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Medchemexpress/LY2835219(Synonyms: ABEMACICLIB; CDK4/6 dual inhibitor)/HY-16297/200mg188bio精品生物—专注于实验室精品爆款的电商平台 - 蚂蚁淘旗下精选188款生物医学科研用品
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Medchemexpress/LY2835219(Synonyms: ABEMACICLIB; CDK4/6 dual inhibitor)/HY-16297/200mg

LY2835219aselectiveCDK4/6inhibitorwithIC50valuesof2nMand10nMforCDK4andCDK6,respectively.

CustomerValidation

  • Nature.2017Aug24;548(7668):471-475.
  • MolCell.2017Oct19;68(2):336-349.e6.
  • NatCommun.2017Jun27;8:15916.
  • CancerRes.2016Nov15;76(22):6723-6734.
  • BiochimBiophysActa.2017Nov20;1865(2):354-363.
  • MolOncol.2017Aug;11(8):1035-1049.
  • Oncotarget.2017Jun27;8(40):67422-67438.
  • BiochemPharmacol.2017Jan15;124:29-42.
  • HarvardMedicalSchoolLINCSLIBRARY
Description

LY2835219aselectiveCDK4/6inhibitorwithIC50valuesof2nMand10nMforCDK4andCDK6,respectively.

IC50&Target

IC50:2nM(CDK4),10nM(CDK6)[3]

InVitro

LY2835219reducescellviABIlitywiththeIC50valuesrangingfrom0.5μMto0.7μM,inhibitsAktandERKsignalingbutnotmTORactivationatheadandnecksquamouscellcarcinoma(HNSCC)cells[1].LY2835219showsinhibitiononA375R1-4,M14R,andSH4RwithEC50valuesrangingfrom0.3to0.6μM;LY2835219inhibitstheproliferationoftheparentalA375andresistantA375RV1andA375RV2cellswithsimilarpotencieswithIC50valuesof395,260,and463nM,respectively[2].LY2835219inhibitsCDK4andCDK6withlownanomolarpotency,inhibitsRbphosphorylationresultinginaG1arrestandinhibitionofproliferation,anditsactivityisspecificforRb-proficientcells[3].

InVivo

LY2835219(45mg/kg,p.o.)incombinationwitheverolimuscausesacooperativeantitumoreffectinHNSCCxenografttumor[1].LY2835219(45or90mg/kg,p.o.)showssignificanttumorgrowthinhibitioninanA375xenograftmodel[2].

References
  • [1].KuBM,etal.TheCDK4/6inhibitorLY2835219haspotentactivityincombinationwithmTORinhibitorinheadandnecksquamouscellcarcinoma.Oncotarget.2016Mar22;7(12):14803-13.

    [2].YadavV,etal.TheCDK4/6inhibitorLY2835219overcomesvemurafenibresistanceresultingfromMAPKreactivationandcyclinD1upregulation.MolCancerTher.2014Oct;13(10):2253-63.

    [3].GelbertLM,etal.PreclinicalcharacterizationoftheCDK4/6inhibitorLY2835219:in-vivocellcycle-dependent/independentanti-tumoractivitiesalone/incombinationwithgemcitabine.InvestNewDrugs.2014Oct;32(5):825-37.

    [4].WuT,etal.Effectofabemaciclib(LY2835219)onenhancementofchemotherapeuticagentsinABCB1andABCG2overexpressingcellsinvitroandinvivo.BiochemPharmacol.2017Jan15;124:29-42.

KinaseAssay
[1]

Cells(5×103)areplatedin96wellplates.Cellsaretreatedthenextdayfor24to48hoursandthenassessedforcaspase-3activitybyCaspase-Glo-3/7Assay,aspermanufacturer"sinstructionsandaluminescenceplatereader.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

CellAssay
[1]

LY2835219isdissolvedinDMSOtoa10mMconcentration. 

