Antibodies
VX-765
- 貨號 Cat. No.
- S2228
- 規格 Size
- 10mgã€50mg
- 品牌 Brand
- Selleckchem
Description
VX-765
Catalog No.S2228
VX-765 is a potent and selective inhibitor of caspase-1 with Ki of 0.8 nM.
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Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw
Biological Activity
| Description | VX-765 is a potent and selective inhibitor of caspase-1 with Ki of 0.8 nM. | |||||
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| Targets | Caspase-1 | |||||
| IC50 | 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-1β release from both PBMCs and whole blood with IC50 of 0.67 μM and 1.9 μM, respectively. [1] | |||||
| In vivo | In collagen-induced arthritis mouse model, VX-765 (200 mg/kg) inhibits LPS-induced IL-1β 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-1β 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-1β biosynthesis. [4] | |||||
| Features | A potent and selective inhibitor of interleukin-converting enzyme/caspase-1. | |||||
Protocol(Only for Reference)
Kinase Assay: [1]
| 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 |
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Animal Study: [1]
| Animal Models | Collagen-induced arthritis mouse model. |
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| Dosages | ≤200 mg/kg |
| Administration | Administered via p.o. |
1
References
Clinical Trial Information( data from http://clinicaltrials.gov)
| NCT Number | Recruitment | Conditions | Sponsor /Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT00205465 | Completed | Psoriasis | Vertex Pharmaceuticals Incorporated | 2004-12 | Phase 2 |
| NCT01048255 | Completed | Partial Epilepsy | Vertex Pharmaceuticals Incorporated | 2010-01 | Phase 2 |
| NCT01501383 | Terminated | Epilepsy | Vertex Pharmaceuticals Incorporated | 2011-12 | Phase 2 |
Chemical Information
Download VX-765 SDFDownload VX-765 SDF
| Molecular Weight (MW) | 509 |
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| Formula | C24H33ClN4O6 |
| CAS No. | 273404-37-8, 851091-96-8 |
| Storage | 3 years -20℃Powder |
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| 6 months-80℃in DMSO | |
| Syonnyms | N/A |
| Solubility (25°C) * | In vitro | DMSO | 100 mg/mL (196 mM) |
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| Water | <1 mg/mL (<1 mM) | ||
| Ethanol | 100 mg/mL (196 mM) | ||
| * <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. | |||
| 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 |
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