PF-3084014

PF-3084014 is a gamma-secretase inhibitor (IC50s = 6.2 and 1.2 nM in an enzyme assay and in whole cells, respectively). It inhibits gamma-secretase activity without inducing Notch-related toxicity (EC50s = 1,300-3,000 nM for B cells in fetal thymic organ cultures). It reduces the level of amyloid-beta (1-40) (Abeta40) fragments in mouse brain three hours following administration of 1 to 18 mg/kg doses and reduces Abeta42 fragment levels when administered at doses of 9 or 18 mg/kg. It also reduces Abeta fragments in guinea pig brain when administered at doses ranging from 0.3 to 3 mg/kg per day for five days.Formal Name: (2S)-2-[[(2S)-6,8-difluoro-1,2,3,4-tetrahydro-2-naphthalenyl]amino]-N-[1-[2-[(2,2-dimethylpropyl)amino]-1,1-dimethylethyl]-1H-imidazol-4-yl]-pentanamide. CAS Number: 1290543-63-3. Molecular Formula: C27H41F2N5O. Formula Weight: 489.6. Purity: >98%. Formulation: (Request formulation change), A solid. Solubility: DMSO: soluble. SMILES: FC1=CC(F)=C2C(CC[C@H](N[C@@H](CCC)C(NC3=CN(C(C)(C)CNCC(C)(C)C)C=N3)=O)C2)=C1. InChi Code: InChI=1S/C27H41F2N5O/c1-7-8-23(32-20-10-9-18-11-19(28)12-22(29)21(18)13-20)25(35)33-24-14-34(17-31-24)27(5,6)16-30-15-26(2,3)4/h11-12,14,17,20,23,30,32H,7-10,13,15-16H2,1-6H3,(H,33,35)/t20-,23-/m0/s1. InChi Key: VFCRKLWBYMDAED-REWPJTCUSA-N.