Table 1.
Summary of RAS inhibitors in this review.
| Drug | Target | Kd | Mechanism | State | Citation | |
|---|---|---|---|---|---|---|
| Sotorasib (AMG510) | G12C | – | Covalent | Switch-II | Inactive | (19) |
| Adagrasib (MRTX849) | G12C | – | Covalent | Switch-II | Inactive | (16) |
| MRTX-1133 | G12D | (0.2pM)OFF | Non-covalent | Switch-II | Active/Inactive | (20) |
| RM-018 | G12C, Y96D | NA | Covalent and steric blockade | Switch I and II | Active | (21) |
| RMC-6236 | Pan-RAS | NA | Non-Covalent Steric blockade | Switch I and II | Active | (22) |
| RMC-6291 | G12C | NA | Covalent and steric blockade | Switch I and II | Active | (23) |
| RMC-7977 | Pan-RAS | CypA (195nM) KRASWT (120nM) KRASG12V/C/D/R (40-270nM) NRASWT (98nM) HRASWT (90nM) |
Non-covalent and steric blockade | Switch-I and II | Active | (24) |
| RMC-9805 | G12D | NA | Covalent and blockade | Switch I and II | Active | (25) |
| BI-2852 | *Pan-RAS | KRASWT
(7.5µM)ON/(1.1µM)OFF KRASG12D (740nM)ON/(2.0µM)OFF HRASWT (570nM)ON/(2.5 µM)OFF NRASWT (1.37µM)ON/(8.3µM)OFF |
Non-covalent | Between switch I and II | Active and inactive | (26) |
| BI-2865 | Pan-KRAS | KRASWT (6.9nM) KRASG12C (4.5nM) KRASG12D (32nM) KRASG12V (26nM) KRASG13D (4.3nM) |
Non-covalent | Switch-II | Inactive | (27) |
| Malolactone G12Di | G12D | – | Covalent | Switch-II | Active and inactive | (28) |
*Presumably.
Active/Inactive (ON/OFF).NA, Not applicable.