KTX-951 is an orally active IRAK4 and IMiD (Ikaros/Aiolos) substrates PROTAC degrader. KTX-951 has DC50 of 13 nM, 14 nM and 13 nM for IRAK4, Ikaros and Aiolos, respectively. TX-951 has antitumor activity.(Pink: IRAK4 ligand-12 (HY-48932); Black: Linker (HY-W382009); Blue: CRBN Ligand Pomalidomide (HY-10984))[1]
KTX-951 (10 mg/kg;Oral administration) has an oral bioavailability (F%) of 22% and an AUC of 2.6 μM hr in rats[1].
KTX-951 (10 mg/kg;Oral administration) has an oral bioavailability (F%) of 57% in dogs[1].
IRAK4: 3.5 nM (Kd); IRAK4: 18 nM (DC50)
[1] Walker D H, et al. Degraders targeting both IRAK4 and IMiD substrates show combinatorial effects leading to broader activity with durable and complete regressions in MYD88 mutant lymphoma xenografts in vivo. Cancer Research, 2020, 80(16_Supplement): 5222-5222.