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KRAS inhibitors: going noncovalent
KRAS (G12D) is the most frequent KRAS mutation in human cancer with particularly high frequencies in pancreatic and colorectal cancer. Informed by the structure of the KRAS(G12C) inhibitor adagrasib, Hallin et al. have now, through multiple rounds of structure‐based drug design, identified and valid...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9718111/ https://www.ncbi.nlm.nih.gov/pubmed/36383067 http://dx.doi.org/10.1002/1878-0261.13341 |
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author | Drosten, Matthias Barbacid, Mariano |
author_facet | Drosten, Matthias Barbacid, Mariano |
author_sort | Drosten, Matthias |
collection | PubMed |
description | KRAS (G12D) is the most frequent KRAS mutation in human cancer with particularly high frequencies in pancreatic and colorectal cancer. Informed by the structure of the KRAS(G12C) inhibitor adagrasib, Hallin et al. have now, through multiple rounds of structure‐based drug design, identified and validated a potent, selective, and noncovalent KRAS(G12D) inhibitor, MRTX1133. This study demonstrated that MRTX1133 inhibited both the inactive and active state of KRAS(G12D) 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. |
format | Online Article Text |
id | pubmed-9718111 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-97181112022-12-05 KRAS inhibitors: going noncovalent Drosten, Matthias Barbacid, Mariano Mol Oncol Commentary KRAS (G12D) is the most frequent KRAS mutation in human cancer with particularly high frequencies in pancreatic and colorectal cancer. Informed by the structure of the KRAS(G12C) inhibitor adagrasib, Hallin et al. have now, through multiple rounds of structure‐based drug design, identified and validated a potent, selective, and noncovalent KRAS(G12D) inhibitor, MRTX1133. This study demonstrated that MRTX1133 inhibited both the inactive and active state of KRAS(G12D) 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. John Wiley and Sons Inc. 2022-11-27 2022-12 /pmc/articles/PMC9718111/ /pubmed/36383067 http://dx.doi.org/10.1002/1878-0261.13341 Text en © 2022 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Commentary Drosten, Matthias Barbacid, Mariano KRAS inhibitors: going noncovalent |
title |
KRAS inhibitors: going noncovalent |
title_full |
KRAS inhibitors: going noncovalent |
title_fullStr |
KRAS inhibitors: going noncovalent |
title_full_unstemmed |
KRAS inhibitors: going noncovalent |
title_short |
KRAS inhibitors: going noncovalent |
title_sort | kras inhibitors: going noncovalent |
topic | Commentary |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9718111/ https://www.ncbi.nlm.nih.gov/pubmed/36383067 http://dx.doi.org/10.1002/1878-0261.13341 |
work_keys_str_mv | AT drostenmatthias krasinhibitorsgoingnoncovalent AT barbacidmariano krasinhibitorsgoingnoncovalent |