BAM15 vs SLU-PP-915

Metabolic

Metabolic

Research Only

Research Only

BAM15 increases proton permeability of the inner mitochondrial membrane, letting protons leak back into the matrix independent of ATP synthase — dissipating the proton-motive force and uncoupling electron transport from ATP synthesis, which raises substrate oxidation and heat production. Unlike DNP/FCCP it does not depolarize the plasma membrane at fully-uncoupling doses and is less cytotoxic than FCCP; downstream it activates AMPK (Kenwood et al., 2014). All data are cell/animal.

The estrogen-related receptors (ERRα/β/γ) are orphan nuclear receptors that act as master transcriptional regulators of oxidative metabolism, driving mitochondrial biogenesis, oxidative phosphorylation, fatty-acid oxidation, and the TCA cycle — largely as partners of the PGC-1 coactivators. SLU-PP-915 binds and activates all three ERR isoforms with an EC50 of roughly 400 nM at each. In its medicinal-chemistry design, the phenol and aniline groups of earlier ERR agonists were replaced with a boronic-acid moiety on a disubstituted thiophene scaffold, which preserved receptor activity while improving microsomal metabolic stability and oral exposure. In cells and in rodents it upregulates canonical ERR target genes including PGC-1α, lactate dehydrogenase A (LDHA), pyruvate dehydrogenase kinase 4 (PDK4), and DNA-damage-inducible transcript 4 (DDIT4).

Not established in humans; engineered for improved metabolic stability and oral exposure relative to first-generation ERR agonists