KTX-951 is an orally active PROTAC degrader of IRAK4 and IMiD (Ikaros/Aiolos) substrates ( K d = 3.5 nM). KTX-951 induces IRAK4 degradation, and the degradation efficiency is independent of IRAK4 binding affinity. The DC 50 values of KTX-951 for IRAK4 , Ikaros and Aiolos are 18 nM, 14 nM and 13 nM, respectively. The IC 50 of KTX-951 against OCl-Ly10 CTG is 35 nM. KTX-951 exhibits antitumor activity. (Pink: IRAK4 ligand ( HY-48932 ); Blue: Cereblon ligand ( HY-10984 ); Black: linker ( HY-W382009 )).
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