L-685,458

L-685,458 is an inhibitor of gamma-secretase (IC50 = 17 nM). It is selective for gamma-secretase over HIV-1, cathepsin D, trypsin, HepC3 NS3, papain, and calpain I proteases (IC50s = >1,000 nM). L-685,458 inhibits production of amyloid-beta (1-40) (Abeta40, Cay-21617) and Abeta42 (Cay-20574) in Neuro2A cells transfected with human amyloid precursor protein (APP, IC50s = 402 and 775 nM, respectively). It is also an inhibitor of Notch signaling that blocks hypoxia-induced activity of the Notch-responsive reporters 12xCSL and CBF1 in isolated rat intervertebral disc cells.Formal Name: N-[(2R,4R,5S)-5-[[(1,1-dimethylethoxy)carbonyl]amino]-4-hydroxy-1-oxo-6-phenyl-2-(phenylmethyl)hexyl]-L-leucyl-L-phenylalaninamide. CAS Number: 292632-98-5. Synonyms: gamma-Secretase Inhibitor X. Molecular Formula: C39H52N4O6. Formula Weight: 672.9. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 25 mg/ml, DMSO: 30 mg/ml. SMILES: CC(OC(N[C@H]([C@@H](C[C@H](C(N[C@H](C(N[C@H](C(N)=O)CC1=CC=CC=C1)=O)CC(C)C)=O)CC2=CC=CC=C2)O)CC3=CC=CC=C3)=O)(C)C. InChi Code: InChI=1S/C39H52N4O6/c1-26(2)21-33(37(47)41-32(35(40)45)24-29-19-13-8-14-20-29)42-36(46)30(22-27-15-9-6-10-16-27)25-34(44)31(23-28-17-11-7-12-18-28)43-38(48)49-39(3,4)5/h6-20,26,30-34,44H,21-25H2,1-5H3,(H2,40,45)(H,41,47)(H,42,46)(H,43,48)/t30-,31+,32. InChi Key: MURCDOXDAHPNRQ-ZJKZPDEISA-N.