LC Labs/C6556 CHIR99021, Free Base, >99%/C6556/50 mg

• CHIR99021specificallyinhibitsglycogensynthasekinase-3β(GSK3β,IC50=5nm)andGSK3α(IC50=10nm),inhibitspreadipocytedifferentiation(IC50=0.3µM),possiblybyblockinginductionofC/EBPαandPPARγ,andmimicsWntsignalingin3T3-L1preadipocytes.Bennett,C.N.,etal."RegulationofWntsignalingduringadipogenesis."J.Biol.Chem.277:30998-31004(2002).
• CHIR99021showedhighlyselectiveinhibitionofGSK-3αandGSK-3β,withIC50sof10nMand6.7nM,respectively.ItshowedaKiof9.8nMforGSK-3β.However,itexhibitedanIC50of8800nMforCDC2.CHIR99021activatesglycogensynthaseinCHO-IRcellswithEC50of763nM.ZDFratsdisplayinsulinresistance,glucoseintolerance,andmildhyperglycemia.Intheserats,asingleoraldoseofCHIR99021rapidlyreducedplasmaglucosewhileplasmainsulinremainedatorbelowcontrollevels.ZDFratstreatedwithCHIR99021showedsignificantlyimprovedglucosetolerancewithnosignificantdifferencesinplasmainsulinlevelscomparedwithcontrolanimals.Ring,D.B.,etal."Selectiveglycogensynthasekinase3inhibitorspotentiateinsulinactivationofglucosetransportandutilizationinvitroandinvivo."J.Biol.Chem.277:30998-31004(2002)Diabetes52:588-595(2003).
• Alsterpaullone,kenpaullone,SB214763,andSB415286notonlyinhibitedGSK-3potentlybutalsoblockedCDKs.Incontrast,CHIR99021showed350-foldselectivitytowardGSK-3comparedtoCDKs.GSK-3isanimportantintermediateinthepathwayfromtheinsulinreceptortotheThymine-richInsulinResponseElement(TIRE).RegulationofgenetranscriptionbyinsulintotallydependsonGSK-3inhibition.Finlay,D.,etal."Glycogensynthasekinase-3regulatesIGFBP-1genetranscriptionthroughthethymine-richinsulinresponseelement."BMCMol.Biol.5:15(2004).
• CHIR99021inducedosteoblastogenesis,increasedmineralization,andinhibitedadipogenesisinST2cells.BennettC.N.,etal."RegulationofosteoblastogenesisandbonemassbyWnt10b."Proc.Natl.Acad.Sci.USA102:3324-3329(2005).
• GSK-3isaregulatorofpancreaticbetacellreplicationandsurvival,andtheGSK3inhibitorCHIR99021increasedtherateofINS-1Ebetacellreplication.Mussmann,R.,etal."InhibitionofGSK3promotesreplicationandsurvivalofpancreaticbetacells."J.Biol.Chem.282:12030-12037(2007).
• Soldforlaboratoryormanufacturingpurposesonly;notforhuman,veterinary,food,orhouseholduse.
• ThisproductisofferedforR&Duseinaccordancewith(i)35USC271(e)+A13(1)intheU.S.;(ii)Section69.1ofJapanesePatentLawinJapan;(iii)Section11,No.2oftheGermanPatentActof1981inGermany;(iv)Section60,Paragraph5boftheU.K.PatentsActof1977intheU.K.;(v)Sections55.2(1)and55.2(6)andothercommonlawexemptionsofCanadianpatentlaw;(vi)Section68BofthePatentsActof1953inNewZealandtogetherwiththeamendmentofsamebytheStatutesAmendmentBillof2002;(vii)suchrelatedlegislationand/orcaselawasmaybeorbecomeapplicableintheaforementionedcountries;and(viii)suchsimilarlawsandrulesasmayapplyinvariousothercountries.
• Notavailableinsomecountries;notavailabletosomeinstitutions;notavailableforsomeuses.

M.W.465.34
C22H18Cl2N8
[252917-06-9]

Storage

Storeatorbelow-20ºC

Solubility

SolubleinDMSOat25mg/mLwithwarming;verypoorlysolubleinethanol;verypoorlysolubleinwater;maximumsolubilityinplainwaterisestimatedtobeabout20-40µM;buffers,serum,orotheradditivesmayincreaseordecreasetheaqueoussolubility

Disposal

A