L-685 458

Application

L-685,458 has been used to attenuate Notch signalling in ovary culture. It has also been used to analyze the specificity of the γ-secretase activity in brain tissue samples.

Biochem/physiol Actions

L-685,458 mimics the transition state in aspartyl protease. It possesses an IC50 of 17nM with respect to inhibition of Aβ synthesis. It is known to block Notch (neurogenic locus notch homolog protein) signaling, which in turn reduces ERK (extracellular signal regulated kinase) phosphorylation by EGF (epidermal growth factor). L-685,458 targets the active site and substrate binding site of the enzyme.

L-685,458 is a potent, selective, structurally novel γ-secretase inhibitor; equipotent inhibitor of both Aβ_1-42 and Aβ_1-40 production.

Features and Benefits

This compound was developed by Merck & Co., Inc., Kenilworth, NJ, U.S.. To browse the list of other pharma-developed compounds and Approved Drugs/Drug Candidates, click here.

Legal Information

Manufactured and sold under license from Merck & Co., Inc., Kenilworth, NJ, U.S.

Molecular Weight: 672.85. Empirical Formula: C₃₉H₅₂O₆N₄. Quality Level: 100. Assay: >. 96% (HPLC). form: solid. color: white. solubility: DMSO: >. 10 . mg/mL. originator: Merck &. Co., Inc., Kenilworth, NJ, U.S.. storage temp.: −. 20°C. SMILES string: O[C@@H]([C@H](CC1: CC: CC: C1)NC(OC(C)(C)C): O)C[C@@H](CC2: CC: CC: C2)C(N[C@@H](CC(C)C)C(N[C@@H](CC3: CC: CC: C3)C(N): O): O): O. 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+,33+,34-/m1/s1. InChI key: MURCDOXDAHPNRQ-ZJKZPDEISA-N. Gene Information: human ... APH1A(51107), APH1B(83464), NCSTN(23385), NOTCH1(4851), NOTCH2(4853), NOTCH3(4854), NOTCH4(4855), PSEN1(5663), PSEN2(5664), PSENEN(55851)
mouse ... Aph1a(226548), Aph1b(208117), Ncstn(59287), Notch1(18128), Notch2(18129), Notch3(18131), Notch4(18132), Psen1(19164), Psen2(19165), Psenen(66340)
rat ... Aph1a(365872), Aph1b(300802), Ncstn(289231), Notch1(25496), Notch2(29492), Notch3(56761), Notch4(406162), Psen1(29192), Psen2(81751), Psenen(292788). Storage Class Code: 11 - Combustible Solids. WGK: WGK 3. Flash Point(F): Not applicable. Flash Point(C): Not applicable. Personal Protective Equipment: Eyeshields, Gloves, type N95 (US).