Cellagen Technology LLC
 
작성일 : 16-02-15
[Cellagen Technology LLC] Disease Area, Neuroscience V
VX-765 l Caspase 1/Interleukin-converting enzyme inhibitor, YO-01027 (Dibenzazepine) l gamma-secretase inhibitor

 

Disease Area, Neuroscience V

 

 

Product Name: VX-765 l Caspase 1/Interleukin-converting enzyme inhibitor (#C8976-5)

 

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VX-765 is an orally-available prodrug of VRT-043198, an inhibitor of interleukin-converting enzyme /

caspase-1 subfamily caspases. VRT-043198 shows Ki values of 0.8 nM and 100-fold selectivity over other

non-ICE subfamily caspases. VRT-043198 showed no significant activity towards trypsin or cathepsin B. (1)

VRT-043198 inhibits IL-1b release from both PBMCs and whole blood with IC50 values of 0.67 and 1.9 uM,

respectively. Additionally in stimulated PBMCs, VRT-043198 dose-dependently inhibited IL-1b, IL-18, and

IFN-g, without affecting TNF-a release. In a hypoxia-induced apoptosis assay employing the NT2 human

neuroblastoma cell line, VRT-043198 did not alter ischemia-induced apoptosis up to concentrations of 100

uM. (1)

According to Vertex's news release , VX-765 has been shown to inhibit acute seizures in preclinical models

of acute epilepsy and has shown activity in preclinical models of chronic epilepsy that do not respond to

standard anti-epileptic drugs. (2)

 

Details

Chemical Formula:

 

C24H33CIN4O6

CAS No.:

 

273404-37-8

Molecular weight:

 

509

Purity:

> 98%

Appearance:

 

White

Chemical name:

 

 

(S)-1-((S)-2-(4-amino-3-chlorobenzamido)-3,3-dimethylbutanoyl)-N-((2R,3S)-2-

ethoxy-5-oxotetrahydrofuran-3-yl)pyrrolidine-2-carboxamide

Solubility:

 

Up to 50 mM in DMSO

Synonyms:

 

VX-765, VX765

Storage:

 

For longer shelf life, store solid powder at 4oC desiccated, or DMSO solution

at -20oC

 

References

1. Wannamaker et al., (S)-1-((S)-2-{[1-(4-Amino-3-chloro-phenyl)-methanoyl]-amino}-3,3-dimethyl-

   butanoyl)-pyrrolidine-2-carboxylic acid ((2R,3S)-2-ethoxy-5-oxo-tetrahydro-furan-3-yl)-amide (VX-765),

   an Orally Available Selective Interleukin (IL)-Converting Enzyme/ Caspase-1 Inhibitor, Exhibits Potent Anti-

   Inflammatory Activities by Inhibiting the Release of IL-1b and IL-18. J. Pharmacol. Exp. Ther. 2007, 321(2),

   509-516. Pubmed ID: 17289835   

2. http://investors.vrtx.com/releasedetail.cfm?ReleaseID=555967

 

 

Product Name: YO-01027 (Dibenzazepine) l gamma-secretase inhibitor (#C9601-2s)

 

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YO-01027 (Dibenzazepine, DBZ) is a dipeptidic g-secretase inhibitor with IC50 of 2.6 and 2.9 nM for APPL

and Notch, respectively. YO-01027 targets the Presenilin fragment. Increasing concentrations of YO-01027

administered to APPl- or Notch-expressing cells leads to the progressive accumulation of APPL C-terminal

fragments and a decrease in NICD production in a dose-dependent manner. [1]

In an in vitro model of human corneal and conjunctival epithelial cell differentation, YO-01027 impaired MUC16

biosynthesis in a concentration-dependent manner. [2]

In oncology models, YO-01027 preferentially inhibited Notch and significantly decreased MCF7 tumors and

increased latency compared with control mice. [3]

 

Details

Chemical Formula:

 

C26H23F2N3O3

CAS No.:

 

209984-56-5

Molecular weight:

 

463.48

Purity:

> 98%

Appearance:

 

White

Chemical name:

 

 

7-(S)-[N'(3,5-difluorophenylacetyl)-L-alaninyl]amino-5-methyl-5,7-dihydro-6H-

dibenz[b,d]azepin-6-one

Solubility:

 

Up to 100mM in DMSO

Synonyms:

 

YO-01027, YO01027, Dibenzazepine, Deshydroxy LY 411575

Storage:

 

For longer shelf life, store solid powder at 4oC desiccated, or DMSO solution

at -20oC

 

References

1. Groth et al., Pharmacological Analysis of Drosophila melanogaster g-Secretase with Respect to Differential

   Proteolysis of Notch and APP. Mol. Pharmacol. 2010, 77(4), 567-574. Pubmed ID: 20064975   

2. Xiong et al., Notch Signaling Modulates MUC16 Biosynthesis in an In Vitro Model of Human Corneal and

   Conjunctival Epithelial Cell Differentiation. Invest. Ophthalmol. Vis. Sci. 2011, 52(8), 5641-5646. Pubmed

   ID: 21508102

3. Harrison et al., Regulation of Breast Cancer Stem Cell Activity by Signaling through the Notch4 Receptor.    Cancer Res., 2010, 70, 709-718. Pubmed ID: 20068161

 

 

 

Ordering informations

    

Catalog No.

Product Name

Size

C8976-5

VX-765 l Caspase 1/Interleukin-converting enzyme inhibitor

5 mg, 25 mg & 100 mg

C9601-2s

YO-01027 (Dibenzazepine) l gamma-secretase inhibitor

2 mg, 10 mg & 50 mg

 

 

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