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Is Amgen's AMG 510 effective against KRASG12C?

Amgen's novel small-molecule inhibitor AMG 510 has become the first drug to show activity in patients with KRASG12C -mutant solid tumors. In a phase I trial, AMG 510 elicited partial responses in half of patients with non–small cell lung cancer (NSCLC) and led to stable disease in patients with colorectal or appendix cancer.

What's new in AMG 510?

AMG 510 is the first drug to successfully target KRAS (pictured above), which has long been considered undruggable. Researchers enrolled 35 patients with KRASG12C -mutant solid tumors who had received at least two prior therapies in the trial: 14 patients with NSCLC, 19 with colorectal cancer, and two with appendix cancer.

Does AMG 510 bind to Kras in the P2 pocket?

The X-ray co-crystal structure of the covalent AMG 510–KRAS (G12C) complex (Fig. 1a and Extended Data Table 1) highlighted the binding of AMG 510 in the P2 pocket of KRAS.

What is sotorasib (AMG 510)?

After multiple trials of drug development, sotorasib, otherwise known as AMG 510 or LUMAKRAS, a novel KRASG12Cinhibitor, was conditionally approved by the Food and Drug Administration (FDA) on May 28th 2021 and has shown promising results in both preclinical and clinical trials.


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