TMQ0153 (TMQ153) is a tetrahydrobenzimidazole derivative with cytotoxic potential against hematopoietic cancer cell lines, targets mitochondrial dynamics by inhibiting mitochondrial fusion protein optic atrophy 1 (OPA1), inducing metabolic reprogramming, and triggering apoptosis in AML cells.
TMQ0153 inhibits cell viability, proliferation and colony formation capacity of drug-sensitive and -resistant cancer cells.
TMQ0153 triggers a concentration-dependent induction of caspase-dependent and independent non-apoptotic cell death in K562 cells.
TMQ0153 activates necrostatin-1 sensitive necroptotic cell death.
TMQ0153 stimulates autophagy prior to necroptosis.
TMQ0153 depolarizes mitochondrial membrane potential and triggers necroptotic cell death through ROS formation.
TMQ0153 treatment significantly reduced OPA1 and mitofusin (MFN)2 protein levels and disrupted the mitochondrial morphology and function in AML cells.
TMQ0153 treatment reduces tumor volume and weight in MV4-11 xenografts in vivo.