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MedKoo Biosciences/Sonidegib (LDE-225)/205510/200mg

Sonidegib,alsoknownas,erismodegib,LDE225,NVP-LDE225,isanorallybioavailablesmall-moleculeSmoothened(Smo)antagoNISTwithpotentialantineoplasticactivity.ErismodegibselectivelybindstotheHedgehog(Hh)-ligandcellsurfacereceptorSmo,whichmayresultinthesuppressionoftheHhsignalingpathwayand,so,theinhibitionoftumorcellsinwhichthispathwayisabnormallyactivated.ItwasapprovedbytheFDAfortreatingbasalcellcarcinomainJuly2015.

MedKooCat#:205510
Name:Sonidegib(LDE-225)
CAS#:956697-53-3(freebase).
ChemicalFormula:C26H26F3N3O3
ExactMass:485.19263
MolecularWeight:485.49815
ElementalAnalysis:C,64.32;H,5.40;F,11.74;N,8.66;O,9.89


Synonym:LDE225;LDE225;LDE-225;NVP-LDE225;NVP-LDE-225;NVPLDE225;Erismodegib;Sonidegib;Odomzo.

IUPAC/ChemicalName:N-(6-((2R,6S)-2,6-dimethylmorpholino)pyridin-3-yl)-2-methyl-4"-(trifluoromethoxy)-[1,1"-biphenyl]-3-carboxamide

InChiKey:VZZJRYRQSPEMTK-CALCHBBNSA-N

InChiCode:InChI=1S/C26H26F3N3O3/c1-16-14-32(15-17(2)34-16)24-12-9-20(13-30-24)31-25(33)23-6-4-5-22(18(23)3)19-7-10-21(11-8-19)35-26(27,28)29/h4-13,16-17H,14-15H2,1-3H3,(H,31,33)/t16-,17+

SMILESCode:O=C(C1=C(C)C(C2=CC=C(OC(F)(F)F)C=C2)=CC=C1)NC3=CC=C(N4C[C@@H](C)O[C@@H](C)C4)N=C3


TechnicalData

Appearance:
Solidpowder

Purity:
>98%(orrefertotheCertificateofAnalysis)

CertificateofAnalysis:
ViewCoA:currentbatch,Lot#CRB50824

QCData:
ViewQCdata:currentbatch,Lot#CRB50824

SafetyDataSheet(MSDS):
ViewMaterialSafetyDataSheet(MSDS)

ShippingCondition:
Shippedunderambienttemperatureasnon-hazardouschemical.ThisproductisstableenoughforafewweeksduringordinaryshippingandtimespentinCustoms.

StorageCondition:
Dry,darkandat0-4Cforshortterm(daystoweeks)or-20Cforlongterm(monthstoyears).

Solubility:
SolubleinDMSO,notinwater

ShelfLife:
>2yearsifstoredproperly

DrugFormulation:
ThisdrugmaybeformulatedinDMSO

StockSolutionStorage:
0-4Cforshortterm(daystoweeks),or-20Cforlongterm(months).

HarmonizedSystemCode:
293490


AdditionalInformation

RelatedCAS#
CAS#956697-53-3(Sonidegibfreebase).
CAS#1218778-77-8(Sonidegibphosphate)


References

1:TibesR.Sonidegibphosphate:newapprovalforbasalcellcarcinoma.DrugsToday(Barc).2016May;52(5):295-303.doi:10.1358/dot.2016.52.5.2470697.PubMedPMID:27376162.

2:ZhouJ,QuinlanM,GlennK,BossH,PicardF,CastroH,SellamiD.Effectofesomeprazole,aprotonpumpinhibitoronthepharmacokineticsofsonidegibinhealthyvolunteers.BrJClinPharmacol.2016Jun8.doi:10.1111/bcp.13038.[Epubaheadofprint]PubMedPMID:27277189.

3:ChenL,SilapuntS,MigdenMR.Sonidegibforthetreatmentofadvancedbasalcellcarcinoma:acomprehensivereviewofsonidegibandtheBOLTtrialwith12-monthupdate.FutureOncol.2016May18.[Epubaheadofprint]PubMedPMID:27189494.

4:KishT,CorryL.Sonidegib(Odomzo)fortheSystemicTreatmentofAdultsWithRecurrent,LocallyAdvancedBasalCellSkinCancer.PT.2016May;41(5):322-5.PubMedPMID:27162473;PubMedCentralPMCID:PMC4849341.

5:IrvineDA,ZhangB,KinstrieR,TarafdarA,MorrisonH,CampbellVL,MokaHA,HoY,NixonC,ManleyPW,WheadonH,GoodladJR,HolyoakeTL,BhatiaR,CoplandM.DeregulatedhedgehogpathwaysignalingisinhibitedbythesmoothenedantagonistLDE225(Sonidegib)inchronicphasechronicmyeloidleukaemia.SciRep.2016May9;6:25476.doi:10.1038/srep25476.PubMedPMID:27157927;PubMedCentralPMCID:PMC4860619.

