DH20931 is a first-in-class, potent small-molecule agonist of Ceramide Synthase 2 (CerS2) with activation constant (Kact) of 16.54 nM, exhibits potent, broad-spectrum, and receptor-independent antitumor activity in vitro and in vivo.
DH20931 exhibits the significant growth inhibitory effects on both triple-positive and triple-negative human breast cancer cell lines with IC50 in the range of 0.3-3.9 uM.
DH20931 potently inhibits the viability of wild-type 4T1 cells, but CERS2-knockout cells.
DH20931 exerts its cytotoxic effects by directly activating CerS2 and driving the overproduction of pro-apoptotic VLCCs.
DH20931 inhibits breast cancer growth in vitro and in vivo, independent of hormone receptor status.
DH20931 induces ER stress through the ATF4 pathway in a CerS2-dependent manner.
DH20931 promotes a novel CerS2-IP3R1 interaction, enhances ER-mitochondria proximity, and triggers mitochondrial Ca²⁺ overload.
DH20931 induces robust apoptosis in breast cancer cells in a CerS2-dependent manner.