MedKoo Biosciences/GSK2606414/406393/25mg

Synonym:GSK2606414;GSK-2606414;GSK2606414;GSKPERKInhibitor.

IUPAC/ChemicalName:1-(5-(4-amino-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)indolin-1-yl)-2-(3-(trifluoromethyl)phenyl)ethanone

InChiKey:SIXVRXARNAVBTC-UHFFFAOYSA-N

InChiCode:InChI=1S/C24H20F3N5O/c1-31-12-18(21-22(28)29-13-30-23(21)31)15-5-6-19-16(11-15)7-8-32(19)20(33)10-14-3-2-4-17(9-14)24(25,26)27/h2-6,9,11-13H,7-8,10H2,1H3,(H2,28,29,30)

SMILESCode:FC(C1=CC(CC(N2CCC3=C2C=CC(C4=CN(C)C5=NC=NC(N)=C54)=C3)=O)=CC=C1)(F)F

TechnicalData

AdditionalInformation

   
ThechemicalstructuresofGSK2606414 andGSK2656157areverysimilar.Thefollowinggraphicisaside-by-sidecomparison.
  

References

1:Rojas-RiveraD,DelvaeyeT,RoelandtR,NerinckxW,AugustynsK,VandenabeeleP,BertrandMJM.WhenPERKinhibitorsturnouttobenewpotentRIPK1inhibitors:criticalissuesonthespecificityanduseofGSK2606414andGSK2656157.CellDeathDiffer.2017Apr28.doi:10.1038/cdd.2017.58.[Epubaheadofprint]PubMedPMID:28452996.

2:WenL,XiaoB,ShiY,HanF.PERKsignallingpathwaymediatessingleprolongedstress-induceddysfunctionofmedialprefrontalcortexneurons.Apoptosis.2017Jun;22(6):753-768.doi:10.1007/s10495-017-1371-5.PubMedPMID:28391375.

3:JiangX,WeiY,ZhangT,ZhangZ,QiuS,ZhouX,ZhangS.EffectsofGSK2606414oncellproliferationandendoplasmicreticulumstressassociatedgeneexpressioninretinalpigmentepithelialcells.MolMedRep.2017May;15(5):3105-3110.doi:10.3892/mmr.2017.6418.Epub2017Mar30.PubMedPMID:28358434.

4:ZhangJ,FengZ,WangC,ZhouH,LiuW,KanchanaK,DaiX,ZouP,GuJ,CaiL,LiangG.CurcuminderivativeWZ35efficientlysuppressescoloncancerprogressionthroughinducingROSproductionandERstress-dependentapoptosis.AmJCancerRes.2017Feb1;7(2):275-288.eCollection2017.PubMedPMID:28337376;PubMedCentralPMCID:PMC5336501.

5:SharmaR,QuiltyF,GilmerJF,LongA,ByrneAM.Unconjugatedsecondarybileacidsactivatetheunfoldedproteinresponseandinducegolgifragmentationviaasrc-kinase-dependantmechanism.Oncotarget.2017Jan3;8(1):967-978.doi:10.18632/oncotarget.13514.PubMedPMID:27888615;PubMedCentralPMCID:PMC5352210.

6:AbhishekK,SardarAH,DasS,KumarA,GhoshAK,SinghR,SainiS,MandalA,VermaS,KumarA,PurkaitB,DikhitMR,DasP.PhosphorylationofTranslationInitiationFactor2-AlphainLeishmaniadonovaniunderStressIsNecessaryforParasiteSurvival.MolCellBiol.2016Dec19;37(1).pii:e00344-16.Print2017Jan1.PubMedPMID:27736773;PubMedCentralPMCID:PMC5192082.

7:WuWS,ChienCC,ChenYC,ChiuWT.ProteinKinaseRNA-LikeEndoplasmicReticulumKinase-MediatedBcl-2ProteinPhosphorylationContributestoEvodiamine-InducedApoptosisofHumanRenalCellCarcinomaCells.PLoSOne.2016Aug2;11(8):e0160484.doi:10.1371/journal.pone.0160484.eCollection2016.PubMedPMID:27483435;PubMedCentralPMCID:PMC4970736.

8:CelardoI,CostaAC,LehmannS,JonesC,WoodN,MencacciNE,MallucciGR,LohSH,MartinsLM.Mitofusin-mediatedERstresstriggersneurodegenerationinpink1/parkinmodelsofParkinson'sdisease.CellDeathDis.2016Jun23;7(6):e2271.doi:10.1038/cddis.2016.173.PubMedPMID:27336715;PubMedCentralPMCID:PMC5143399.

