Roxadustat vs SLU-PP-915

Metabolic

Metabolic

Research Only

Research Only

Roxadustat inhibits HIF prolyl-hydroxylase (a 2-oxoglutarate analog), preventing HIF-α degradation. Stabilized HIF (predominantly HIF-2α) induces endogenous erythropoietin transcription and improves iron mobilization (hepcidin suppression), stimulating erythropoiesis — mimicking a hypoxic response without exogenous EPO (EMA product information).

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 performance dose established

No human dose established

Oral

Oral (research only)