Cellsareseededina96-wellplate,allowedtoadhereovernight,andtreatedwithDMSOcontrol(0.1%v/v)ortheindicatedcompoundsfor72h.CellviabilityandproliferationaredeterminedusingaCellCountingKitaccordingtothemanufacturer"sinstructions.TheinteractionbetweenLY2835219andmTORinhibitorisdeterminedusingCompuSyn.Combinationindex(CI)valuesof1indicatesandadditivedruginteraction,whereasaCIof<1=""is=""synergistic=""and=""a=""ci=""of="">1isantagoNISTic.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

AnimalAdministration
[1]

LY2835219isdissolvedin1%HECin20mMphosphatebuffer.

Six-week-oldBALB/cfemalenudemiceareinjectedsubcutaneouslywithOSC-19(1×106)cells.Whentumorsizesreachapproximately100mm3,micearerandomizedbytumorsizeandsubjectedtoeachtreatment.Atleast5micepertreatmentgroupareincluded.Eachgroupofmiceisdosedviadailyoralgavagewithvehicle,LY2835219(45mg/kg/dor90mg/kg/d),Everolimus(5mg/kg/d),oracombinationofboth.TheLY2835219isdissolvedin1%HECin20mMphosphatebuffer(pH2.0).Tumorsizeandbodyweightaremeasuredtwiceweekly.Tumorvolumesarecalculatedusingthefollowingformula:V=(L×W2)/2(L,Length;W,width).Micearegavagedafinaltimeonday14andsacrificedthefollowingday.ThetumorsareremovedforWesternblotandimmunohistochemistry.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

References
  • [1].KuBM,etal.TheCDK4/6inhibitorLY2835219haspotentactivityincombinationwithmTORinhibitorinheadandnecksquamouscellcarcinoma.Oncotarget.2016Mar22;7(12):14803-13.

    [2].YadavV,etal.TheCDK4/6inhibitorLY2835219overcomesvemurafenibresistanceresultingfromMAPKreactivationandcyclinD1upregulation.MolCancerTher.2014Oct;13(10):2253-63.

    [3].GelbertLM,etal.PreclinicalcharacterizationoftheCDK4/6inhibitorLY2835219:in-vivocellcycle-dependent/independentanti-tumoractivitiesalone/incombinationwithgemcitabine.InvestNewDrugs.2014Oct;32(5):825-37.

    [4].WuT,etal.Effectofabemaciclib(LY2835219)onenhancementofchemotherapeuticagentsinABCB1andABCG2overexpressingcellsinvitroandinvivo.BiochemPharmacol.2017Jan15;124:29-42.

MolecularWeight

602.7

Formula

C₂₈H₃₆F₂N₈O₃S

CASNo.

1231930-82-7

Storage
Powder-20°C3years
 4°C2years
Insolvent-80°C6months
 -20°C1month
Shipping

RoomtemperatureincontinentalUS;mayvaryelsewhere

Solvent&Solubility

H2O:≥250mg/mL

LY2835219isdissolvedin1%HECin20mMphosphatebuffer(pH2.0)andadministeredorallybygavage(finalvolume0.2mL)[4].

*"<1 mg/ml"="" means="" slightly="" soluble="" or="" insoluble.="" "≥"="" means="" soluble,="" but="" saturation="">

References
  • [1].KuBM,etal.TheCDK4/6inhibitorLY2835219haspotentactivityincombinationwithmTORinhibitorinheadandnecksquamouscellcarcinoma.Oncotarget.2016Mar22;7(12):14803-13.

    [2].YadavV,etal.TheCDK4/6inhibitorLY2835219overcomesvemurafenibresistanceresultingfromMAPKreactivationandcyclinD1upregulation.MolCancerTher.2014Oct;13(10):2253-63.

    [3].GelbertLM,etal.PreclinicalcharacterizationoftheCDK4/6inhibitorLY2835219:in-vivocellcycle-dependent/independentanti-tumoractivitiesalone/incombinationwithgemcitabine.InvestNewDrugs.2014Oct;32(5):825-37.

    [4].WuT,etal.Effectofabemaciclib(LY2835219)onenhancementofchemotherapeuticagentsinABCB1andABCG2overexpressingcellsinvitroandinvivo.BiochemPharmacol.2017Jan15;124:29-42.

Purity:99.87%

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