RXFP1 Agonist

A cell-permeable 2-acetamido-N-phenylbenzamide that selectively activates human, but not mouse, LGR7/RXFP1 (EC₅₀ = 94 and 200 nM, respectively, in cAMP induction using HEK293-hRXFP1 transfectant and THP1) via allosteric interaction with the ECL3 (TM helix 5 to EC loop3; V646 to T660) region without competing against ECL2-mediated relaxin binding, while exhibiting cytotoxicity only at much higher concentrations (IC₅₀ in 72 h = 9.4 µM in HEK293-RXFP1 cultures) and displaying no activity toward AVPR1B- (Arginine vasopressin receptor 1B) 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 (275% of basal level in THP1 cells; 250 nM) and cellular impedance assays (in HEK293-RXFP1 cultures), pharmacokinetic studies reveal superior in vivo stability (T_1/2 = 8.56 and 7.48 h in plasma and heart post single 30 mg/kg i.p. dosage in mice) to RLX (initial T_1/2<10 min in human; i.v.) and, while RLX is not orally active, this chemical agonist is demonstrated to be bioavailable in mice via oral (C_max/T_max = 604 nM/1 h and 1026 ng/g/1.5 h in plasma and heart, respectively; 30 mg/kg) or intraperitoneal (C_max/T_max = 9.29 µM/1 h and 28.6 µmol/kg/1 h in plasma and heart, respectively; 30 mg/kg) administration in vivo with good aqueous solubility (7 µM in PBS).

Cell permeable: yes

Primary Target
hRXFP1

Reversible: yes

Packaged under inert gas

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

Xiao, J., et al. 2013. Nat. Commun.4, 1953.

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Toxicity: Standard Handling (A)