9:GuthrieLN,ABIramanK,PlylerES,SprenkleNT,GibsonSA,McFarlandBC,RajbhandariR,RowseAL,BenveNISTeEN,MearesGP.AttenuationofPKR-likeERKinase(PERK)SignalingSelectivelyControlsEndoplasmicReticulumStress-inducedInflammationWithoutCompromisingImmunologicalResponses.JBiolChem.2016Jul22;291(30):15830-40.doi:10.1074/jbc.M116.738021.Epub2016May23.PubMedPMID:27226638;PubMedCentralPMCID:PMC4957064.

10:ZhouY,QiB,GuY,XuF,DuH,LiX,FangW.PorcineCircovirus2DeploysPERKPathwayandGRP78forItsEnhancedReplicationinPK-15Cells.Viruses.2016Feb20;8(2).pii:E56.doi:10.3390/v8020056.PubMedPMID:26907328;PubMedCentralPMCID:PMC4776210.

11:ChenTC,ChienCC,WuMS,ChenYC.EvodiaminefromEvodiarutaecarpainducesapoptosisviaactivationofJNKandPERKinhumanovariancancercells.Phytomedicine.2016Jan15;23(1):68-78.doi:10.1016/j.phymed.2015.12.003.Epub2015Dec22.PubMedPMID:26902409.

12:YanF,CaoS,LiJ,DixonB,YuX,ChenJ,GuC,LinW,ChenG.PharmacologicalInhibitionofPERKAttenuatesEarlyBrainInjuryAfterSubarachnoidHemorrhageinRatsThroughtheActivationofAkt.MolNeurobiol.2017Apr;54(3):1808-1817.doi:10.1007/s12035-016-9790-9.Epub2016Feb18.PubMedPMID:26887383.

13:RadfordH,MorenoJA,VerityN,HallidayM,MallucciGR.PERKinhibitionpreventstau-mediatedneurodegenerationinamousemodeloffrontotemporaldementia.ActaNeuropathol.2015Nov;130(5):633-42.doi:10.1007/s00401-015-1487-z.Epub2015Oct8.PubMedPMID:26450683;PubMedCentralPMCID:PMC4612323.

14:JohariYB,EstesSD,AlvesCS,SinacoreMS,JamesDC.Integratedcellandprocessengineeringforimprovedtransientproductionofa"difficult-to-express"fusionproteinbyCHOcells.BiotechnolBioeng.2015Dec;112(12):2527-42.doi:10.1002/bit.25687.Epub2015Sep7.PubMedPMID:26126657.

15:JamisonS,LinY,LinW.PancreaticendoplasmicreticulumkinaseactivationpromotesmedulloblastomacellmigrationandinvasionthroughinductionofvascularendothelialgrowthfactorA.PLoSOne.2015Mar20;10(3):e0120252.doi:10.1371/journal.pone.0120252.eCollection2015.PubMedPMID:25794107;PubMedCentralPMCID:PMC4368580.

16:HallidayM,RadfordH,SekineY,MorenoJ,VerityN,leQuesneJ,OrtoriCA,BarrettDA,FromontC,FischerPM,HardingHP,RonD,MallucciGR.PartialrestorationofproteinsynthesisratesbythesmallmoleculeISRIBpreventsneurodegenerationwithoutpancreatictoxicity.CellDeathDis.2015Mar5;6:e1672.doi:10.1038/cddis.2015.49.PubMedPMID:25741597;PubMedCentralPMCID:PMC4385927.

17:MoonHS,KimB,GwakH,SuhDH,SongYS.AutophagyandproteinkinaseRNA-likeendoplasmicreticulumkinase(PERK)/eukaryoticinitiationfactor2alphakinase(eIF2α)pathwayprotectovariancancercellsfrommetformin-inducedapoptosis.MolCarcinog.2016Apr;55(4):346-56.doi:10.1002/mc.22284.Epub2015Feb7.PubMedPMID:25663310.

18:LinLC,SibilleE.Somatostatin,neuronalvulnerabilityandbehavioralemotionality.MolPsychiatry.2015Mar;20(3):377-87.doi:10.1038/mp.2014.184.Epub2015Jan20.PubMedPMID:25600109;PubMedCentralPMCID:PMC4355106.

19:Ounallah-SaadH,SharmaV,EdryE,RosenblumK.GeneticorpharmacologicalreductionofPERKenhancescortical-dependenttastelearning.JNeurosci.2014Oct29;34(44):14624-32.doi:10.1523/JNEUROSCI.2117-14.2014.PubMedPMID:25355215.

20:AxtenJM,RomerilSP,ShuA,RalphJ,MedinaJR,FengY,LiWH,GrantSW,HeerdingDA,MinthornE,MenckenT,GaulN,GoetzA,StanleyT,HassellAM,GampeRT,AtkinsC,KumarR.DiscoveryofGSK2656157:AnOptimizedPERKInhibitorSelectedforPreclinicalDevelopment.ACSMedChemLett.2013Aug12;4(10):964-8.doi:10.1021/ml400228e.eCollection2013Oct10.PubMedPMID:24900593;PubMedCentralPMCID:PMC4027568.