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
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
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/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMF |
25.0 |
37.15 |
| DMSO |
55.9 |
83.00 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
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.
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.
