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 (T1/2 = 8.56 and 7.48 h in plasma and heart post single 30 mg/kg i.p. dosage in mice) to RLX (initial T1/2<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 (Cmax/Tmax = 604 nM/1 h and 1026 ng/g/1.5 h in plasma and heart, respectively; 30 mg/kg) or intraperitoneal (Cmax/Tmax = 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).
Biochem/physiol Actions
Cell permeable: yes
Primary Target hRXFP1
Reversible: yes
Packaging
Packaged under inert gas
Warning
Toxicity: Standard Handling (A)
Reconstitution
Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.
Other Notes
Xiao, J., et al. 2013. Nat. Commun.4, 1953.
Legal Information
CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany
Storage Class
11 - Combustible Solids
wgk_germany
WGK 3
flash_point_f
Not applicable
flash_point_c
Not applicable
Certificates of Analysis (COA)
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