MARY1 is a selective 5-HT2BR antagonist with an IC50 of 380 nM and a Ki of 764 nM [human 5-HT2BR]. It promotes mitochondrial biogenesis (MB) in the kidneys and enhances mitochondrial function by increasing mitochondrial respiration capacity, protein levels, and number in renal proximal tubular cells (RPTC). MARY1 induces MB in RPTCs through the 5-HT2BR and dual PI3K/AKT and RAS/MEK/ERK signaling pathways. It is useful for studying kidney diseases related to metabolic and mitochondrial dysfunction.

5-HT2B Receptor:380 nM

MARY1 exhibits moderate affinity for the 5-HT2BR receptor and does not significantly bind to the 5-HT2A/2C receptors. MARY1 (1 nM-1 μM, 24 hours) enhances maximal mitochondrial respiration in RPTCs and, specifically at 1 nM for 24 hours, it boosts this respiration, upregulates key mitochondrial bioenergetic genes, and increases mitochondrial quantity in RPTCs. Additionally, MARY1 elevates PGC-1α expression in scRNA-treated RPTCs, but not in siRNA-treated ones. At a concentration of 1 nM over 20 minutes, MARY1 induces MB in RPTCs through dual 5-HT2BR and PI3K/AKT signaling pathways, as well as the RAS/MEK/ERK pathway.

MARY1, administered as a single intraperitoneal injection at a dose of 0.3 mg/kg, induces MB in the renal cortex of male C57BL/6NCrl mice. Similarly, a single dose ranging from 0.15 to 0.3 mg/kg induces MB in the renal cortex of male SD rats. Moreover, a daily dose ranging from 0.15 to 15 mg/kg for four weeks does not cause mortality or abnormalities in organ or body weight in male SD rats.