6:ZhouJ,QuinlanM,HurhE,SellamiD.Exposure-responseAnalysisofSonidegib(LDE225),anOralInhibitoroftheHedgehogSignalingPathway,forEffectivenessandSafetyinPatientswithAdvancedSolidTumors.JClinPharmacol.2016Apr20.doi:10.1002/jcph.749.[Epubaheadofprint]PubMedPMID:27095306.

7:DummerR,GuminskiA,GutzmerR,DirixL,LewisKD,CombemaleP,HerdRM,KAATzM,LoquaiC,StratigosAJ,SchulzeHJ,PlummerR,GogovS,PallaudC,YiT,MoneM,ChangAL,CornélisF,KudchadkarR,TrefzerU,LearJT,SellamiD,MigdenMR.The12-monthanalysisfromBasalCellCarcinomaOutcomeswithLDE225Treatment(BOLT):AphaseII,randomized,double-blindstudyofsonidegibinpatientswithadvancedbasalcellcarcinoma.JAmAcadDermatol.2016Jul;75(1):113-125.e5.doi:10.1016/j.jaad.2016.02.1226.Epub2016Apr7.PubMedPMID:27067394.

8:Sonidegib(Odomzo)forbasalcellcarcinoma.MedLettDrugsTher.2016Feb29;58(1489):31-2.PubMedPMID:26938701.

9:GoelV,HurhE,SteinA,NedelmanJ,ZhouJ,ChiparusO,HuangPH,GogovS,SellamiD.Populationpharmacokineticsofsonidegib(LDE225),anoralinhibitorofhedgehogpathwaysignaling,inhealthysubjectsandinpatientswithadvancedsolidtumors.CancerChemotherPharmacol.2016Apr;77(4):745-55.doi:10.1007/s00280-016-2982-1.Epub2016Feb22.PubMedPMID:26898300.

10:BurnessCB,ScottLJ.Sonidegib:AReviewinLocallyAdvancedBasalCellCarcinoma.TargetOncol.2016Apr;11(2):239-46.doi:10.1007/s11523-016-0418-9.Review.PubMedPMID:26867946.

11:WahidM,JawedA,MandalRK,DarSA,KhanS,AkhterN,HaqueS.Vismodegib,itraconazoleandsonidegibashedgehogpathwayinhibitorsandtheirrelativecompetenciesinthetreatmentofbasalcellcarcinomas.CritRevOncolHematol.2016Feb;98:235-41.doi:10.1016/j.critrevonc.2015.11.006.Epub2015Nov21.Review.PubMedPMID:26614022.

12:DanialC,SarinKY,OroAE,ChangAL.AnInvestigator-InitiatedOpen-LabelTrialofSonidegibinAdvancedBasalCellCarcinomaPatientsResistanttoVismodegib.ClinCancerRes.2016Mar15;22(6):1325-9.doi:10.1158/1078-0432.CCR-15-1588.Epub2015Nov6.PubMedPMID:26546616;PubMedCentralPMCID:PMC4794361.

13:BurnessCB.Sonidegib:FirstGlobalApproval.Drugs.2015Sep;75(13):1559-66.doi:10.1007/s40265-015-0458-y.Review.PubMedPMID:26323341.

14:MigdenMR,GuminskiA,GutzmerR,DirixL,LewisKD,CombemaleP,HerdRM,KudchadkarR,TrefzerU,GogovS,PallaudC,YiT,MoneM,KaatzM,LoquaiC,StratigosAJ,SchulzeHJ,PlummerR,ChangAL,CornélisF,LearJT,SellamiD,DummerR.Treatmentwithtwodifferentdosesofsonidegibinpatientswithlocallyadvancedormetastaticbasalcellcarcinoma(BOLT):amulticentre,randomised,double-blindphase2trial.LancetOncol.2015Jun;16(6):716-28.doi:10.1016/S1470-2045(15)70100-2.Epub2015May14.PubMedPMID:25981810.

15:ZollingerM,Lozac'hF,HurhE,EmotteC,BaulyH,SwartP.Absorption,distribution,metabolism,andexcretion(ADME)of¹⁴C-sonidegib(LDE225)inhealthyvolunteers.CancerChemotherPharmacol.2014Jul;74(1):63-75.doi:10.1007/s00280-014-2468-y.Epub2014May10.PubMedPMID:24817600.

16:RodonJ,TawbiHA,ThomasAL,StollerRG,TurtschiCP,BaselgaJ,SarantopoulosJ,MahalingamD,ShouY,MolesMA,YangL,GranvilC,HurhE,RoseKL,AmakyeDD,DummerR,MitaAC.AphaseI,multicenter,open-label,first-in-human,dose-escalationstudyoftheoralsmoothenedinhibitorSonidegib(LDE225)inpatientswithadvancedsolidtumors.ClinCancerRes.2014Apr1;20(7):1900-9.doi:10.1158/1078-0432.CCR-13-1710.Epub2014Feb12.PubMedPMID:24523439.

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