BMS-229724

• CAT Number: I004435
• CAS Number: 221914-85-8
• Molecular Formula: C27H25Cl2F3O5S
• Molecular Weight: 589.447
• Purity: ≥95%
• Synonyms: BMS-229724; BMS 229724; BMS229724; 42AD6D8ECA; SCHEMBL3304414; LS-46643; UNII-42AD6D8ECA.;2-Butanone, 4-(4-(2-((2-(bis(4-chlorophenyl)methoxy)ethyl)sulfonyl)ethoxy)phenyl)-1,1,1-trifluoro-
• Target: Cytosolic Phospholipase A2 Inhibitor
• Solubility: Soluble in DMSO, not in water
• Storage: 0 - 4 °C for short term or -20 °C for long term
• IUPAC Name: 4-[4-[2-[2-[bis(4-chlorophenyl)methoxy]ethylsulfonyl]ethoxy]phenyl]-1,1,1-trifluorobutan-2-one
• InChI: InChI=1S/C27H25Cl2F3O5S/c28-22-8-4-20(5-9-22)26(21-6-10-23(29)11-7-21)37-16-18-38(34,35)17-15-36-24-12-1-19(2-13-24)3-14-25(33)27(30,31)32/h1-2,4-13,26H,3,14-18H2
• InChIKey: IKQYQTPQMAIVQR-UHFFFAOYSA-N
• SMILES: C1=CC(=CC=C1CCC(=O)C(F)(F)F)OCCS(=O)(=O)CCOC(C2=CC=C(C=C2)Cl)C3=CC=C(C=C3)Cl

BMS-229724 is a tight-binding inhibitor of cytosolic phospholipase A2 that acts at the lipid/water interface and possesses anti-inflammatory activity in skin inflammation models.

Reference

1:J Pharmacol Exp Ther. 2001 Jul;298(1):376-85. BMS-229724 is a tight-binding inhibitor of cytosolic phospholipase A2 that acts at the lipid/water interface and possesses anti-inflammatory activity in skin inflammation models.Burke JR,Davern LB,Stanley PL,Gregor KR,Banville J,Remillard R,Russell JW,Brassil PJ,Witmer MR,Johnson G,Tredup JA,Tramposch KM, PMID: 11408565 Abstract: Cytosolic phospholipase A2 (cPLA2) catalyzes the selective release of arachidonic acid from the sn-2 position of phospholipids and is believed to play a key cellular role in the generation of arachidonic acid. BMS-229724 (4-[4-[2-[2-[bis(4-chlorophenyl)methoxy]ethyl-sulfonyl]ethoxy]phenyl]-1,1,1-trifluoro-2-butanone) was found to be a selective inhibitor of cPLA2 (IC50 = 2.8 microM) in that it did not inhibit secreted phospholipase A2 in vitro, nor phospholipase C and phospholipase D in cells. The compound was active in inhibiting arachidonate and eicosanoid production in U937 cells, neutrophils, platelets, monocytes, and mast cells. With a synthetic covesicle substrate system, the dose-dependent inhibition could be defined by kinetic equations describing competitive inhibition at the lipid/water interface. The apparent equilibrium dissociation constant for the inhibitor bound to the enzyme at the interface (K(I)*(app)) was determined to be 1. 10(-5) mol% versus an apparent dissociation constant for the arachidonate-containing phospholipid of 0.35 mol%. The unit of concentration in the interface is mole fraction (or mol%), which is related to the surface concentration of substrate, rather than bulk concentration that has units of molarity. Thus, BMS-229724 represents a novel inhibitor of cPLA2, which partitions into the phospholipid bilayer and competes with phospholipid substrate for the active site. This potent inhibition of the enzyme translated into anti-inflammatory activity when applied topically (5%, w/v) to a phorbol ester-induced chronic inflammation model in mouse ears, inhibiting edema and neutrophil infiltration, as well as prostaglandin and leukotriene levels in the skin. In hairless guinea pigs, BMS-229724 was active orally (10 mg/kg) in a UVB-induced skin erythema model in hairless guinea pigs.