Work

KRAS inhibitors: going noncovalent

Year: 2022

Type: article

Abstract: KRASG12D is the most frequent KRAS mutation in human cancer with particularly high frequencies in pancreatic and colorectal cancer. Informed by the structure of the KRASG12C inhibitor adagrasib, Hallin et al. have now, through multiple rounds of structure‐based drug design, identified and validated a potent, selective, and noncovalent KRASG12D inhibitor, MRTX1133. This study demonstrated that MRTX1133 inhibited both the inactive and active state of KRASG12D and showed potent antitumor activity in several preclinical models of pancreatic and colorectal cancer, especially when combined with cetuximab, a monoclonal antibody against the EGFR, or BYL‐719, a potent PI3Kα inhibitor.

Source: Molecular Oncology

DOI: 10.1002/1878-0261.13341

Authors: Matthias Drosten, Mariano Barbacid

Institutions: Consejo Superior de Investigaciones Científicas, Universidad de Salamanca, Centro de Investigación del Cáncer, Instituto de Biología Molecular y Celular del Cáncer de Salamanca, Spanish National Cancer Research Centre

Language: English

Topic: Protein Kinase Regulation and GTPase Signaling

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,800