Hitting KRAS When It’s Down

Ronen Gabizon; Nir London

doi:10.1021/acs.jmedchem.0c00785

Hitting KRAS When It’s Down

Ronen Gabizon, Nir London

Department of Molecular Chemistry and Materials Science

Weizmann Institute of Science

Research output: Contribution to journal › Article › peer-review

Abstract

KRAS, one of the most prevalent oncogenes and sought-after anticancer targets, has eluded chemists for decades until an irreversible covalent strategy targeting a specific mutation (G12C) paved the way for the first KRAS inhibitors to reach the clinic. MRTX849 is one such clinical candidate with promising initial results in patients harboring the mutation. The impressive optimization story of MRTX849 highlights challenges and solutions in the development of covalent drugs, including the use of an α-fluoroacrylamide electrophile.

Original language	English
Pages (from-to)	6677-6678
Number of pages	2
Journal	Journal of Medicinal Chemistry
Volume	63
Issue number	13
DOIs	https://doi.org/10.1021/acs.jmedchem.0c00785
State	Published - 9 Jul 2020

All Science Journal Classification (ASJC) codes

Molecular Medicine
Drug Discovery

Access to Document

10.1021/acs.jmedchem.0c00785License: CC BY

Cite this

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AB - KRAS, one of the most prevalent oncogenes and sought-after anticancer targets, has eluded chemists for decades until an irreversible covalent strategy targeting a specific mutation (G12C) paved the way for the first KRAS inhibitors to reach the clinic. MRTX849 is one such clinical candidate with promising initial results in patients harboring the mutation. The impressive optimization story of MRTX849 highlights challenges and solutions in the development of covalent drugs, including the use of an α-fluoroacrylamide electrophile.

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DO - 10.1021/acs.jmedchem.0c00785

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