Avagacestat

gamma-Secretase is a protease complex that cleaves single-pass transmembrane proteins, such as Notch receptors and beta-amyloid precursor protein (APP), within the transmembrane domain. Avagacestat is a potent, orally bioavailable inhibitor of gamma-secretase that more potently inhibits the cleavage of APP to Abeta40 than signaling through Notch (IC50s = 0.30 and 58 nM, respectively). It shows good pharmacokinetics in rats, dogs, and humans and passes the blood-brain barrier, reducing plasma, brain, and cerebrospinal fluid Abeta40 levels. While suppressing the production of Abeta38, Abeta40, and Abeta42, gamma-secretase inhibitors, including avagacestat, increase the level of APP beta-C-terminal fragment, both in vitro and in vivo, altering cell function. Avagacestat may impact Notch signaling in vivo, although it is generally considered a "Notch-sparing" gamma-secretase inhibitor.Formal Name: (2R)-2-[[(4-chlorophenyl)sulfonyl][[2-fluoro-4-(1,2,4-oxadiazol-3-yl)phenyl]methyl]amino]-5,5,5-trifluoro-pentanamide. CAS Number: 1146699-66-2. Synonyms: BMS 708163. Molecular Formula: C20H17ClF4N4O4S. Formula Weight: 520.9. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 2 mg/ml, DMSO: 15 mg/ml, DMSO:PBS(pH 7.2) (1:2): 0.3 mg/ml, Ethanol: 5 mg/ml. lambdamax: 244 nm. SMILES: O=S(N([C@@H](C(N)=O)CCC(F)(F)F)CC1=CC=C(C2=NOC=N2)C=C1F)(C3=CC=C(Cl)C=C3)=O. InChi Code: InChI=1S/C20H17ClF4N4O4S/c21-14-3-5-15(6-4-14)34(31,32)29(17(18(26)30)7-8-20(23,24)25)10-13-2-1-12(9-16(13)22)19-27-11-33-28-19/h1-6,9,11,17H,7-8,10H2,(H2,26,30)/t17-/m1/s1. InChi Key: XEAOPVUAMONVLA-QGZVFWFLSA-N.