Table 2.
A Brief Summary of Current K-RasG12C Inhibitors
| K-RasG12C Inhibitor | Developer/Year | IC50 for H358 Cells In Vitro | Cmax at 100 mg/kg p.o. | Significance | Stage | Recommended Phase 2 Dose | Overall Response Rate | Reference |
|---|---|---|---|---|---|---|---|---|
| Compound 12 | University of California, San Francisco (2013) | 10 μM | NA | first proof-of-concept K-RasG12C inhibitor | NA | NA | NA | Ostrem et al.3 |
| ARS-853 | Wellspring Biosciences (2016) | 2.5 μM | NA | robust cell-active K-RasG12C inhibitor | NA | NA | NA | Patricelli et al.4 |
| ARS-1620 | Wellspring Biosciences (2018) | 120 nM | 1.3 μM | first proof-of-concept compound for in vivo K-RasG12C inhibition | preclinical | NA | NA | Janes et al.5 |
| AMG-510 | Amgen Inc (2019) | 10 nM | 1.2 μM | first potent and selective K-RasG12C inhibitor in clinic, first proof-of-concept compound for K-RasG12C inhibition-driven antitumor immunity | phase 1/2 | 960 mg, daily | 48% in KRASG12C NSCLC, 6% in other KRASG12C mutant cancers | Canon et al.6 |
| MRTX1257 | Mirati Therapeutics, Inc (2019) | NA | NA | highly sensitive K-RasG12C inhibitor | preclinical | NA | NA | Marx et al.52 |
| MRTX849 | Mirati Therapeutics, Inc (2019) | 100 nM | 1.4 μM | potent and highly selective K-RasG12C inhibitor in clinic | phase 1/2 | 600 mg twice daily | 50% in KRASG12C NSCLC, 14% in other KRASG12C mutant cancers | Hallin et al.7 |
| JNJ-74699157 (ARS-3248) | Johnson & Johnson/Wellspring Biosciences (2019) | NA | NA | potent and highly selective clinical K-RasG12C inhibitor | phase 1 | NA | NA | NCT04006301 at ClinicalTrials.gov |
| LY3499446 | Eli Lilly | NA | NA | potent and highly selective clinical K-RasG12C inhibitor | phase 1/2 | NA | NA | NCT04165031 at ClinicalTrials.gov |