Zeteletinib-BOS-172738-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEZeteletinibCat.No.:HY-139590CASNo.:2216753-97-6Synonyms:BOS-172738;DS-5010分⼦式:C₂₅H₂₃F₃N₄O₄分⼦量:500.47作⽤靶点:RET;PDGFR作⽤通路:ProteinTyrosineKinase/RTK储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:100mg/mL(199.81mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM1.9981mL9.9906mL19.9812mL5mM0.3996mL1.9981mL3.9962mL10mM0.1998mL0.9991mL1.9981mL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%saline1/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:≥2.5mg/mL(5.00mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(5.00mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.00mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Zeteletinib(BOS-172738;DS-5010)⼀种⼝服有效的，选择性RET激酶抑制剂，对RET具有纳尔效⼒，对VEGFR2具有>300倍的选择性。Zeteletinib对野⽣型RET、RETV804M/Lgatekeeper突变体和最常见的致癌RET突变体M918T显⽰出较⾼的效⼒。Zeteletinib具有强⼤的抗肿瘤活性。IC50&TargetPDGFR2体外研究Inbiochemicalassaysof106kinases,RETandplatelet-derivedgrowthfactorreceptor(PDGFR)alpha/betawereinhibitedmorethan80%by193nMZeteletinib(BOS-172738;DS-5010).TheIC50valuesofZeteletinibagainstRET,RET-GKm(V804L)weresingledigitnano-molarevenunderaconditionofhighconcentrationofATP;besidesitagainstKDRwasmorethan1000nM[1].体内研究InaBa/F3-RETsubcutaneoustumormodel,Zeteletinib(BOS-172738;DS-5010)dosingat10mg/kgtwicedaily(bid)inducestumorregression[1].InanLC2/adNSCLCxenograftmodel,whichhastheRET-CCDC6fusiongene,Zeteletinibdosingat1mg/kgthricedaily(tid)inducedtumorregression[1].REFERENCES[1].YasuyukiKaneta,etal.AbstractB173:PreclinicalcharacterizationandantitumorefficacyofDS-5010,ahighlypotentandselectiveRETinhibitor.MOLECULARCANCERTHERAPEUTICS.January2018,Volume17,Issue1.[2].PatrickSchoffski,etal.BOS172738,ahighlypotentandselectiveRETinhibitor,forthetreatmentofRET-alteredtumorsincludingRET-fusion+NSCLCandRET-mutantMTC:Phase1studyresults.JournalofClinicalOncology39,no.15_suppl(May20,2021)3[3].KyawZThein,etal.PrecisiontherapyforRET-alteredcancerswithRETinhibitors.TrendsCancer.2021Dec;7(12):1074-1088.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedicalappli