7VJL

The crystal structure of FGFR4 kinase domain in complex with N-(5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)-7-(2,2,2-trifluoroacetyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide

Summary for 7VJL

• Entry DOI: 10.2210/pdb7vjl/pdb
• Descriptor: Fibroblast growth factor receptor 4, N-[5-(aminomethyl)-4-(2-methoxyethylamino)pyridin-2-yl]-7-[2,2,2-tris(fluoranyl)ethanoyl]-3,4-dihydro-2H-1,8-naphthyridine-1-carboxamide (2 entities in total)
• Functional Keywords: fgfr4, transferase inhibitor, transferase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 68508.87

Authors

Zhang, Z.M.,Wang, Y.J. (deposition date: 2021-09-28, release date: 2022-02-23, Last modification date: 2024-11-13)

Primary citation

Zhang, Z.,Wang, Y.,Chen, X.,Song, X.,Tu, Z.,Chen, Y.,Zhang, Z.,Ding, K.
Characterization of an aromatic trifluoromethyl ketone as a new warhead for covalently reversible kinase inhibitor design.
Bioorg.Med.Chem., 50:116457-116457, 2021

PubMed Abstract: 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 successfully designed and synthesized by utilizing this new warhead. The binding mode of a representative inhibitor was fully characterized by using multiple technologies including MALDI-TOF mass spectrometry, dialysis assay and X-ray crystallographic studies etc. This functional group was also successfully applied to discovery of a new JAK3 inhibitor, suggesting its potential application in designing other kinase inhibitors.

PubMed: 34670167
DOI: 10.1016/j.bmc.2021.116457

Experimental method

X-RAY DIFFRACTION (2.90017299719 Å)