L1790

L-685,458

>96% (HPLC), solid

• Synonym(s): (5S)-(t-Butoxycarbonylamino)-6-phenyl-(4R)hydroxy-(2R)benzylhexanoyl)-L-leu-L-phe-amide
• Empirical Formula (Hill Notation): C₃₉H₅₂O₆N₄
• CAS Number: 292632-98-5
• Molecular Weight: 672.85
• MDL number: MFCD03093402
• UNSPSC Code: 12352200
• PubChem Substance ID: 329817393
• NACRES: NA.77

Properties

• 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)

Description

Application

L-685,458 has been used to attenuate Notch signalling in ovary culture.[1] It has also been used to analyze the specificity of the γ-secretase activity in brain tissue samples.[2]

Biochem/physiol Actions

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

L-685,458 mimics the transition state in aspartyl protease. It possesses an IC50 of 17nM with respect to inhibition of Aβ synthesis.[3] 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).[4] L-685,458 targets the active site and substrate binding site of the enzyme.[5]

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.

Safety Information

• Storage Class: 11 - Combustible Solids
• wgk_germany: WGK 3
• flash_point_f: Not applicable
• flash_point_c: Not applicable
• ppe: Eyeshields, Gloves, type N95 (US)