MedKoo Biosciences/Venetoclax (ABT199)/205807/5g

Synonym:ABT199;ABT-199;ABT199;GDC0199;GDC0199;GDC0199;RG7601;RG7601;RG7601.Venetoclax.

IUPAC/ChemicalName:4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}sulfonyl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide

InChiKey:LQBVNQSMGBZMKD-UHFFFAOYSA-N

InChiCode:InChI=1S/C45H50ClN7O7S/c1-45(2)15-11-33(39(26-45)31-3-5-34(46)6-4-31)29-51-17-19-52(20-18-51)35-7-9-38(42(24-35)60-36-23-32-12-16-47-43(32)49-28-36)44(54)50-61(57,58)37-8-10-40(41(25-37)53(55)56)48-27-30-13-21-59-22-14-30/h4-10,12,16,23-25,28,30,48H,11,13-15,17-22,26-27,29H2,1-2H3,(H,47,49)(H,50,54)

SMILESCode:O=C(NS(=O)(C1=CC=C(NCC2CCOCC2)C([N+]([O-])=O)=C1)=O)C3=CC=C(N4CCN(CC5=C(C6=CC=C(Cl)C=C6)CC(C)(C)CC5)CC4)C=C3OC7=CN=C(NC=C8)C8=C7

TechnicalData

AdditionalInformation

GDC-0199(RG7601)isanovelsmallmoleculeBcl-2selectiveinhibitordesignedtorestoreapoptosis,alsoknownasprogrammedcelldeath,byblockingthefunctionofapro-survivalBcl-2familyprotein.TheBcl-2familyproteins,whichareexpressedathighlevelsinmanytumors,playacentralroleinregulatingapoptosisand,consequently,arethoughttoimpacttumorformation,tumorgrowthandresistance.
 
 
 

References

1:SeymourJ.ABT-199forChronicLymphocyticLeukemia.ClinAdvHematolOncol.2014Oct;12(10):698-700.PubMedPMID:25658896.

2:ChoudharyGS,Al-HarbiS,MazumderS,HillBT,SmithMR,BodoJ,HsiED,AlmasanA.MCL-1andBCL-xL-dependentresistancetotheBCL-2inhibitorABT-199canbeovercomebypreventingPI3K/AKT/mTORactivationinlymphoidmalignancies.CellDeathDis.2015Jan15;6:e1593.doi:10.1038/cddis.2014.525.PubMedPMID:25590803.

3:CaoY,YangG,HunterZR,LiuX,XuL,ChenJ,TsakmaklisN,HatjiharissiE,KananS,DavidsMS,CastilloJJ,TreonSP.TheBCL2antagonistABT-199triggersapoptosis,andaugmentsibrutinibandidelalisibmediatedcytotoxicityinCXCR4(Wild-type)andCXCR4(WHIM)mutatedWaldenstrommacroglobulinaemiacells.BrJHaematol.2015Jan12.doi:10.1111/bjh.13278.[Epubaheadofprint]PubMedPMID:25582069.

4:Johnson-FarleyN,VelizJ,BhagavathiS,BertinoJR.ABT-199,aBH3mimeticthatspecificallytargetsBcl-2,enhancestheantitumoractivityofchemotherapy,bortezomibandJQ1in"doublehit"lymphomacells.LeukLymphoma.2015Jan28:1-7.[Epubaheadofprint]PubMedPMID:25373508.

5:KoTK,ChuahCT,HuangJW,NgKP,OngST.TheBCL2inhibitorABT-199significantlyenhancesimatinib-inducedcelldeathinchronicmyeloidleukemiaprogenitors.Oncotarget.2014Oct15;5(19):9033-8.PubMedPMID:25333252;PubMedCentralPMCID:PMC4253416.

6:PeirsS,MatthijssensF,GoossensS,VandeWalleI,RuggeroK,deBockCE,DegryseS,Canté-BarrettK,BriotD,ClappierE,LammensT,DeMoerlooseB,BenoitY,PoppeB,MeijerinkJP,CoolsJ,SoulierJ,RabbittsTH,TaghonT,SpelemanF,VanVlierbergheP.ABT-199mediatedinhibitionofBCL-2asanoveltherapeuticstrategyinT-cellacutelymphoblasticleukemia.Blood.2014Dec11;124(25):3738-47.doi:10.1182/blood-2014-05-574566.Epub2014Oct9.PubMedPMID:25301704.

7:ZhaoX,BodoJ,SunD,DurkinL,LinJ,SmithMR,HsiED.CombinationofibrutinibwithABT-199:synergisticeffectsonproliferationinhibitionandapoptosisinmantlecelllymphomacellsthroughperturbationofBTK,AKTandBCL2pathways.BrJHaematol.2015Mar;168(5):765-8.doi:10.1111/bjh.13149.Epub2014Oct4.PubMedPMID:25284608.

8:ABT-199showseffectivenessinCLL.CancerDiscov.2014Sep;4(9):OF7.doi:10.1158/2159-8290.CD-NB2014-102.Epub2014Jul3.PubMedPMID:25185206.

9:ChonghaileTN,RoderickJE,GlenfieldC,RyanJ,SallanSE,SilvermanLB,LohML,HungerSP,WoodB,DeAngeloDJ,StoneR,HarrisM,GutierrezA,KelliherMA,LetaiA.MaturationstageofT-cellacutelymphoblasticleukemiadeterminesBCL-2versusBCL-XLdependenceandsensitivitytoABT-199.CancerDiscov.2014Sep;4(9):1074-87.doi:10.1158/2159-8290.CD-14-0353.Epub2014Jul3.PubMedPMID:24994123;PubMedCentralPMCID:PMC4154982.

10:WeiA.ABT-199partnerswithazacitidinetocontestmyeloidmalignancies.LeukLymphoma.2015Jan;56(1):8-9.doi:10.3109/10428194.2014.919638.Epub2014Jul15.PubMedPMID:24794804.