Fluzoparib-SHR3162-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEFluzoparibCat.No.:HY-114778CASNo.:1358715-18-0Synonyms:SHR3162;Fuzuloparib分⼦式:C₂₂H₁₆F₄N₆O₂分⼦量:472.4作⽤靶点:PARP作⽤通路:CellCycle/DNADamage;Epigenetics储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:50mg/mL(105.84mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.1169mL10.5843mL21.1685mL5mM0.4234mL2.1169mL4.2337mL10mM0.2117mL1.0584mL2.1169mL请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；⼀旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存⽅式和期限：-80°C,6months;-20°C,1month。-80°C储存时，请在6个⽉内使⽤，-20°C储存时，请在1个⽉内使⽤。体内实验请根据您的实验动物和给药⽅式选择适当的溶解⽅案。以下溶解⽅案都请先按照InVitro⽅式配制澄的储备液，再依次添加助溶剂：(为保证实验结果的可靠性，澄的储备液可以根据储存条件，适当保存；体内实验的⼯作液，建议您现⽤现配，当天使⽤；以下溶剂前显⽰的百分⽐指该溶剂在您配制终溶液中的体积占⽐；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的⽅式助溶)1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:≥2.5mg/mL(5.29mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.29mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Fluzoparib(SHR3162)⼀种有效的⼝服活性PARP1抑制剂(IC50=1.46±0.72nM)，具有优越的抗肿瘤活性。Fluzoparib选择性地抑制同重组修复(HR)缺陷细胞的增殖，并使HR缺陷细胞对细胞毒性药物敏感。Fluzoparib在体内具有良好的药代动⼒学特性，可⽤于癌症研究。IC50&TargetPARP-11.46±0.72nM(IC50)体外研究Fluzoparib(30μM;24hour)increasesthelevelsofγH2AXinaconcentration‐dependentmannerinbothBRCA2‐deficientV‐C8cellsandBRCA1‐deficientMDA‐MB‐436cells,butnotinBRCA‐proficientV‐C8#13‐5cells[1].Fluzoparib(10G2/McheckpointinMDA‐MB‐436cells[1].Fluzoparib(10μM;72hour)increasestheprocessingofcaspase‐3,‐8,and‐9concentration‐dependently,itinducesG2/MarrestandapoptosisinHR‐deficientMDA‐MB‐436cellscells[1].FluzoparibispreferentiallyefficaciousagainstHR‐deficientcells,suchasBRCA1‐deficient(UWB1.289),MDA‐μM;24hour)increaseslevelsofbothpCDK1andcyclinB,indicatingactivationoftheMB‐436,BRCA2‐deficient(V‐C8),BRCA1‐deficientBRCA2‐mutated(MX‐1)andBRCA1hypermethylatedCaution:Producthasnotbeenfullyvalidatedformedicalapplications.(OVCAR‐8)cellswithIC50valuesof0.51μM,1.57μM,0.053μM,1.57μM,and1.43μM,respectively.TheForresearchuseonly.IC50valuesforHR‐proficientcells(V‐C8#13‐5andUWB1.289BRCA1)areboth>10μM[1].Tel:400-820-3792ax-mail:tech@MedChemE体内研究Fluzoparib(oralgavage;0.3,1,or3mg/kg;singledose)exhibitsagoodpharmacokineticprofileinFemaleBalb/cAnudemice(5‐6weeksold)micebearingMDA‐MB‐436.Afterasingleoraldose,fluzoparibisrapidly

absorbedandrapidlyclearedfrombloodatalldoselevels;plasmaconcentrationsoffluzoparibquicklyreaches

maximumwithin2hours.Incontrast,concentrationsoffluzoparibintumorremainsathighlevelsevenat24hoursafter

dosing(57.9ng/g,39.3ng/g,and85.6ng/gfordosesof0.3,1,and3mg/kg,respectively)[1].Fluzoparib(oralgavage;

30mg/kg;21days)apparentlyinhibitsthegrowthoftumorwithaninhibitionrateof59%(day21)at30mg/kg,andit

doesnotcausesignificantlossofbodyweightinNudemicebearingMDA‐MB‐436(BRCA1‐deficient)model

[1].Fluzoparib(3mg/kg)combineswithCisplatin,Paclitaxel,orApatinib(oralgavage;BID;21days)causesgrowth

inhibitionwithratesof61.4%,55.3%,and72.8%,respectively.Fluzoparib,Cisplatin,andApatinibcombinationor

Fluzoparib,Paclitaxel,andApatinibcombinationcancausegrowthinhibitionwithratesof84.9%and75.6%(day21),

respectivelyinvivo.The2‐drugcombinationofFluzoparibwithcisplatinandThe3‐drugFluzoparib,Cisplatin,and

Apatinibcombinationleadtolossofbodyweight,whereasnoapparenttoxicitywasobservedinothercombinations[1].REFERENCES[1].LeiWang,etal.Pharmacologiccharacterizationoffluzoparib,anovelpoly(ADP-ribose)polymeraseinhibitorundergoingclinicaltrials.CancerSci.2019Mar;110(3):1064-1075.[2].HuipingLi,etal.PhaseIdos