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From KRASG12D to Pan-KRAS Inhibitors─A Journey Enabled by Synthetic Innovation and Structure-Based Drug Design
Xiaoshen Ma1, David L Sloman1, Timothy J Henderson1
1Department of Discovery Chemistry, Merck & Co., Inc., 33 Ave. Louis Pasteur, Boston 02215, Massachusetts, United States.
Abstract:
KRAS, a significant oncology target, has been challenging to develop drugs for until recent discoveries of KRASG12C mutant-specific covalent inhibitors, including MK-1084. This article describes efforts toward the discovery of KRASG12D mutant-specific inhibitors and how synthetic innovations and structure-based drug design were utilized to facilitate the discovery of pan-KRAS inhibitors.
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