Description | AZD7648isapotentinhibitorofDNA-PKwithanIC50of0.6nMinbiochemicalassayandmorethan100-foldselectiveagainst396otherkinases. | ||
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Targets |
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Invitro | AZD7648inhibitsIR-inducedDNA-PKS2056autophosphoryalationwithanIC50=92nMinA549non-smallcelllungcancer(NSCLC)cells.InA549cells,AZD7648(≥1µM)incombinationwith2GyIRfor48hoursleadstoasignificantaccumulationofcellsarrestedintheG2/Mofthecellcycle,a4-foldincreaseinmicronucleiformation,and3-foldinductionofγH2AX,pATMS1981and53BP1fociformationcomparedwithIRalone[2]. | ||
Invivo | AZD7648isapotentandhighlyselectiveDNA-PKinhibitor,withgoodcrystallinesolubility,permeABIlityandmetabolicstability,goodbioavailabilityandpredictablepharmacokineticsinpreclinicalspecies,andpotentknockdownofpRPAandregressionsinmurinexenograftmodelswhencombiningwitholapariborrADIation[1]. |