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K-Ras(G12C) inhibitor 12

Cat. No. M20595
K-Ras(G12C) inhibitor 12 Structure
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Biological Activity

K-Ras(G12C) inhibitor 12 is an allosteric inhibitor of oncogenic K-Ras(G12C).

Chemical Information
Molecular Weight 449.67
Formula C15H17ClIN3O3
CAS Number 1469337-95-8
Solubility (25°C) DMSO 27 mg/mL
Storage Powder          -20°C   3 years ;  4°C   2 years
In solvent       -80°C   6 months ;  -20°C   1 month
Conversion of different model animals based on BSA (PMID: 27057123)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

References

[1] Paul D Adams, et al. Protein Pept Lett. Targeting K-Ras Mutations Show Promise Towards Ending Ras's "Undruggable" Era

[2] Kotaro Sakamoto, et al. Sci Rep. The K-Ras(G12D)-inhibitory peptide KS-58 suppresses growth of murine CT26 colorectal cancer cell-derived tumors

[3] Daniel R Gentile, et al. Cell Chem Biol. Ras Binder Induces a Modified Switch-II Pocket in GTP and GDP States

[4] John C Hunter, et al. Proc Natl Acad Sci U S A. In situ selectivity profiling and crystal structure of SML-8-73-1, an active site inhibitor of oncogenic K-Ras G12C

[5] Sang Min Lim, et al. Angew Chem Int Ed Engl. Therapeutic targeting of oncogenic K-Ras by a covalent catalytic site inhibitor

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