Ready for phase II!
After excellent results in animal trials and promising safety and efficacy results in Phase 1 clinical trials, the drug developed by the pharmaceutical company Amgen and currently referred to as AMG 510 is the first of the KRAS mutant protein inhibitors approved for clinical trials.
Incorrect operation of the KRAS gene, which encodes an important signaling protein, is one of the most common causes of malignant tumors. The specific mutant protein targeted by AMG 510 is called KRAS G12C and is present in approximately 13% of lung adenocarcinomas, 3% of rectal cancers, and 2% of other solid tumors.
Despite its significant role in the pathogenesis of cancer, scientists have not been able to develop KRAS-specific therapeutic agents for a long time because of the shape of this protein - it has an exceptionally smooth surface with no visible areas for binding the drug molecule. Developing a direct inhibitor, researchers from Amgen used X-ray crystallography of the KRAS G12C protein at the Berkeley Laboratory in San Francisco. High-resolution structural maps obtained using this method helped Amgen to make a breakthrough in opening a small niche on a mutant protein molecule. In subsequent studies, X-ray synchrotron radiation allowed scientists to investigate molecular interactions at the atomic level between KRAS G12C and potential inhibitory compounds that bind in the detected niche on the surface of the protein. The AMG 510 was the most promising candidate.
In preclinical trials in mice, treatment with AMG 510 led to regression of tumors associated with the KRAS G12C protein and increased the antitumor efficacy of chemotherapy. In immunocompetent mice, AMG 510 treatment resulted in the formation of a pro-inflammatory microenvironment in the tumor, demonstrating efficacy both as monotherapy and in combination with immune control inhibitors. In clinical trials, AMG 510 has demonstrated itself potentially as a disease-transforming therapy in patients for whom there are no effective treatment methods. Now he is admitted to the next stage of research.
The authors admit that it is very rare when a compound goes all the way to the very end from development to transformation into a medicine. That is why it is especially pleasant that the drug for the treatment of severe and common oncological diseases will soon be tested in phase 2 clinical trials.
Article by J.Canon et al. The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity is published in the journal Nature.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru Based on Berkeley Lab Materials: Unique Cancer Drug Discovered With Help From Advanced Light Source Begins Historical Clinical Trial.