MCB-294

MCB-294 inhibits the binding of SOS^cat to KRAS proteins and disrupted RAF-RBD peptide binding to active KRAS with IC₅₀ values approximately ranging from 1 to 70 nM and from 20 to 150 nM^[1].
MCB-294 (1 nM-100 μM, 5 days) shows significant anti-proliferative effects on KRAS-dependent cancer cells that rely on KRAS (as PC-1 (G12D), H358 (G12C), LS180 (G12V), HCT116 (G13D), etc.) for growth and survival (24 of 30 cell lines tested with a mean IC₅₀ of around 125 nM) while sparing normal cells (hTERT-HPNE, NCM460) (IC₅₀ > 10 μM)^[1].
MCB-294 (0-100 nM, 0-72 h) causes a dose-dependent reduction in p-ERK levels, persistently inhibits components of the MAPK signaling pathway (p-ERK, DUSP6, and cyclin D1) and induces apoptosis markers (CC3 and cPARP) in AsPC-1 and H358 tumors in all tested KRAS-dependent cancer cells including MIA PaCa-2 cells expressing KRAS^G12C, KRAS^G12C/Y96C, and KRAS^{G12C/H95D[1].
MCB-294 downregulates pro-survival genes (BIRC5, MCL1, and BCL2L1), upregulates pro-apoptotic genes (BBC3, BCL2L11, and BMF) and decreases KRAS-regulated genes such as CCND1, DUSP6, ETV4, SPRY2, and PHLDA1[1].
MCB-294 significantly upregulates the interferon-alpha response pathway in CD45+ immune cells isolated from CT26 tumors and increases the abundance of effector CD8+ T cells[1].}

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