T-1101-tosylate-TAI-95-tosylate-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemET-1101tosylateCat.No.:HY-120356ACASNo.:2250404-95-4Synonyms:TAI-95tosylate分⼦式:C₃₁H₃₁N₅O₆S₃分⼦量:665.8作⽤靶点:Apoptosis作⽤通路:Apoptosis储存⽅式:4°C,sealedstorage,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoisture)溶解性数据体外实验DMSO:62.5mg/mL(93.87mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM1.5020mL7.5098mL15.0195mL5mM0.3004mL1.5020mL3.0039mL10mM0.1502mL0.7510mL1.5020mL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,awayfrommoisture)。-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:≥2.08mg/mL(3.12mM);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:≥2.08mg/mL(3.12mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性T-1101tosylate(TAI-95tosylate)⼀种具有抗肿瘤活性的Hec1/Nek2抑制剂。T-1101tosylate对正常细胞、激酶和hERG⽆抑制效果[1]。IC50&TargetHec1/Nek2[1]体外研究T-1101tosylateshowspotentinvitroantiproliferativeactivity(IC50:14.8-21.5nM)[1].T-1101tosylatedisruptstheHec1/Nek2protein–proteininteractioninthecells[1].T-1101tosylate(1μM;3-2424hours)decreasesthelevelofNek2inatime-dependentmanner[1].T-1101tosylate(1µM;24hours)inducesapoptosis[1].T-1101tosylatereducesamountsofcell-cyclerelatedproteinscyclinA1,cyclinB1,andcyclinD1[1].ApoptosisAnalysis[1]CellLine:HeLacellsConcentration:1µMIncubationTime:24hoursResult:Increasedtheamountofapoptoticmarkerproteinscleavedcaspase-3andPARPanddecreasedtheamountofantiapoptoticproteinsMcl-1andXIAPinHeLacells.WesternBlotAnalysis[1]CellLine:K562cellsConcentration:1μMIncubationTime:3hours,6hours,16hours,24hoursResult:LoweredthelevelofNek2inatime-dependentmanner.体内研究T-1101tosylateshowsgoodoralbioavailabilityandthermalstability[1].Oralco-administrationofT-1101tosylate(2.5mg/kg;p.o.;twiceperday)halvesthedoseofsorafenib(25mg/kgto12.5mg/kg)requiredtoexhibitcomparableinvivoactivitytowardsHuh-7xenografts[1].T-1101tosylate(2.5mg/kg;p.o.;twiceperday)showssignificantinvivoactivityinmicebearingvarioushumancancerxenografts[1].AnimalModel:SCIDmicebearinghumanHuh-7,BT-474,MCF-7,andMDA-MB-231xenografts[1]Dosage:25mg/kg,50mg/kg2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEAdministration:Oraladministration;twiceperday;28daysResult:Showedsignificantinvivoactivityinmicebearingvarioushumancancerxenografts.REFERENCES[1].ChuangSH,etal.DiscoveryofT-1101tosylateasafirst-in-classclinicalcandidateforHec1/Nek2inhibitionincancertherapy.EurJMedChem.2020Apr1;191:112118.McePdfHeightCaution:Producthasnotbeenfullyvalida