PROTAC BTK Degraders-5 (Compound 3e) is a selective Bruton's tyrosine kinase (BTK) degrader with a DC50 of 7.0 nM in JeKo-1 cells, demonstrating specificity by not affecting CRBN neosubstrates. It also exhibits antiproliferative effects on various lymphoma cell lines, underscoring its potential application in chronic lymphoid malignancies research.

PROTAC BTK Degrader-5 (Compound 3e) induces degradation of BTK in JeKo-1 cells at concentrations ranging from 1.6 to 1000 nM over 24 hours, with a DC50 value of 7.0 nM [1]. At concentrations of 100 and 1000 nM, the compound demonstrates metabolic stability with a half-life of 145 minutes [1]. The BTK degradation induced by PROTAC BTK Degrader-5 at 100 nM over 12 hours is effectively inhibited by the proteasome inhibitor MG-132 at 5.0 μM [1]. PROTAC BTK Degrader-5 shows no degradation activity against IKZF1 and GSPT1, while possessing some degradation activity against IKZF3 at concentrations from 1.6 to 1000 nM over 24 hours [1]. After 72 hours of treatment, PROTAC BTK Degrader-5 exhibits anti-proliferative effects on OCI-ly10, TMD8, JeKo-1, and BTK C481S Ba/F3 cells, with IC50 values of 2.3, 4.5, 38.1, and 86.0 nM, respectively, outperforming Ibrutinib whose IC50 values are 4.5, 4.7, 79.8, and 1546.0 nM respectively [1].

PROTAC BTK Degrader-5, administered at a single dose of 2 mg/kg via intravenous injection, exhibits stable metabolism in mice [1].