5-Amino-1MQ vs SLU-PP-915

Metabolic

Metabolic

Research Only

Research Only

NNMT methylates nicotinamide using S-adenosylmethionine (SAM), producing 1-methylnicotinamide (MNA) and depleting both the NAD+ salvage precursor pool and the SAM methyl donor pool. By inhibiting NNMT, 5-Amino-1MQ lowers intracellular MNA and raises intracellular NAD+ and SAM. In adipocytes this has been reported to suppress lipogenesis and reduce adipocyte size in rodent models. Downstream links to SIRT1 activation and fat oxidation are frequently proposed but are not firmly established in vivo.

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; rodent PK supports once-daily dosing in research studies

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