Hotline:400-820-3792Inhibitors?Agonists?ScreeningLibrarieswww.MedChemERBN-2397Cat.No.:HY-136174CASNo.:2381037-82-5分?式:C??H??F?N?O?分?量:523.43作?靶點(diǎn):PARP作?通路:CellCycle/DNADamage;Epigenetics儲(chǔ)存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:250mg/mL(477.62mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM1.9105mL9.5524mL19.1048mL5mM0.3821mL1.9105mL3.8210mL10mM0.1910mL0.9552mL1.9105mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲(chǔ)備液，并請(qǐng)注意儲(chǔ)備液的保存?式和期限。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥?式選擇適當(dāng)?shù)娜芙?案，配制前請(qǐng)先配制澄的儲(chǔ)備液，再依次添加助溶劑(為保證實(shí)驗(yàn)結(jié)果的可靠性，體內(nèi)實(shí)驗(yàn)的?作液，建議您現(xiàn)?現(xiàn)配，當(dāng)天使?；澄的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；以下溶劑前的百分?指該溶劑在您配制終溶液中的體積占?)：1.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥4.17mg/mL(7.97mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥4.17mg/mL(7.97mM);ClearsolutionBIOLOGICALACTIVITY1/3MasterofSmallMolecules—您?邊的抑制劑?師www.MedChemE?物活性RBN-2397?種強(qiáng)效的，跨物種的，且具有?服活性的NAD+競(jìng)爭(zhēng)性PARP7抑制劑，IC50值?于3nM。RBN-2397有選擇性地結(jié)合PARP7(Kd=0.001μM)并可以恢復(fù)?擾素I型信號(hào)轉(zhuǎn)導(dǎo)。RBN-2397有潛??于研究晚期或轉(zhuǎn)移性實(shí)體腫瘤。IC50&TargetPARP-7PARP-73nM(IC50)1nM(Kd)體外研究RBN-2397(0.0001-100μM;24hours)inhibitscellsproliferationwithanIC50valueof20nMinNCI-H1373lungcancercells[2].RBN-2397(0.4nM-1μM;24hours)showsarestorationoftypeIIFNresponsebyanincreaseinSTAT1phosphorylationasadose-dependentmannerinNCI-H1373humanlungcancercells[2].RBN-2397(0.0001-1μM;24hours)inhibitscellMARylationinacellbiochemialassaywithanEC50valueof1nM[2].CellProliferationAssay[2]CellLine:NCI-H1373lungcancercellsConcentration:0.0001μM;0.001μM;0.001μM;0.1μM;1μM;10μM;100μMIncubationTime:24hoursResult:Blockedcellproliferation.WesternBlotAnalysis[2]CellLine:NCI-H1373lungcancercellsConcentration:0.4nM-1μMIncubationTime:24hoursResult:Increasedp-STAT1proteinexpression.體內(nèi)研究RBN-2397(oraladministration;3-100mg/kg;oncedaily;24-32days)inducestumor-specificadaptiveimmunememoryinCT26syngeneicmodelwithdurablecompleteresponsesinCT26tumor-bearingBALB/cmice[2].RBN-2397(oraladministration;3-100mg/kg;oncedaily;32days)causescompleteregressionsatthedose100mg/kgandexertsadose-dependenteffectsontumorgrowthatdoselevelsof≥30mg/kg[2].Thehalf-life(t1/2)ofRBN-2397invivois325mins[2].AnimalModel:CB17SCIDmicewithNCI-H1373xenografts[2]Dosage:3mg/kg,10mg/kg,30mg/kg,100mg/kgAdministration:Oraladministration;oncedaily;24-32daysResult:Decreasedtumorvolumeandexertedanti-tumoreffects.REFERENCES2/3MasterofSmallMolecules—您?邊的抑制劑?師www.MedChemE[1].RBN-2397-InhibitingPARP7,aKeymonoPARPCancerDependency[2].MelissaVasbinder,etal.RBN-2397:AFirst-in-ClassPARP7InhibitorTargetingaNewlyDiscoveredCancerVulnerabilityinStress-SignalingPathways.McePdfHeightCaution:Producthasnotbeenfullyvalidatedfor