CHF5074

CHF5074 is a modulator of gamma-secretase and a derivative of flurbiprofen (Cay-70250). It inhibits the secretion of amyloid beta (1-42) (Abeta42) in H4-APP695NL human neuroglioma cells that overexpress a mutated form of amyloid precursor protein (APP, IC50 = 41 µM) and selectively inhibits secretion of Abeta42 over Abeta40 with 79% and 14% inhibition, respectively, at 100 µM. It does not inhibit COX-1 or COX-2 when used at concentrations up to 100 and 500 µM, respectively, and does not induce Notch cleavage in HEK293 cells expressing the APP mutant APPswe at 5 µM. CHF5074 decreases plasma levels of Abeta42 in the Tg2576 transgenic mouse model of Alzheimer's disease when administered at a dose of 12.5 mg/kg per day for seven days and reduces the plaque area and number of plaques in the brain of hAPP mice when administered in the diet at 375 ppm for six months. It decreases the distance traveled, but not the escape latency, in the Morris water maze in hAPP mice compared to hAPP animals administered a vehicle control.Formal Name: 1-(3',4'-dichloro-2-fluoro[1,1'-biphenyl]-4-yl)-cyclopropanecarboxylic acid. CAS Number: 749269-83-8. Synonyms: CS 1103, CSP1103, Itanapraced. Molecular Formula: C16H11Cl2FO2. Formula Weight: 325.2. Purity: >95%. Formulation: (Request formulation change), A solid. Solubility: DMF: 33 mg/ml, DMSO: 20 mg/ml, Ethanol: 10 mg/ml. lambdamax: 256 nm. SMILES: O=C(O)C1(CC1)C2=CC(F)=C(C3=CC(Cl)=C(Cl)C=C3)C=C2. InChi Code: InChI=1S/C16H11Cl2FO2/c17-12-4-1-9(7-13(12)18)11-3-2-10(8-14(11)19)16(5-6-16)15(20)21/h1-4,7-8H,5-6H2,(H,20,21). InChi Key: LIYLTQQDABRNRX-UHFFFAOYSA-N.