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CHD-1 is a a hypoxia-activated antitumor prodrug. CHD-1 impairs mitochondrial morphology and membrane potential in hypoxic tumor cells, further triggering excessive mitophagy and inducing apoptosis. CHD-1 inhibits the growth of hypoxic tumor cells in vitro and the growth of HeLa xenograft in vivo.
MTK458 (MTK-458) is a potent, selective and brain penetrant PINK1 activator, MTK-458 promotes the first step in mitophagy.
MTK458 selectively activates PINK1 by stimulating dimerization and stabilization of the PINK1/TOM complex.
MTK458 binds to PINK1 and stabilizes an active heterocomplex, thereby increasing mitophagy.
MTK458 reduces the PINK1 substrate pS65-Ubiquitin (pUb) in primary neurons and in vivo.
MTK458 drives clearance of pathologic α-synuclein in vitro and in vivo, decreases pS129 α-synuclein aggregates and normalized both brain and corresponding plasma pUb levels in both cellular and animal models of α-synuclein aggregation (PD-like pathology).
SHS206 (compound 6n) is an orally active mitochondrial uncoupler that reduces hepatic triglyceride levels. SHS206 exhibits in vivo efficacy in the GAN mouse model and shows inhibitory effects on metabolic dysfunction-associated steatohepatitis (MASH).
CHD-1 is a a hypoxia-activated antitumor prodrug. CHD-1 impairs mitochondrial morphology and membrane potential in hypoxic tumor cells, further triggering excessive mitophagy and inducing apoptosis. CHD-1 inhibits the growth of hypoxic tumor cells in vitro and the growth of HeLa xenograft in vivo.
Mono-Pt is the first platinum(II) complex that inhibits cancer cells through a non-DNA-binding mitophagy pathway. Mono-Pt promotes the occurrence of mitophagy in cancer cells via stimulating endoplasmic reticulum stress (ERS) and activating unfolded protein response (UPR).
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