Sotorasib is First KRAS Inhibitor Approved by FDA - NCI
Jun 25, 2021 · The CodeBreaK 100 trial, funded by Amgen and NCI, is testing sotorasib (previously called AMG510) as a treatment for people with solid tumors that have KRAS G12C. The mutation, a hallmark of damage from cigarette smoke, is most common in lung cancer.
The clinical KRAS (G12C) inhibitor AMG 510 drives anti-tumour ... - Nature
Oct 30, 2019 · The discovery of the interaction with the His95 groove of KRAS (G12C) enabled markedly increased potency and the identification of AMG 510, a first-in-class oral KRAS (G12C) inhibitor with ...
Discovery of a Covalent Inhibitor of KRASG12C (AMG 510) for the ...
Dec 10, 2019 · Early results from this study have confirmed AMG 510 to demonstrate excellent tolerability and promising antitumor activity when administered as a monotherapy to patients with advanced KRAS p.G12C mutant solid tumors. (35) Dose-expansion efforts are currently ongoing.
CodeBreak 100: Phase I study of AMG 510, a novel KRAS
May 25, 2020 · AMG 510 is a first-in-class small molecule that specifically and irreversibly inhibits KRAS G12C. Previously, AMG 510 showed preliminary antitumor activity and favorable tolerability in pts with KRAS p.G12C mutant NSCLC or CRC in the phase 1, first-in-human trial. Here, we report results in pts with other tumor types from the same trial.
Targeting PI3Kα overcomes resistance to KRas - Nature
Nov 21, 2022 · AMG510 (Sotorasib) is the first KRas G12C inhibitor approved by the Food and Drug Administration (FDA) for treatment of KRASG12C -mutated locally advanced or metastatic non-small cell lung...
KRAS G12C Inhibition with Sotorasib in Advanced Solid Tumors
Sep 20, 2020 · Sotorasib (AMG 510) is a small molecule that specifically and irreversibly inhibits KRAS G12C through a unique interaction with the P2 pocket (Fig. S1 in the Supplementary Appendix,...
The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour ... - PubMed
Our efforts have led to the discovery of AMG 510, which is, to our knowledge, the first KRAS (G12C) inhibitor in clinical development. In preclinical analyses, treatment with AMG 510 led to the regression of KRAS G12C tumours and improved the anti-tumour efficacy of chemotherapy and targeted agents. In immune-competent mice, treatment with AMG ...
Spotlight on Sotorasib (AMG 510) for - PubMed Central (PMC)
After multiple adjustments were made, the (R)-38 compound, which was renamed as AMG 510, was created. It successfully demonstrated good activity in cellular assays, dose proportional plasma exposure, moderate permeability, and excellent oral bioavailability, and ultimately was approved as sotorasib.
KRAS mutation: from undruggable to druggable in cancer
Nov 15, 2021 · AMG510 is the first small molecule inhibitor specifically targeting KRAS (G12C) to enter clinical trials (NCT03600883), which specifically and irreversibly bind to Cys12 in the inducible S-IIP...
The Discovery Of Amgen's Novel Investigational KRAS (G12C) …
Through extensive compound screening and structure-based design, AMG 510 emerged as the top investigational candidate from the optimization of a series of H95 groove-binding molecules.
- Some results have been removed