Medchemexpress/Ruxolitinib phosphate(Synonyms: INCB018424 phosphate; INCB 018424 phosphate; INCB-018424 phosphate; Ruxolitini

Ruxolitinib(phosphate)isthefirstpotentJAK1/2inhibitorwithIC₅₀valuesof3.3nM/2.8nM,morethan130-foldselectivityforJAK1/2versusJAK3.

IC50:3.3nM(JAK1),2.8nM(JAK2)

Ruxolitinib(INCB018424)potentlyandselectivelyinhibitsJAK2V617F-mediatedsignalingandproliferation.RuxolitinibinhibitsthegrowthofHELcellswithEC₅₀of186nM.RuxolitinibmarkedlyincreasesapoptosisinBa/F3-EpoR-JAK2V617Fcellsystem,andinhibitshematopoieticProgenitorcellproliferationinprimaryMPNpatientsamples^[1].

Ruxolitinib(180mg/kg,p.o.)reducesthetumorburdenofmiceinoculatedwithJAK2V617F-expressingcellswithoutcausinganemiaorlymphopenia^[1].

• [1].Quintas-CardamaA,etal.PreclinicalcharacterizationoftheselectiveJAK1/2inhibitorINCB018424:therapeuticimplicationsforthetreatmentofmyeloproliferativeneoplasms.Blood,2010,115(15),3109-3117.

  [2].FleischmanAG,etal.TheCSF3RT618ImutationcausesalethalneutrophilicneoplasiainmicethatisresponsivetotherapeuticJAKinhibition.Blood.2013Nov21;122(22):3628-31.

Ruxolitinibphosphateisdissolvedin0.2%DMSO.

Cellsareseededat2000/wellofwhitebottom96-wellplates,treatedwithcompoundsfromDMSOstocks(0.2%finalDMSOconcentration),andincubatedfor48hoursat37°Cwith5%CO₂.ViABIlityismeasuredbycellularATPdeterminationusingtheCell-TiterGloluciferasereagentorviablecellcounting.Valuesaretransformedtopercentinhibitionrelativetovehiclecontrol,andIC₅₀ curvesarefittedaccordingtononlinearregressionanalysisofthedatausingPRISMGraphPad.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

Ruxolitinibphosphateisdissolvedinvehicle(5%dimethylacetamide,0.5%methocellulose).

Micearefedstandardrodentchowandprovidedwithwateradlibitum.Ba/F3-JAK2V617Fcells(10⁵ permouse)areinoculatedintravenouslyinto6-to8-week-oldfemaleBALB/cmice.Survivalismonitoreddaily,andmoribundmicearehumanelykilledandconsidereddeceasedattimeofdeath.Treatmentwithvehicle(5%dimethylacetamide,0.5%methocellulose)orRuxolitinib(INCB018424)beginswithin24hoursofcellinoculation,twicedailybyoralgavage.HematologicparametersaremeasuredusingaBayerAdvia120analyzed,andstatisticalsignificanceisdeterminedusingDunnetttesting.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

• [1].Quintas-CardamaA,etal.PreclinicalcharacterizationoftheselectiveJAK1/2inhibitorINCB018424:therapeuticimplicationsforthetreatmentofmyeloproliferativeneoplasms.Blood,2010,115(15),3109-3117.

  [2].FleischmanAG,etal.TheCSF3RT618ImutationcausesalethalneutrophilicneoplasiainmicethatisresponsivetotherapeuticJAKinhibition.Blood.2013Nov21;122(22):3628-31.

404.36

C₁₇H₂₁N₆O₄P

1092939-17-7

RoomtemperatureincontinentalUS;mayvaryelsewhere

DMSO:≥31mg/mL;H₂O:5.4mg/mL(Needultrasonicorwarming)

Ruxolitinibphosphateisdissolvedin5%dimethylacetamide,0.5%methylcellulose^[2].

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

• [1].Quintas-CardamaA,etal.PreclinicalcharacterizationoftheselectiveJAK1/2inhibitorINCB018424:therapeuticimplicationsforthetreatmentofmyeloproliferativeneoplasms.Blood,2010,115(15),3109-3117.

  [2].FleischmanAG,etal.TheCSF3RT618ImutationcausesalethalneutrophilicneoplasiainmicethatisresponsivetotherapeuticJAKinhibition.Blood.2013Nov21;122(22):3628-31.