MedKoo Biosciences/Niraparib HCl/201916/2g

RelatedCAS#:1038915-60-4(freebase) 1038915-64-8(HCl) 1038915-73-9(tosylate) 1613220-15-7(tosylatehydrate) 

Synonym:MK4827;MK4827;MK4827;Niraparib;NiraparibHCl;Niraparibhydrochloride.

IUPAC/ChemicalName:(S)-2-(4-(piperidin-3-yl)phenyl)-2H-indazole-7-carboxamidehydrochloride

InChiKey:YXYDNYFWAFBCAN-PFEQFJNWSA-N

InChiCode:InChI=1S/C19H20N4O.ClH/c20-19(24)17-5-1-3-15-12-23(22-18(15)17)16-8-6-13(7-9-16)14-4-2-10-21-11-14;/h1,3,5-9,12,14,21H,2,4,10-11H2,(H2,20,24);1H/t14-;/m1./s1

SMILESCode:O=C(C1=CC=CC2=CN(C3=CC=C([C@H]4CNCCC4)C=C3)N=C12)N.[H]Cl

TechnicalData

AdditionalInformation

RelatedCAS#
CAS#1038915-60-4(Niraparibfreebase);
CAS#1038915-64-8(NiraparibHClsalt);
CAS#1038915-73-9(Niraparibtosylate)

MK-4827displaysgoodpharmacokineticpropertiesandiscurrentlyinphaseIclin.trials.Thiscompd.displaysexcellentPARP1and2inhibitionwithIC50=3.8and2.1nM,resp.,andinawholecellassay,itinhibitedPARPactivitywithEC50=4nMandinhibitedproliferationofcancercellswithmutantBRCA-1andBRCA-2withCC50inthe10-100nMrange.MK-4827waswelltoleratedinvivoanddemonstratedefficacyasasingleagentinaxenograftmodelofBRCA-1deficientcancer. [See:JournalofMedicinalChemistry(2009),52(22),7170-7185.]
 
MK-4827wasfoundtobehighlyandsimilarlyeffectiveinbothradiationschedulesbutmaximumradiationenhancementwasobservedwhenMK-4827wasgivenatadoseof50 mg/kgoncedaily(EF = 2.2).MK-4827radiosensitizedallfourtumorsstudiedregardlessoftheirp53status.MK-4827reducedPARlevelsintumorsby1 hafteradministrationwhichpersistedforupto24 h.ThislongperiodofPARPinhibitionpotentiallyaddstotheflexibilityofdesignoffutureclinicaltrials.Thus,MK-4827showshighpotentialtoimprovetheefficacyofradiotherapy.(source:InvestNewDrugs.2011Nov30.[Epubaheadofprint])
 

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