An article Rigidification Dramatically Improves Inhibitor Selectivity for RAF Kinases WOS:000475543200012 published article about MULTIKINASE INHIBITOR; DISCOVERY; RESISTANCE; SORAFENIB; MUTATIONS; PATHWAY in [Assadieskandar, Amir; Yu, Caiqun; Zhang, Chao] Univ Southern Calif, Loker Hydrocarbon Res Inst, Los Angeles, CA 90089 USA; [Assadieskandar, Amir; Yu, Caiqun; Zhang, Chao] Univ Southern Calif, Dept Chem, Los Angeles, CA 90089 USA; [Zhang, Chao] Univ Southern Calif, USG Norris Comprehens Canc Ctr, Los Angeles, CA 90089 USA; [Maisonneuve, Pierre; Sicheri, Frank] Sinai Hlth Syst, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada; [Sicheri, Frank] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada; [Sicheri, Frank] Univ Toronto, Dept Biochem, Toronto, ON, Canada; [Kunnov, Igor] Cornell Univ, NE CAT, Dept Chem & Chem Biol, Argonne, IL 60439 USA in 2019, Cited 24. The Name is 3-(Trifluoromethyl)phenol. Through research, I have a further understanding and discovery of 98-17-9. Recommanded Product: 98-17-9
One effective means to achieve inhibitor specificity for RAF kinases, an important family of cancer drug targets, has been to target the monomeric inactive state conformation of the kinase domain, which, unlike most other kinases, can accommodate sulfonamide-containing drugs such as vemurafenib and dabrafenib because of the presence of a unique pocket specific to inactive RAF kinases. We previously reported an alternate strategy whereby rigidification of a nonselective pyrazolo[3,4-d]pyrimidine-based inhibitor through ring closure afforded moderate but appreciable increases in selectivity for RAF kinases. Here, we show that a further application of the rigidification strategy to a different pyrazolopyrimidine-based scaffold dramatically improved selectivity for RAF kinases. Crystal structure analysis confirmed our inhibitor design hypothesis revealing that 21 engages an active-like state conformation of BRAF normally associated with poorly discriminating inhibitors. When screened against a panel of distinct cancer cell lines, the optimized inhibitor 21 primarily inhibited the proliferation of the expected BRAF(V600E)-harboring cell lines consistent with its kinome selectivity profile. These results suggest that rigidification could be a general and powerful strategy for enhancing inhibitor selectivity against protein kinases, which may open up therapeutic opportunities not afforded by other approaches.
Recommanded Product: 98-17-9. About 3-(Trifluoromethyl)phenol, If you have any questions, you can contact Assadieskandar, A; Yu, CQ; Maisonneuve, P; Kunnov, I; Sicheri, F; Zhang, C or concate me.
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Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
,Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles