Synonyms: 4-[5-[3,5-bis(1,1-Dimethylethyl)phenyl]-1-[4-[(4-methyl-1-piperazinyl)carbonyl]phenyl]-1H-pyrazol-3-yl]-benzoic acid; LY 2955303
Molecular Formula: C36H42N4O3
Molecular Weight: 578.74
Linear Structural Formula: C36H42N4O3
MDL Number: MFCD31561443
Purity: >=98% (HPLC)
Storage: 2-8C
Biochem Physiol Actions: LY2955303 is a potent and selective RARgamma antagonist (Ki = 1.09 nM/RARgamma, >1.70 muM/RARalpha, >2.98 muM/RARbeta) that effectively inhibits RARgamma-, but not RARalpha- or RARbeta-, dependent reporter activity upon 15 nM all-trans retinoic acid stimulation in respective HEK293 transfectants (KB = 7.11 nM/RARgamma, 1.51 muM/RARbeta, 4.44 muM/RARalpha; 10 nM ATRA for RARbeta transfectant). LY2955303 exhibits therapeutic efficacy in a rat model of osteoarthritis-like joint pain (ED50 = 0.72 mg/kg; single p.o. dosage 9 days post OA pain induction by MIA intra-articular injection) with good pharmacokinetic properties, aqueous solubility (>1.0 mg/mL in simulated intestinal fluid), oral availability (F = 26%; 10 mg/kg p.o. over 2 mg/kg i.v.), and no RARalpha antagonism-associated adverse effects (no testicular degeneration up to 10 mg/kg) seen with BMS-189453 treatment or in RARalpha-knockout mice.