| Chemical Properties | Back Directory | [density ]
1.27±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [form ]
Solid | [pka]
13.44±0.40(Predicted) | [color ]
Off-white to light yellow |
| Hazard Information | Back Directory | [Uses]
RM-018 is a potent, functionally distinct tricomplex KRASG12C active-state inhibitor. RM-018 retains the ability to bind and inhibit KRASG12C/Y96D and could overcome resistance. RM-018 binds specifically to the GTP-bound, active [“RAS(ON)”] state of KRASG12C[1]. | [Biological Activity]
RM-018 is a potent, functionally distinct tricomplex KRASG12C active-state inhibitor. RM-018 retains the ability to bind and inhibit KRASG12C/Y96D and could overcome resistance. RM-018 binds specifically to the GTP-bound, active ["RAS(ON)"] state of KRASG12C[1].
RM-018 is a "tricomplex" KRAS inhibitor, which exploits a highly abundant chaperone protein, cyclophilin A, to bind and inhibit KRASG12C[1].RM-018 (0.01-1000 nM; 72 hours) has IC50s of 1.4-3.5 nM (KRASG12C) and 2.8-7.3 nM (KRASG12C/Y96D) in NCI-H358, MIA PaCa-2, Ba/F3, and MGH1138-1 cells[1].RM-018 (0-100 nM; 4 hours) inhibits the expression of KRAS, pERK, and pRSK protein[1]. | [IC 50]
KRAS (G12C); KRAS (G12C/Y96D) | [References]
[1]. Tanaka N, et.al. Clinical Acquired Resistance to KRASG12C Inhibition through a Novel KRAS Switch-II Pocket Mutation and Polyclonal Alterations Converging on RAS-MAPK Reactivation. Cancer Discov. 2021 Aug;11(8):1913-1922. |
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