MT-802

MT-802 is a BTK PROTAC degrader. MT-802 degrades wild-type BTK (DC₅₀ = 14.6 nM) and BTK mutants including E41K, C481S (DC₅₀ = 14.9 nM), C481R, C481Y, C481T, C481F, L528W, and inhibits their Y223 phosphorylation. BI-4732 can be used for the study of Ibrutinib (HY-10997)-resistant chronic lymphocytic leukemia (CLL). (Pink: BTK ligand (HY-150885), Blue: CRBN Ligand (HY-14658), Black: Linker (HY-141371), E3 ligase ligand-linker conjugate (HY-176340))^[1][2]. IC50 & Target:DC50: 1 nM (BTK)^[1]. In Vitro:MT-802 shows binding affinity to BTK with an IC₅₀ of 18.11 nM and to CRBN with an IC₅₀ of 1.258 μM in TR-FRET-based binding assays^[1].
MT-802 (0.1-10 μM, 24 h) degrades wild-type BTK and BTK mutants including E41K, C481S, C481R, C481Y, C481T, C481F, L528W, and inhibits their Y223 phosphorylation, but fails to degrade T474I mutant BTK in HEK293 cells with transient expression of BTK variants^[1].
MT-802 (0.25-250 nM, 24 h) induces degradation of BTK in NAMALWA cells and induces equivalent degradation of WT BTK (DC₅₀ = 14.6 nM) and C481S mutant BTK (DC₅₀ = 14.9 nM) in WT BTK XLAs cells and C481S BTK XLAs cells, respectively^[2].
MT-802 (0.01-10 μM, 24 h) degrades BTK and does not induce degradation of IKZF1 and IKZF3 transcription factors in primary cells from CLL samples^[2].
MT-802 (1 μM, 0.0042-4 h) degrades WT BTK and C481S mutant BTK, and reduces the level of phosphorylated BTK (pBTK, Y223) in WT BTK XLAs cells and C481S BTK XLAs cells, respectively^[2].