In immune-competent mice, treatment with AMG 510 resulted in a pro-inflammatory tumour microenvironment and produced durable cures alone as well as in combination with immune-checkpoint inhibitors. Cured mice rejected the growth of isogenic KRASG12D tumours, which suggests adaptive immunity against shared antigens. Reference: Nature. 2019 Nov;575(7781):217-223. https://www.nature.com/articles/s41586-019-1694-1
ChEBI: Sotorasib is a pyridopyrimidine that is pyrido[2,3-d]pyrimidin-2(1H)-one substituted by 4-methyl-2-(propan-2-yl)pyridin-3-yl, (2S)-2-methyl-4-(prop-2-enoyl)piperazin-1-yl, fluoro and 2-fluoro-6-hydroxyphenyl groups at positions 1, 4, 6 and 7, respectively. It is approved for the treatment of patients with non-small cell lung cancer having KRAS(G12C) mutations. It has a role as an antineoplastic agent. It is a member of acrylamides, a N-acylpiperazine, a pyridopyrimidine, a member of monofluorobenzenes, a member of methylpyridines, a tertiary carboxamide, a tertiary amino compound and a member of phenols.
It was examined whether AMG510 has an antitumor effect on the CACO-2 (human colorectal cancer) cells into which the KRAS G12C (Kirsten rat sarcoma 2 viral oncogene homolog mutation) gene was introduced. The results showed that there was a clear concentration dependent RPR (relative proliferation ratio) decrease and that AMG 510 selectively inhibited KRAS G12C in colon cancer cells in vitro (Fig. 4A). Reference: Mol Clin Oncol. 2021 Jul;15(1):148.
