MRTX849-amide-C4-(o)-carborane 

MRTX849-amide-C4-(o)-carborane is a KRAS^G12C inhibitor with mutation selectivity for cells expressing KRAS^G12C. MRTX849-amide-C4-(o)-carborane shows low intrinsic cytotoxicity in cancer cells. MRTX849-amide-C4-(o)-carborane covalently binds to Cys12 of KRAS^G12C, recruits Hsp70, promotes ubiquitination, and induces proteasome-dependent degradation of the target protein. MRTX849-amide-C4-(o)-carborane inhibits the activity of the downstream ERK signaling pathway and induces apoptosis signaling in cancer cells. MRTX849-amide-C4-(o)-carborane is applicable for the research of KRAS^G12C-positive cancers^[1].

HY8 (up to 50 μM; 72 h) shows no cytotoxicity at concentrations up to 50 μM in NCI-H23, MIA Paca-2, and HCT116 cells after 72 h of treatment, with an IC₅₀ >50 μM in all lines^[1].
HY8 (50 μM; 8 h, following 2 h pre-incubation with 5 μM MRTX849) covalently binds to the same Cys12 site on KRAS^G12C as MRTX849 in NCI-H23 cells, as pre-treatment with MRTX849 blocks HY8-induced KRAS^G12C degradation^[1].
HY8 (50 μM; 8 h, co-incubated with MG132) induces degradation of KRAS^G12C in NCI-H23 cells that is dependent on the proteasome pathway, as co-treatment with MG132 abrogates degradation^[1].
HY8 (10-50 μM; 8 h) activates pro-apoptotic signaling in NCI-H23 cells in vitro in a dose-dependent manner after 8 h treatment with 10, 30, or 50 μM, as shown by cleavage of PARP and caspase 3, and reduced CDK4 and cyclin D1 levels^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

816.42

C₃₈H₅₁B₁₀ClFN₇O₃

ClC1=CC=CC2=C1C(N(C3)CCC(C3=NC(OC[C@@H]4N(C(CCCCC5678[BH]9%10%11[BH]%12%13([BH]%10%14%15[BH]8%11%16[BH]%17%15%18%19)[BH]%20%14%18[BH]%21%22%17[CH]5%16%19[BH]%216%23[BH]9%127[BH]%20%13%22%23)=O)CCC4)=N%24)=C%24N%25C[C@H](CC#N)N(C(C(F)=C)=O)CC%25)=CC=C2

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Shao Y, et al. Carborane Hydrophobic Tags Drive Selective Degradation of Endogenous KRASG12C via HSP70–Ubiquitin–Proteasome Pathway[J]. ACS Bio & Med Chem Au, 2026.