ProductDescription
VX-765isanorally-availableprodrugofVRT-043198,aninhibitorofinterleukin-convertingenzyme/caspase-1subfamilycaspases.VRT-043198showsKivaluesof0.8nMand100-foldselectivityoverothernon-ICEsubfamilycaspases.VRT-043198showednosignificantactivitytowardstrypsinorcathepsinB.(1)
VRT-043198inhibitsIL-1breleasefrombothPBMCsandwholebloodwithIC50valuesof0.67and1.9uM,respectively.AdditionallyinstimulatedPBMCs,VRT-043198dose-dependentlyinhibitedIL-1b,IL-18,andIFN-g,withoutaffectingTNF-arelease.Inahypoxia-inducedapoptosisassayemployingtheNT2humanneuroblastomacellline,VRT-043198didnotalterischemia-inducedapoptosisuptoconcentrationsof100uM.(1)
AccordingtoVertex"snewsrelease,VX-765hasbeenshowntoinhibitacuteseizuresinpreclinicalmodelsofacuteepilepsyandhasshownactivityinpreclinicalmodelsofchronicepilepsythatdonotrespondtostandardanti-epilepticdrugs.(2)
Technicalinformation:
ChemicalFormula: | C24H33ClN4O6 | |
CAS#: | 273404-37-8 | |
MolecularWeight: | 509 | |
Purity: | >98% | |
Appearance: | white | |
ChemicalName: | (S)-1-((S)-2-(4-amino-3-chlorobenzamido)-3,3-dimethylbutanoyl)-N-((2R,3S)-2-ethoxy-5-oxotetrahydrofuran-3-yl)pyrrolidine-2-carboxamide | |
Solubility: | Upto50mMinDMSO | |
Synonyms: | VX-765,VX765 |
ShippingCondition:Theproductisshippedinaglassvialatambienttemperature.
Storagecondition:Forlongershelflife,storesolidpowderat4oCdesiccated,orstoreDMSOsolutionat-20oC.
Reference:
1. | Wannamakeretal.,(S)-1-((S)-2-{[1-(4-Amino-3-chloro-phenyl)-methanoyl]-amino}-3,3-dimethyl-butanoyl)-pyrrolidine-2-carboxylicacid((2R,3S)-2-ethoxy-5-oxo-tetrahydro-furan-3-yl)-amide(VX-765),anOrallyAvailableSelectiveInterleukin(IL)-ConvertingEnzyme/Caspase-1Inhibitor,ExhibitsPotentAnti-InflammatoryActivitiesbyInhibitingtheReleaseofIL-1bandIL-18.J.Pharmacol.Exp.Ther.2007,321(2),509-516.PubmedID:17289835 |
2. | http://investors.vrtx.com/releasedetail.cfm?ReleaseID=555967 |
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