MARY1 is potent, and selective 5-hydroxytryptamine 2B receptor (5-HT2BR) antagonist with Ki of 764 nM, induces mitochondrial biogenesis (MB) enhances mitochondrial function in the kidney.
MARY1 shows no significant binding to 5-HT2A/2C receptors.
MARY1 selectively antagonizes the 5-HT2BR (IC50 = 381 nM; Emax = 90%), with no activity against 5-HT2A or 5-HT2C receptors.
MARY1 (1 nM-1 uM) enhances cellular mitochondrial maximal respiration, upregulates key genes responsible for mitochondrial bioenergetics, and increases the mitochondrial number in RPTCs, indicating MB, in primary rabbit renal proximal tubule cells (RPTCs).
MARY1 induces MB through 5-HT2BR and dual PI3K/AKT and RAS/MEK/ERK cell signaling pathways in vitro.
MARY1 (0.3 mg/kg, i.p.) induces MB in the renal cortex in vivo, resulted in increased PGC-1α and sirtuin 1 (SIRT1) mRNA, and mtDNA content (DLOOP and mtND1) in the renal cortex of control mice.