CVM-1125

CVM-1125 is the **major active metabolite** of CVM-1118 (foslinanib), a small molecule anti-cancer agent in clinical development. CVM-1125 exerts **potent anti-tumor effects** in vitro across diverse cancer cell lines, inhibiting cell proliferation, inducing apoptosis, causing cell cycle arrest (at G2/M), and suppressing vasculogenic mimicry (VM) formation. Its mechanism involves direct binding to **TNF receptor associated protein 1 (TRAP1, also known as Hsp75)**, decreasing TRAP1 protein levels (via lysosomal degradation), and thereby interfering with mitochondrial signaling: inhibiting succinate dehydrogenase, lowering succinate accumulation, destabilizing hypoxia-inducible factor 1-alpha (HIF-1α), and promoting mitochondrial apoptosis. Notably, cell lines with loss-of-function mutations in STK11 or NF2 are more sensitive to CVM-1125, making these genetic alterations potential predictive biomarkers for responsiveness. CVM-1125 is rapidly formed in vivo after oral or intravenous administration of CVM-1118 and is likely the main bioactive anti-neoplastic species in this therapy.