Belnacasan (VX-765)

ArtNr	S2228-50
Hersteller	Selleckchem
CAS-Nr.	273404-37-8
Menge	50 mg
Quantity options	10 mg 1 g 10 g 10 mM/1 mL 200 mg 50 mg 5 g
Kategorie	Inhibitors & Compound Libraries Small Molecules
Typ	Inhibitors
Specific against	other
Smiles	CCOC1C(CC(=O)O1)NC(=O)C2CCCN2C(=O)C(C(C)(C)C)NC(=O)C3=CC(=C(C=C3)N)Cl
ECLASS 10.1	32160490
ECLASS 11.0	32160490
UNSPSC	12000000
Alias	Caspase-1,Caspase
Lieferbar
Storage Conditions	2 years -80 in solvent
Molecular Weight	509
Administration	Administered via p.o.
Animal Models	Collagen-induced arthritis mouse model.
Clinical Trials	VX-765 is currently in Phase II clinical trials in patients with treatment-resistant partial epilepsy.
Dosages	<=200 mg/kg
Formulation	VX-765 is dissolved in 25% Cremophor EL.
IC50	0.8 nM (Ki) [1], 0.8 nM (Ki) [1], 0.8 nM (Ki) [1], 0.8 nM (Ki) [1], 0.8 nM (Ki) [1], 0.8 nM (Ki) [1]
In vitro	VX-765 is an orally absorbed prodrug of VRT-043198, which exhibits potent inhibition against ICE/caspase-1 and caspase-4 with Ki of 0.8 nM and less than 0.6 nM, respectively. And VRT-043198 also inhibits IL-1beta release from both PBMCs and whole blood with IC50 of 0.67 uM and 1.9 uM, respectively., [1]
In vivo	In collagen-induced arthritis mouse model, VX-765 (200 mg/kg) inhibits LPS-induced IL-1beta production by about 60%, and results in, a dose-dependent, statistically significant reduction in the inflammation scores and effective protection from joint changes., [1] In vivo, VX-765 blocks kindling epileptogenesis in rats by preventing IL-1beta increase in forebrain astrocytes without significant effect on afterdischarge duration., [2] In the mouse model of acute seizures, VX-765 (50 mg/kg-200 mg/kg) produces the anticonvulsant effect by delaying the time to onset of the first seizure and decreasing the number of seizures as well as their total duration by average 50% and 64%., [3] In adult rats with genetic absence epilepsy (GAERS), VX-765, after the 3rd drug injection, significantly reduces the cumulative duration and number of spike-and-wave discharges (SWDs) by 55% on average by selectively blocking IL-1beta biosynthesis., [4]
Kinase Assay	Protease Enzyme Assays, Enzyme inhibition is assayed by tracking of the rate of hydrolysis of an appropriate substrate labeled with either p-nitroaniline or aminomethyl coumarin (AMC) as follows: ICE/caspase-1, suc-YVAD-p-nitroanilide, caspase-4, Ac-WEHD-AMC, caspase-6, Ac-VEID-AMC, caspase-3, -7, -8, and -9, Ac-DEVD-AMC, and granzyme B, Ac-IEPD-AMC. Enzymes and substrates are incubated in a reaction buffer [10 mM Tris, pH 7.5, 0.1% (w/v) CHAPS, 1 mM dithiothreitol, and 5% (v/v) dimethyl sulfoxide] for 10 minutes at 37 C. Glycerol is added to the buffer at 8% (v/v) for caspase-3, -6, and -9 and granzyme B to improve stability of enzymes. The rate of substrate hydrolysis is monitored using a fluorometer.
Solubility (25C)	DMSO 102 mg/mL, Water <1 mg/mL, Ethanol 102 mg/mL
Information	Belnacasan (VX-765) is a potent and selective inhibitor of caspase-1 with Ki of 0.8 nM in a cell-free assay. Phase 2.
Chemical Name	(S)-1-((S)-2-(4-amino-3-chlorobenzamido)-3, 3-dimethylbutanoyl)-N-((2R, 3S)-2-ethoxy-5-oxo-tetrahydrofuran-3-yl)pyrrolidine-2-carboxamide
Features	VX-765 is a potent and selective inhibitor of interleukin-converting enzyme/caspase-1.

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