Camonsertib-RP-3500-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemECamonsertibCat.No.:HY-139609CASNo.:2417489-10-0Synonyms:RP-3500;ATRinhibitor4分⼦式:C₂₁H₂₆N₆O₃分⼦量:410.47作⽤靶点:ATM/ATR;mTOR作⽤通路:CellCycle/DNADamage;PI3K/Akt/mTOR储存⽅式:4°C,sealedstorage,awayfrommoistureandlight*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoistureandlight)溶解性数据体外实验DMSO:50mg/mL(121.81mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.4362mL12.1812mL24.3623mL5mM0.4872mL2.4362mL4.8725mL10mM0.2436mL1.2181mL2.4362mL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(sealedstorage,awayfrommoistureandlight)。-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%salineSolubility:≥1.25mg/mL(3.05mM);Clearsolution1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥1.25mg/mL(3.05mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥1.25mg/mL(3.05mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Camonsertib(RP-3500)⼀种⼝服有效的，选择性ATR激酶抑制剂(ATRi)，在⽣化试验中的IC50为1.00nM。Camonsertib对ATR的选择性mTOR的30倍(IC50=120nM)，ATM、DNA-PK和PI3Kα激酶的>2,000倍。Camonsertib具有有效的抗肿瘤活性。IC50&TargetATRATMmTOR>30μM(IC50)120nM(IC50)体外研究Camonsertib(RP-3500;1μM;1-24hours)inhibitsCHK1(Ser345)phosphorylationfrom1to3hours[1].CamonsertibinhibitsGemcitabinestimulatedATRphosphorylationofitssubstratepCHK1(Ser345)withanIC50of0.33nMinaLoVocell-basedassay[1].WesternBlotAnalysis[1]CellLine:LoVoandCW-2humancoloncancercelllinesConcentration:1μMIncubationTime:1,2,4,6,8,16,24hoursResult:InhibitedCHK1(Ser345)phosphorylationfrom1to3hours.Startingat4hours,CHK1(Ser345)becamere-phosphorylatedasDNA-PKcsbecameactivatedintreatedcells,alongwithitssubstratesKAP1andH2AX.体内研究Camonsertib(RP-3500;3,7,15mg/kg;Orally;oncedailyfor18days)producesdose-dependenttumorgrowthinhibitionwithaminimumeffectivedose(MED)of7mg/kginLoVoxenografts[1].Camonsertib(5,10mg/kg;Orally;oncedaily)producesstatisticallysignificanttumorgrowthinhibitionintheCW-2colonxenograftmodel[1].Camonsertib(7mg/kg;for7days)resultsin8.1-and2.7-foldinductionsofKAP1andDNA-PKcsphosphorylationinmicebearingLoVotumors[1].Camonsertibhasamoreprofoundanti-tumoreffectoccurredathigherdosesonthe3dayson/4daysoff(30mg/kg)and5dayson/2daysoff(25mg/kg)schedulescomparedwithconsecutivedailyadministrations(10mg/kg)atalowerdosefor14days[1].Camonsertib(15mg/kg)combinedPARPiOlaparib(80mg/kg;bothagentsdays1-3on/4daysoff)orsequential(PARPifor3daysfollowedbyRP-3500for3daysthen1dayoff)schedulesproducesgreaterantiTumoreffectscomparedwithsequentialadministrationwithoutaffectingtolerability[1].2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEAnimalModel:Femalemice(6-8weeksold)bearingLoVoxenografts[1]Dosage:3,7,15mg/kg(0.5%methylcellulose/0.02%SDSvehicle)Administration:Orally;oncedailyfor18daysResult:Produceddose-dependenttumorgrowthinhibitionwithaminimumeffectivedose(MED)of7mg/kg.Themaximumtolerateddose(MTD)was10mg/kgoncedailyonacontinuousdosingschedule.REFERENCES[1].AnneRoulston,etal.RP-3500:ANovel,PotentandSelectiveATRInhibitorthatisEffectiveinPreclinicalModelsasaMonotherapyandinCombinationwithPARPInhibitors.MolCancerTherMcePdfHeightCaution