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L1790

Sigma-Aldrich

L-685,458

>96% (HPLC), solid

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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

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)

Related Categories

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 Aβ1-42 and Aβ1-40 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.

WGK

WGK 3

Flash Point(F)

Not applicable

Flash Point(C)

Not applicable

Personal Protective Equipment

dust mask type N95 (US), Eyeshields, Gloves

Certificates of Analysis (COA)

Search for Certificates of Analysis (COA) by entering the products Lot/Batch Number. Lot and Batch Numbers can be found on a product’s label following the words ‘Lot’ or ‘Batch’.

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Regulation of primordial follicle recruitment by cross-talk between the Notch and phosphatase and tensin homologue (PTEN)/AKT pathways
Wang LQ, et al.
Reproductive Biology and Endocrinology, 28(6), 700-712 (2016)
C-terminal fragment of presenilin is the molecular target of a dipeptidic gamma-secretase-specific inhibitor DAPT (N-[N-(3, 5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester)
Morohashi Y, et al.
The Journal of biological chemistry, 281(21), 14670-14676 (2006)
Effects of Alzheimer's disease-associated risk loci on cerebrospinal fluid biomarkers and disease progression: a polygenic risk score approach
Martiskainen H, et al.
Journal of Alzheimer'S Disease, 43(2), 565-573 (2015)
M S Shearman et al.
Biochemistry, 39(30), 8698-8704 (2000-07-29)
Progressive cerebral amyloid beta-protein (A beta) deposition is believed to play a central role in the pathogenesis of Alzheimer's disease (AD). Elevated levels of A beta(42) peptide formation have been linked to early-onset familial AD-causing gene mutations in the amyloid
Neural computation, 396-396 (2007)
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