Selective and noncovalent targeting of RAS mutants for inhibition and degradation

Kai Wen Teng; Steven T. Tsai; Takamitsu Hattori; Carmine Fedele; Akiko Koide; Chao Yang; Xuben Hou; Yingkai Zhang; Benjamin G. Neel; John P. O’Bryan; Shohei Koide

doi:10.1038/s41467-021-22969-5

Nature Communications (May 2021)

Selective and noncovalent targeting of RAS mutants for inhibition and degradation

Kai Wen Teng,
Steven T. Tsai,
Takamitsu Hattori,
Carmine Fedele,
Akiko Koide,
Chao Yang,
Xuben Hou,
Yingkai Zhang,
Benjamin G. Neel,
John P. O’Bryan,
Shohei Koide

Affiliations

Kai Wen Teng: Perlmutter Cancer Center, New York University Langone Health
Steven T. Tsai: Perlmutter Cancer Center, New York University Langone Health
Takamitsu Hattori: Perlmutter Cancer Center, New York University Langone Health
Carmine Fedele: Perlmutter Cancer Center, New York University Langone Health
Akiko Koide: Perlmutter Cancer Center, New York University Langone Health
Chao Yang: Department of Chemistry, New York University
Xuben Hou: Department of Chemistry, New York University
Yingkai Zhang: Department of Chemistry, New York University
Benjamin G. Neel: Perlmutter Cancer Center, New York University Langone Health
John P. O’Bryan: Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina
Shohei Koide: Perlmutter Cancer Center, New York University Langone Health

DOI: https://doi.org/10.1038/s41467-021-22969-5
Journal volume & issue: Vol. 12, no. 1
pp. 1 – 13

Abstract

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Most oncogenic RAS mutants remain undruggable. Here, the authors developed monobodies that selectively recognize the active state of KRAS(G12V) and KRAS(G12C) and demonstrated their utility in inhibiting RAS functions through inhibition and degradation.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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