BMS-299897

• CAT Number: I003006
• CAS Number: 290315-45-6
• Molecular Formula: C₂₄H₂₁ClF₃NO₄S
• Molecular Weight: 511.94
• Purity: ≥95%
• Target: Gamma Secretase
• Solubility: DMSO: ≥ 30 mg/mL
• Storage: Store at -20°C
• IUPAC Name: 4-[2-[(1R)-1-(N-(4-chlorophenyl)sulfonyl-2,5-difluoroanilino)ethyl]-5-fluorophenyl]butanoic acid
• InChI: InChI=1S/C24H21ClF3NO4S/c1-15(21-11-7-18(26)13-16(21)3-2-4-24(30)31)29(23-14-19(27)8-12-22(23)28)34(32,33)20-9-5-17(25)6-10-20/h5-15H,2-4H2,1H3,(H,30,31)/t15-/m1/s1
• InChIKey: IZAOBRWCUGOKNH-OAHLLOKOSA-N
• SMILES: CC(C1=C(C=C(C=C1)F)CCCC(=O)O)N(C2=C(C=CC(=C2)F)F)S(=O)(=O)C3=CC=C(C=C3)Cl

BMS-299897 (Cat.No:I003006) is a sulphonamide γ-secretase inhibitor with an IC50 of 7nM for Aβ inhibition in HEK293 cells. In vitro studies show that BMS-299897 reduces the levels of Aβ peptides, and in vivo studies demonstrate dose and time-dependent reductions of amyloid-β-peptide in the brain, cerebrospinal fluid, and plasma of transgenic mice. BMS-299897 also attenuates Aβ25-35-induced Aβ1-42 seeding and toxicity and improves short and long-term memory abilities.

Reference

1:The γ-secretase inhibitor 2-[(1R)-1-[(4-chlorophenyl)sulfonyl](2,5-difluorophenyl) amino]ethyl-5-fluorobenzenebutanoic acid (BMS-299897) alleviates Aβ1-42 seeding and short-term memory deficits in the Aβ25-35 mouse model of Alzheimer/’s disease. Meunier J, Villard V, Givalois L, Maurice T.Eur J Pharmacol. 2013 Jan 5;698(1-3):193-9. doi: 10.1016/j.ejphar.2012.10.033. Epub 2012 Nov 2. PMID: 23123349 2:Studies on the pharmacokinetics and metabolism of a gamma-secretase inhibitor BMS-299897, and exploratory investigation of CYP enzyme induction. Zheng M, Wang J, Lubinski J, Flint OP, Krishna R, Yao M, Pursley JM, Thakur A, Boulton DW, Santone KS, Barten DM, Anderson JJ, Felsenstein KM, Hansel SB.Xenobiotica. 2009 Jul;39(7):544-55. doi: 10.1080/00498250902928555. PMID: 19480557 3:Liquid-liquid extraction of strongly protein bound BMS-299897 from human plasma and cerebrospinal fluid, followed by high-performance liquid chromatography/tandem mass spectrometry. Xue YJ, Pursley J, Arnold M.J Pharm Biomed Anal. 2007 Apr 11;43(5):1728-36. Epub 2007 Jan 3. PMID: 17204392 4:In vitro and in vivo metabolism of a gamma-secretase inhibitor BMS-299897 and generation of active metabolites in milligram quantities with a microbial bioreactor. Zhang D, Hanson R, Roongta V, Dischino DD, Gao Q, Sloan CP, Polson C, Keavy D, Zheng M, Mitroka J, Yeola S.Curr Drug Metab. 2006 Dec;7(8):883-96. PMID: 17168689 5:Reductions in beta-amyloid concentrations in vivo by the gamma-secretase inhibitors BMS-289948 and BMS-299897. Anderson JJ, Holtz G, Baskin PP, Turner M, Rowe B, Wang B, Kounnas MZ, Lamb BT, Barten D, Felsenstein K, McDonald I, Srinivasan K, Munoz B, Wagner SL.Biochem Pharmacol. 2005 Feb 15;69(4):689-98. Epub 2005 Jan 7. PMID: 15670587