- Discovery of Roblitinib (FGF401) as a Reversible-Covalent Inhibitor of the Kinase Activity of Fibroblast Growth Factor Receptor 4
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FGF19 signaling through the FGFR4/β-klotho receptor complex has been shown to be a key driver of growth and survival in a subset of hepatocellular carcinomas, making selective FGFR4 inhibition an attractive treatment opportunity. A kinome-wide sequence al
- Fairhurst, Robin A.,Knoepfel, Thomas,Buschmann, Nicole,Leblanc, Catherine,Mah, Robert,Todorov, Milen,Nimsgern, Pierre,Ripoche, Sebastien,Niklaus, Michel,Warin, Nicolas,Luu, Van Huy,Madoerin, Mario,Wirth, Jasmin,Graus-Porta, Diana,Weiss, Andreas,Kiffe, Michael,Wartmann, Markus,Kinyamu-Akunda, Jacqueline,Sterker, Dario,Stamm, Christelle,Adler, Flavia,Buhles, Alexandra,Schadt, Heiko,Couttet, Philippe,Blank, Jutta,Galuba, Inga,Trappe, J?rg,Voshol, Johannes,Ostermann, Nils,Zou, Chao,Berghausen, J?rg,Del Rio Espinola, Alberto,Jahnke, Wolfgang,Furet, Pascal
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- High-selectivity fibroblast growth factor receptor inhibitor and application
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The invention discloses a high-selectivity fibroblast growth factor receptor inhibitor and application, and particularly relates to a compound shown in a formula (I) or a pharmaceutically acceptable salt, a solvate, a geometric isomer, a stereoisomer, a tautomer and any mixture thereof. The compound shown in the formula (I) or the pharmaceutically acceptable salt, the solvate and the pharmaceutical composition thereof can be applied to prevention or treatment of diseases related to FGFR4 activity or overexpression, and can also be combined with other medicines to be used for treating various related diseases, especially for treating various cancers, wherein the cancers may be liver cancer, lung cancer, gastric cancer, breast cancer, ovarian cancer, prostate cancer, renal cell carcinoma, skin cancer, colon cancer, bile duct cancer, glioma or sarcoma.
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- Characterization of an aromatic trifluoromethyl ketone as a new warhead for covalently reversible kinase inhibitor design
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An aromatic trifluoromethyl ketone moiety was characterized as a new warhead for covalently reversible kinase inhibitor design to target the non-catalytic cysteine residue. Potent and selective covalently reversible inhibitors of FGFR4 kinase were success
- Zhang, Zhen,Wang, Yongjin,Chen, Xiaojuan,Song, Xiaojuan,Tu, Zhengchao,Chen, Yongheng,Zhang, Zhimin,Ding, Ke
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- FGFR4 INHIBITOR, PREPARATION METHOD THEREFOR, AND APPLICATIONS THEREOF
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The present invention relates to an FGFR4 inhibitor having a structure represented by formula (I), preparation method therefor, and applications thereof. A series of compounds represented by formula (I) in the present invention have a very-strong inhibiti
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- FGFR4 INHIBITOR AND PREPARATION METHOD AND USE THEREOF
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Provided are an FGFR4 inhibitor with the structure of formula (I) and a preparation method and use thereof. The series of compounds of formula (I) have a very strong inhibitory effect on the FGFR4 kinase activity, and have a very high selectivity; and sam
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- Novel 7-formyl-naphthyridyl-ureas derivatives as potential selective FGFR4 inhibitors: Design, synthesis, and biological activity studies
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Total twenty-five 7-formyl-naphthyridyl-urea derivatives were designed, synthesized and evaluated for their inhibition of FGFR4 kinase and antitumor activity. The pharmacological data indicated that most of the tested compounds showed high selectivity towards FGFR4 kinase and could significantly inhibit FGFR4 and the tumor cells lines with the high expression of FGFR4. In particular, compounds 6f, 6g, 6h, 6l, 6m and 6s showed a good performance in pharmacokinetic tests. When tested in mice, the representative compound 6f was found to have good pharmacokinetic parameters, low toxicity, and better tumor inhibiting activity in vivo.
- Sun, Chang'an,Fang, Lei,Zhang, Xiaobing,Gao, Peng,Gou, Shaohua
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p. 1932 - 1941
(2019/04/25)
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- 2-Formylpyridyl Ureas as Highly Selective Reversible-Covalent Inhibitors of Fibroblast Growth Factor Receptor 4
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As part of a project to identify FGFR4 selective inhibitors, scaffold morphing of a 2-formylquinoline amide hit identified series of 2-formylpyridine ureas (2-FPUs) with improved potency and physicochemical properties. In particular, tetrahydronaphthyridi
- Knoepfel, Thomas,Furet, Pascal,Mah, Robert,Buschmann, Nicole,Leblanc, Catherine,Ripoche, Sebastien,Graus-Porta, Diana,Wartmann, Markus,Galuba, Inga,Fairhurst, Robin A.
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supporting information
p. 215 - 220
(2018/03/21)
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- PHARMACEUTICAL COMBINATIONS
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A pharmaceutical combination comprising N-(5-cyano-4-((2-methoxyethyl)amino)pyridin- 2-yl)-7-formyl-6-((4-methyl-2-oxopiperazin-1-yl)methyl)-3,4-dihydro-1,8-naphthyridine- 1(2H)-carboxamide, or a pharmaceutically acceptable salt thereof, and at least one active ingredient, as defined herein, or a pharmaceutically acceptable salt thereof, and optionally a pharmaceutically acceptable carrier, for simultaneous or sequential administration; the uses of such combination in the treatment of proliferative diseases; and methods of treating a subject suffering from a proliferative disease comprising administering a therapeutically effective amount of such combination.
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- PARTICLES OF N-(5-CYANO-4-((2-METHOXYETHYL)AMINO)PYRIDIN-2-YL)-7-FORMYL-6-((4-METHYL-2- OXOPIPERAZIN-1-YL)METHYL)-3,4-DIHYDRO-1,8-NAPHTHYRIDINE-1(2H)-CARBOXAMIDE
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The present invention relates to particles of N-(5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)-7- formyl-6-((4-methyl-2-oxopiperazin-1-yl)methyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide, to a process of making said particles, to pharmaceutical compositions comprising said particles and to method of treating cancers using said pharmaceutical compositions.
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- FORMYLATED N-HETEROCYCLIC DERIVATIVES AS FGFR4 INHIBITORS
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The present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof; (I) a method for manufacturing said compound, and its therapeutic uses. The present invention further provides a combination of pharmacologically activ
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- Ring-fused bicyclic pyridyl derivatives as FGFR4 inhibitors
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The present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof; a method for manufacturing said compound, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition comprising said compound.
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- RING-FUSED BICYCLIC PYRIDYL DERIVATIVES AS FGFR4 INHIBITORS
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The present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof; a method for manufacturing said compound, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition comprising said compound.
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