Meldonium vs SLU-PP-915

Metabolic

Metabolic

Research Only

Research Only

Meldonium competitively inhibits γ-butyrobetaine hydroxylase — the enzyme that makes L-carnitine — and the carnitine transporter OCTN2, lowering intracellular L-carnitine. Reduced carnitine suppresses long-chain fatty-acid β-oxidation and shifts energy metabolism toward glycolysis, an effect proposed to be anti-ischemic/cardioprotective (Dambrova et al., 2016).

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).

No FDA/EMA-validated dose

No human dose established

Oral