20(S)camptothecinhasshownpromisingactivityagainstarangeoftumourtypes. ThisCPTderivativecausescelltoxicitybystABIlizingaternarycomplexbetweenthenuclearenzymetopoisomeraseI(topoI)anddouble-strandedDNA,leADIngtosingleanddoublestrandbreaks. TopoGENprovidesthisreagentasacontrolpoison/inhibitoroftopoisomeraseI. Forinvitrocleavagedetection,werecommendthatthedrugbetestedoverawiderangeofuMconcentrations;however,cleavagesarestronglyinfluencedbytheamountoftopoisomeraseinthereactionaswellasthetypeofassaybeingemployed(SDSK+vs.Radioac-tiveEndLabeledDNAvs.testingforplasmidcleavages). Notethatlargeamountsofenzymewillberequiredtodetectcleavagecomplex,comparedtoassaysthatmeasurecatalyticactivity.
MolecularFormula:C20H19N3O6
MolecularWeight:393.35
VialContents:
TG4102issuppliedalreadysUSPendedinDMSOat10mM(0.25ml)andisreadyforuse. Thedrugispre-testedandshowntoinducetopocleavagesusingpurifiedhumantopoisomerasefromTopoGEN.