MedKoo Biosciences/PLX4720/202272/25mg

Synonym:PLX4720;PLX4720;PLX-4720.

IUPAC/ChemicalName:N-(3-(5-chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluorophenyl)propane-1-sulfonamide

InChiKey:YZDJQTHVDDOVHR-UHFFFAOYSA-N

InChiCode:InChI=1S/C17H14ClF2N3O3S/c1-2-5-27(25,26)23-13-4-3-12(19)14(15(13)20)16(24)11-8-22-17-10(11)6-9(18)7-21-17/h4-4,6-8,23H,2,5H2,1H3,(H,21,22)

SMILESCode:CCCS(=O)(NC1=CC=C(F)C(C(C2=CNC3=NC=C(Cl)C=C32)=O)=C1F)=O

TechnicalData

AdditionalInformation

PLX4720,a7-azaindolederivativethatinhibitsB-Raf(V600E)withanIC(50)of13nM,definesaclassofkinaseinhibitorwithmarkedselectivityinbothbiochemicalandcellularassays.PLX4720preferentiallyinhibitstheactiveB-Raf(V600E)kinasecomparedwithabroadspectrumofotherkinases,andpotentcytotoxiceffectsarealsoexclusivetocellsbearingtheV600Eallele.Consistentwiththehighdegreeofselectivity,ERKphosphorylationispotentlyinhibitedbyPLX4720inB-Raf(V600E)-bearingtumorcelllinesbutnotincellslackingoncogenicB-Raf.Inmelanomamodels,PLX4720inducescellcyclearrestandapoptosisexclusivelyinB-Raf(V600E)-positivecells.InB-Raf(V600E)-dependenttumorxenograftmodels,orallydosedPLX4720causessignificanttumorgrowthdelays,includingtumorregressions,withoutevidenceoftoxicity.Theworkdescribedhererepresentstheentirediscoveryprocess,frominitialidentificationthroughstructuralandbiologicalstudiesinanimalmodelstoapromisingtherapeuticfortestingincancerpatientsbearingB-Raf(V600E)-driventumors.seehttp://www.ncbi.nlm.nih.gov/pubmed/18287029.
 
 

References

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