Related Experiment Video
Updated: Mar 26, 2026
Author Spotlight: Integrating BRET-Based Assays and Rare Mutation Analysis to Decipher RAF Kinase Regulation in Live Cells
Published on: March 1, 2024
Optimization of tetrahydronaphthalene inhibitors of Raf with selectivity over hERG
Shih-Chung Huang1, Sharmila Adhikari1, Roushan Afroze1
1Takeda Pharmaceuticals International Co. 40 Landsdowne Street, Cambridge, MA 02139, United States.
Abstract:
Investigations of a biaryl ether scaffold identified tetrahydronaphthalene Raf inhibitors with good in vivo activity; however these compounds had affinity toward the hERG potassium channel. Herein we describe our work to eliminate this hERG activity via alteration of the substituents on the benzoic amide functionality. The resulting compounds have improved selectivity against the hERG channel, good pharmacokinetic properties and potently inhibit the Raf pathway in vivo.
More Related Videos
07:49Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
Published on: July 17, 2019
10:33Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
Published on: October 26, 2015
