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.
A blog highlighting recent publications in the area of covalent modification of proteins, particularly relating to covalent-modifier drugs. @CovalentMod on Twitter, @covalentmod@mstdn.science on Mastodon, and @covalentmod.bsky.social on BlueSky
Thursday, October 7, 2021
DrugMap: A quantitative pan-cancer analysis of cysteine ligandability
Mariko Takahashi, Harrison B. Chong,Siwen Zhang, Tzu-Yi Yang,Matthew J. Lazarov,Stefan Harry,Michelle Maynard, Brendan Hilbert,Ryan D. White...
-
Linqi Cheng Yixian Wang, Yiming Guo, Sophie S. Zhang Han Xiao C ell Chemical Biology, 2024 Volume 31, 3, 428 - 445 https://doi.org/10.10...
-
Cravatt, B.; Njomen, E.; Hayward, R.; DeMeester, K.; Ogasawara, D.; Dix, M.; Nguyen, T.; Ashby, P.; Simon, G.; Schreiber, S.; Melillo, B. C...
-
Grob, N. M.; Remarcik, C.; Rössler, S. L.; Wong, J. Y. K.; Wang, J. C. K.; Tao, J.; Smith, C. L.; Loas, A.; Buchwald, S. L.; Eaton, D. L.; P...