NCATS-SM0225 is an endoplasmic reticulum-associated degradation ( ERAD ) inhibitor and a direct binder of VDAC1 , VDAC2 and VDAC3 . NCATS-SM0225 exhibits an IC 50 of 1.02 μM for ERAD and a K d of 3.13 μM for human VDAC1 binding. NCATS-SM0225 disrupts cellular calcium homeostasis, enhances VDAC1-IP3R coupling and activating PERK . NCATS-SM0225 selectively kills cancer cells, exhibits tumor growth inhibitory effects in melanoma xenograft models. NCATS-SM0225 can be used for research on multiple cancers including melanoma, as well as the molecular mechanisms of ERAD and calcium homeostasis regulation.
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