L-685,458 - CAS 292632-98-5
Catalog number:
292632-98-5
Category:
Inhibitor
Not Intended for Therapeutic Use. For research use only.
Molecular Formula:
C39H52N4O6
Molecular Weight:
672.85
COA:
Inquire
Targets:
γ-secretase
Description:
L-685,458, a transition state analogue inhibitor, as a selective and potent inhibitor of γ-secretase (IC50 = 17 nM) it shows > 50-fold selectivity over a variety of aspartyl proteases tested. It is also a potent inhibitor of Aβ40 and Aβ42 peptides (in human neuroblastoma cells: IC50= 48 and 67 nM respectively). in vitro: A Notch inhibitor that blocks Notch activation in the two cell lines in terms of reduced cytoplasmic distribution and almost diminished nuclear labelling of Hes1 proteins; A γ-secretase inhibitor.
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Brife Description:
A potent inhibitor of Aβ40 and Aβ42 peptides (in human neuroblastoma cells: IC50= 48 and 67 nM respectively); A potent and selective γ -secretase inhibitor (IC50 = 17 nM)
Appearance:
White solid
Synonyms:
tert-butyl N-[(2S,3R,5R)-6-[[(2S)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-benzyl-3-hydroxy-6-oxo-1-phenylhexan-2-yl]carbamate; 1-benzyl-4-(1-(1-carbamoyl-2-phenylethylcarbamoyl-3-methylbutylcarbamoyl)-2-hydroxy-5; -phenylpentyl)carbamic acid tert-butyl ester; GSI-X cpd; L 685,458; L 685458; L-685,458; L-685458; CHEMBL302004; 292632-98-5; CHEBI:74921; InSolution™ gamma-Secretase Inhibitor X; AC1NUIFT; SCHEMBL3197800; AOB5511; BDBM50100434; ZINC26179223; AKOS024457203; CS-5258; NCGC00165962-01; AK517927; HY-19369; (5S)-(t-Butoxycarbonylamino)-6-phenyl-(4R)hydroxy-(2R)benzylhexanoyl)-L-leu-L-phe-amide; [(2R,4R,5S)-2-Benzyl-5-(Boc-amino)-4-hydroxy-6-phenyl-hexanoyl]-Leu-Phe-NH2; L-Phenylalaninamide, N-(5-(((1,1-dimethylethoxy)carbonyl)amino)-4-hydroxy-1-oxo-6-phenyl-2-(phenylmethyl)hexyl)-L-leucyl-,; (2R-(2R*,4R*,5S*))-; N-[(2R,4R,5S)-5-[[(1,1-DImethylethoxy)carbonyl]amino]-4-hydroxy-1-oxo-6- phenyl-2-(phenylmethyl)hexyl]-L-leucyl-L-phenylalaninamide
Solubility:
Soluble to 15 mM in DMSO
Storage:
Store in a cool and dry place and at 0 - 4℃ for short term (days to weeks) or -32℃ for long term (months to years).
MSDS:
Inquire
InChIKey:
MURCDOXDAHPNRQ-ZJKZPDEISA-N
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
Canonical SMILES:
CC(C)CC(C(=O)NC(CC1=CC=CC=C1)C(=O)N)NC(=O)C(CC2=CC=CC=C2)CC(C(CC3=CC=CC=C3)NC(=O)OC(C)(C)C)O
Current Developer:
γ-secretase
1.Linear non-competitive inhibition of solubilized human gamma-secretase by pepstatin A methylester, L685458, sulfonamides, and benzodiazepines.
Tian G1, Sobotka-Briner CD, Zysk J, Liu X, Birr C, Sylvester MA, Edwards PD, Scott CD, Greenberg BD. J Biol Chem. 2002 Aug 30;277(35):31499-505. Epub 2002 Jun 18.
Cerebral deposition of amyloid beta-protein (A beta) is believed to play a key role in the pathogenesis of Alzheimer's disease. Because A beta is produced from the processing of amyloid beta-protein precursor (APP) by beta- and gamma-secretases, these enzymes are considered important therapeutic targets for identification of drugs to treat Alzheimer's disease. Unlike beta-secretase, which is a monomeric aspartyl protease, gamma-secretase activity resides as part of a membrane-bound, high molecular weight, macromolecular complex. Pepstatin and L685458 are among several structural classes of gamma-secretase inhibitors identified so far. These compounds possess a hydroxyethylene dipeptide isostere of aspartyl protease transition state analogs, suggesting gamma-secretase may be an aspartyl protease. However, the mechanism of inhibition of gamma-secretase by pepstatin and L685458 has not been elucidated. In this study, we report that pepstatin A methylester and L685458 unexpectedly displayed linear non-competitive inhibition of gamma-secretase.
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Chemical Structure

CAS 292632-98-5 L-685,458

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