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Small molecules irreversibly bind to a common oncogenic mutant, K-Ras(G12C). These compounds rely on the mutant cysteine for binding and therefore do not affect the wild-type protein. Crystallographic studies reveal the formation of a new pocket that is not apparent in previous structures of Ras, beneath the effector binding switch-II region. Binding of these inhibitors to K-Ras(G12C) disrupts both switch-I and switch-II, subverting the native nucleotide preference to favour GDP over GTP and impairing binding to Raf.
| Molecular Weight | 513.78 |
| Formula | C16H21ClIN3O4S |
| CAS Number | 1469337-91-4 |
| Solubility (25°C) | DMSO: ≥ 40 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Related Ras Products |
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| ZCL278
ZCL278 is a selective Cdc42 GTPase inhibitor with Kd of 11.4 μM. |
| Kobe0065
Kobe0065 is a novel and effective small-molecule compound inhibiting Ras–Raf interaction by SBDD, exhibits potent activity to competitively inhibit the binding of H-Ras·GTP to c-Raf-1 RBD with a Ki value of 46 ± 13 μM. |
| 6H05 trifluoroacetate
6H05 is a selective and allosteric inhibitor of oncogenic K-Ras(G12C). |
| CASIN
CASIN is a selective GTPase Cdc42 inhibitor with IC50 of 2 uM. |
| Salirasib
Salirasib is a potent competitive prenylated protein methyltransferase (PPMTase) inhibitor with Ki of 2.6 μM, which inhibits Ras methylation. Phase 2. |
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