SML2183

LY2955303

≥98% (HPLC)

• Synonym(s): 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
• Empirical Formula (Hill Notation): C₃₆H₄₂N₄O₃
• CAS Number: 1433497-19-8
• Molecular Weight: 578.74
• UNSPSC Code: 12352200
• NACRES: NA.77
• MDL number: MFCD31561443
• Assay: ≥98% (HPLC)
• Form: powder

Properties

• assay: ≥98% (HPLC)
• form: powder
• color: white to beige
• solubility: DMSO: 2 mg/mL, clear
• storage temp.: 2-8°C
• SMILES string: CC(C)(C)C1=CC(C2=CC(C3=CC=C(C(O)=O)C=C3)=NN2C4=CC=C(C=C4)C(N5CCN(CC5)C)=O)=CC(C(C)(C)C)=C1
• InChI key: YVXYHNKIOFSFMZ-UHFFFAOYSA-N

Description

Biochem/physiol Actions

LY2955303 is a potent and selective RARγ antagonist (Ki = 1.09 nM/RARγ, >1.70 μM/RARα, >2.98 μM/RARβ) that effectively inhibits RARγ-, but not RARα- or RARβ-, dependent reporter activity upon 15 nM all-trans retinoic acid stimulation in respective HEK293 transfectants (KB = 7.11 nM/RARγ, 1.51 μM/RARβ, 4.44 μM/RARα; 10 nM ATRA for RARβ 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 RARα antagonism-associated adverse effects (no testicular degeneration up to 10 mg/kg) seen with BMS-189453 treatment or in RARα-knockout mice.

Potent and selective retinoic acid receptor gamma (RARγ) antagonist with oral availability and in vivo efficacy in a rat model of osteoarthritis-like joint pain.

Safety Information

• Storage Class: 11 - Combustible Solids
• wgk: WGK 3
• flash_point_f: Not applicable
• flash_point_c: Not applicable