Guise CP, et al. 2‑Aminopyrimidine derivatives as new selective fibroblast growth factor receptor 4 (FGFR4) inhibitors. ACS Med Chem Lett. 2017;8:543–548.
  • Shao N, Yuan H, Wang D, et al. Bioardis. Aromatic ether derivative, preparation method therefor, and medical applications thereof. WO2018072707. 2018.
  • Knoepfel T, Furet P, Mah R, et al. 2-Formylpyridyl ureas as highly selective reversible-covalent inhibitors of fibroblast growth factor receptor 4. ACS Med Chem Lett. 2018;9:215–220.
  • Liu J, Zhang H Shanghai Zheye Biotechnology llc. Compound for selectively inhibiting kinase and use thereof. WO2018121774. 2018.
  • Li X, He L, Chen L, et al. Jiangsu Hansoh Pharmaceutical. FGFR4 inhibitor and prepation method therefor. WO2019085860. 2019.
  • Zhou C, Zheng C, Zheng Z. Nanjing innocare pharma. Heterocyclic compounds used as FGFR inhibitors. US20190144427. 2019.
  • Knight ZA, Shokat KM. Features of selective kinase inhibitors. Chem Biol. 2005;12:621–637.
  • Jackson PA, Widen JC, Harki DA, et al. Covalent modifiers: A chemical perspective on the reactivity of α,β-unsaturated carbonyls with thiols via hetero-michael addition reactions. J Med Chem. 2017;60:839–885.
  • Fumarola C, Bozza N, Castelli R, et al. Expanding the arsenal of FGFR inhibitors: a novel chloroacetamide derivative as a new irreversible agent with anti-proliferative activity against FGFR1-amplified lung cancer cell lines. Front Oncol. 2019;9:179.
  • Blackwell C, Sherk C, Fricko M, et al. Inhibition of FGF/FGFR autocrine signaling in mesothelioma with the FGF ligand trap, FP-1039/GSK3052230. Oncotarget. 2016;7:39861–39871.
  • Ronca R, Giacomini A, Di Salle E, et al. Long-pentraxin 3 derivative as a small-molecule FGF trap for cancer therapy. Cancer Cell. 2015;28:225–239.
  • Herbert C, Schieborr U, Saxena K, et al. Molecular mechanism of SSR128129E, an extracellularly acting, small-molecule, allosteric inhibitor of FGF receptor signaling. Cancer Cell. 2013;23:489–501.
  • Weiner GJ. Building better monoclonal antibody-based therapeutics. Nat Rev Cancer. 2015;15:361.
  • Tejani MA, Cheung E, Eisenberg PD, et al. Phase I results from the phase 1/3 FIGHT study evaluating bemarituzumab and mFOLFOX6 in advanced gastric/GEJ cancer (GC). J Clin Oncol. 2019;37: 91–91.

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