Table 1. kinact/Ki Relative to Active Concentration in Cellular Assays for Representative Covalent Inhibitors of KRasG12C and EGFR.
| Compound | Target | kinact/Ki [s–1 M–1] | Active concentration in cellular assays [nM] | Ref |
|---|---|---|---|---|
| Shokat Lead Cmpd 12 | KRasG12C | 0.33 | ≥10,000 | (23) |
| ARS-853 | KRasG12C | 250 | 2,500–10,000 | (23) |
| ARS-1620 | KRasG12C | 1,100 | 250–1,000 | (23) |
| MRTX849 (Adagrasib) | KRasG12C | 35,000 | 5–68 | (27) |
| AMG510 (Sotorasib) | KRasG12C | 9,900 | 5–14 | (28) |
| RMC6291 | KRasG12C | 289,000 | 50 | (29) |
| GDC-6036 | KRasG12C | 27,000 | 0.2 | (30) |
| JDQ443 | KRasG12C | 141,000 | 20 | (26) |
| BI-0474 | KRasG12C | 15,220 | 7–26 | (31) |
| Afatinib | wt EGFR | 6.3 | 11.5 | (22) |
| Afatinib | L858R/T790M EGFR | 15 | 7.3 | (22) |
| Osimertinib | wt EGFR | 28,000 | 480a | (33) |
| Osimertinib | L858R EGFR | 570,000 | 15–17a | (33) |
a
From ref (32).