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Kevan M. Shokat

The chemist whose lab found the hidden pocket in KRAS G12C that made the 'undruggable' target druggable.

Kevan Shokat is a chemical biologist. His 2013 discovery of covalent inhibitors binding the switch-II pocket of KRAS G12C opened the path to sotorasib and adagrasib. Also known for the bump-hole approach to kinase chemical genetics.

Role
Professor of Cellular and Molecular Pharmacology, UCSF; Investigator, Howard Hughes Medical Institute
Specialisms
Chemical biologyKRASKinase inhibitors

Papers

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TitleJournalYear
K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactionsNature2013
A chemical switch for inhibitor-sensitive alleles of any protein kinaseNature2000

Key papers

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basicNature 2013
Ostrem and Shokat: the hidden pocket that made KRAS G12C druggable

The most frequently mutated oncogene in cancer stopped being undruggable, and patients with KRAS G12C lung and bowel cancers now have targeted pills. The approach, exploiting a mutation-created chemical handle and an inactive-state pocket, has become a template for other hard targets.

Connected

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cancers

3
Colorectal cancerNon-small-cell lung cancerPancreatic ductal adenocarcinoma

technologies

2
KRAS & RAS inhibitorsSmall-molecule kinase inhibitors

targets

1
KRAS

drugs

2
ApprovedSmall-molecule inhibitor (KRAS G12C)
Adagrasib · Krazati
ApprovedSmall-molecule inhibitor (KRAS G12C)
Sotorasib · Lumakras

institutions

1
UCSF Helen Diller Family Comprehensive Cancer Center

key papers

1
Ostrem and Shokat: the hidden pocket that made KRAS G12C druggable