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Review
. 2021 Jun:62:101-108.
doi: 10.1016/j.cbpa.2021.02.010. Epub 2021 Apr 7.

Targeting mutant KRAS

Daniel A Erlanson  1 , Kevin R Webster  2
Affiliations
Review

Targeting mutant KRAS

Daniel A Erlanson et al. Curr Opin Chem Biol. 2021 Jun.

Abstract

The protein KRAS has for decades been considered a holy grail of cancer drug discovery. For most of that time, it has also been considered undruggable. Since 2018, five compounds have entered the clinic targeting a single mutant form of KRAS, G12C. Here, we review each of these compounds along with additional approaches to targeting this and other mutants. Remaining challenges include expanding the identification of inhibitors to a broader range of known mutants and to conformations of the protein more likely to avoid development of resistance.

Keywords: Covalent drugs; Fragment-based drug discovery; G12C; G12D; KRAS; Precision oncology.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Daniel Erlanson and Kevin Webster are both employees and shareholders of Frontier Medicines, and Daniel Erlanson is a shareholder of Carmot Therapeutics.

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