RXFP1-Agonist-8
Band: www.medchemexpress.com
The first potent and selective small-molecule agonist of human relaxin receptor 1 (RXFP1)
A cell-permeable 2-acetamido-N-phenylbenzamide that selectively activates human, but not mouse, LGR7/RXFP1-mediated cAMP induction (EC50 = 200 nM in THP1) via allosteric interaction with the ECL3 region without competing against ECL2-mediated relaxin binding or affecting AVPR1B- or LGR8/RXFP2-mediated cAMP induction. Although shown to be ~150-fold and 500-fold less potent than relaxin (RLX), respectively, in VEGF mRNA induction and cellular impedance assays, pharmacokinetic studies reveal superior in vivo stability to RLX and in vivo bioavailability in mice via oral (Cmax/Tmax = 604 nM/plasma/1 h and 1026 ng/g heart/1.5 h; 30 mg/kg) or intraperitoneal (Cmax/Tmax = 9.29 µM/plasma/1 h and 28.6 µmol/kg heart/1 h; 30 mg/kg) administration with good aqueous solubility (7 µM in PBS).
Reference:
1) Xiao, J., et al. 2013. Nat. Commun. 4, 1953.