L685458 | CAS#292632-98-5 | γ -secretase inhibitor

L685458
featured

WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 500910

CAS#: 292632-98-5

Description: L685458 is a potent and selective γ -secretase inhibitor (IC50 = 17 nM) that displays > 50-fold selectivity over a range of aspartyl, serine and cysteine proteases. L685458 also exhibits equal potency for inhibition of A β 40 and A β 42 peptides (IC50 values are 48 and 67 nM respectively in human neuroblastoma cells). Also regulates CXCR4 and VEGFR2 expression through inhibition of Notch signaling in vitro.

Chemical Structure

L685458

CAS# 292632-98-5

Product data Instruction

Theoretical Analysis

MedKoo Cat#: 500910
Name: L685458
CAS#: 292632-98-5
Chemical Formula: C39H52N4O6
Exact Mass: 672.39
Molecular Weight: 672.867
Elemental Analysis: C, 69.62; H, 7.79; N, 8.33; O, 14.27

Price and Availability

Size	Price	Availability
1mg	USD 250	2 Weeks
5mg	USD 650	2 Weeks
10mg	USD 950	2 Weeks
Bulk inquiry Welcome, Customer: Please do not inquire quote if your intended use is for a patient since our products are for research use and for chemical synthesis use, not for human use . For in-stock products, we listed price in the web page. You may inquire prices for which sizes were not listed. If no price is listed, this means the product is not in stock at the moment, which may be available via custom synthesis. For cost-effective reason, minimum order of 1g is requested (typically very expensive). The lead time is usually 2-4 months. Quote of less than 1g will not be provided. MedKoo may not offer quote for below reasons: (1) current available synthetic method appears to be extremely expensive which is obviously not affordable to most customers; (2) Key raw material to make the product is temporally not available; (3) DEA controlled substances; (4) the product is under patent protection in customer’s country.

Synonym: L685458; L-685458; L 685458; L685,458, L-685,458; L 685,458

IUPAC/Chemical Name: tert-butyl ((2S,3R,5R)-6-(((S)-1-(((S)-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.

InChi Key: MURCDOXDAHPNRQ-ZJKZPDEISA-N

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+,33+,34-/m1/s1

SMILES Code: O=C(OC(C)(C)C)N[C@H]([C@H](O)C[C@@H](CC1=CC=CC=C1)C(N[C@@H](CC(C)C)C(N[C@@H](CC2=CC=CC=C2)C(N)=O)=O)=O)CC3=CC=CC=C3

Appearance: Solid powder

Purity: >98%

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >5 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:

Product Data:

Product Data

Instruction:

View handling instruction

Biological target:	L-685458 is a potent transition state analog (TSA) γ-secretase inhibitor (GSI).
In vitro activity:	The gamma-secretase inhibitor L-685,458 significantly reconstituted CXCR4 mRNA in rhDLL4-stimulated endothelial cells. Reference: Cancer Res. 2008 Mar 15;68(6):1889-95. https://pubmed.ncbi.nlm.nih.gov/18339870/
In vivo activity:	TBD

Solubility Data

	Solvent	Max Conc. mg/mL	Max Conc. mM
Solubility
	DMF	25.0	37.15
	DMSO	55.9	83.00

Preparing Stock Solutions

The following data is based on the product molecular weight 672.87 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:	1. Williams CK, Segarra M, Sierra Mde L, Sainson RC, Tosato G, Harris AL. Regulation of CXCR4 by the Notch ligand delta-like 4 in endothelial cells. Cancer Res. 2008 Mar 15;68(6):1889-95. doi: 10.1158/0008-5472.CAN-07-2181. PMID: 18339870. 2. Yao J, Duan L, Fan M, Wu X. Gamma-secretase inhibitors exerts antitumor activity via down-regulation of Notch and Nuclear factor kappa B in human tongue carcinoma cells. Oral Dis. 2007 Nov;13(6):555-63. doi: 10.1111/j.1601-0825.2006.01334.x. PMID: 17944672.
In vitro protocol:	1. Williams CK, Segarra M, Sierra Mde L, Sainson RC, Tosato G, Harris AL. Regulation of CXCR4 by the Notch ligand delta-like 4 in endothelial cells. Cancer Res. 2008 Mar 15;68(6):1889-95. doi: 10.1158/0008-5472.CAN-07-2181. PMID: 18339870. 2. Yao J, Duan L, Fan M, Wu X. Gamma-secretase inhibitors exerts antitumor activity via down-regulation of Notch and Nuclear factor kappa B in human tongue carcinoma cells. Oral Dis. 2007 Nov;13(6):555-63. doi: 10.1111/j.1601-0825.2006.01334.x. PMID: 17944672.
In vivo protocol:	TBD

Molarity Calculator

Calculate the mass, volume, or concentration required for a solution.

Mass

Concentration

Volume

M. Wt* g/mol

*When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and SDS / CoA (available online).

Reconstitution Calculator

The reconstitution calculator allows you to quickly calculate the volume of a reagent to reconstitute your vial. Simply enter the mass of reagent and the target concentration and the calculator will determine the rest.

Volume (to add to vial)

Mass (in vial)

Desired Reconstitution Concentration

Dilution Calculator

Calculate the dilution required to prepare a stock solution.

Concentration 1

Volume 1

Concentration 2

Volume 2

1: Singh CR, Bakhru P, Khan A, Li QB, Jagannath C. Cutting edge: Nicastrin and related components of γ-secretase generate a peptide epitope facilitating immune recognition of intracellular mycobacteria, through MHC class II-dependent priming of T cells. J Immunol. 2011 Dec 1;187(11):5495-9. Epub 2011 Oct 28. PubMed PMID: 22039303; PubMed Central PMCID: PMC3221744.

2: Hiyama A, Skubutyte R, Markova D, Anderson DG, Yadla S, Sakai D, Mochida J, Albert TJ, Shapiro IM, Risbud MV. Hypoxia activates the notch signaling pathway in cells of the intervertebral disc: implications in degenerative disc disease. Arthritis Rheum. 2011 May;63(5):1355-64. doi: 10.1002/art.30246. PubMed PMID: 21305512.

3: Knappenberger KS, Tian G, Ye X, Sobotka-Briner C, Ghanekar SV, Greenberg BD, Scott CW. Mechanism of gamma-secretase cleavage activation: is gamma-secretase regulated through autoinhibition involving the presenilin-1 exon 9 loop? Biochemistry. 2004 May 25;43(20):6208-18. PubMed PMID: 15147205.

4: Tian G, Ghanekar SV, Aharony D, Shenvi AB, Jacobs RT, Liu X, Greenberg BD. The mechanism of gamma-secretase: multiple inhibitor binding sites for transition state analogs and small molecule inhibitors. J Biol Chem. 2003 Aug 1;278(31):28968-75. Epub 2003 Apr 28. PubMed PMID: 12719412.

5: Tian G, Sobotka-Briner CD, Zysk J, Liu X, Birr C, Sylvester MA, Edwards PD, Scott CD, Greenberg BD. Linear non-competitive inhibition of solubilized human gamma-secretase by pepstatin A methylester, L685458, sulfonamides, and benzodiazepines. J Biol Chem. 2002 Aug 30;277(35):31499-505. Epub 2002 Jun 18. PubMed PMID: 12072428.

Your view history

L685458 featured