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 BTK degradation in JeKo-1 cells at 1.6-1000 nM over 24 hours (DC50 = 7.0 nM) [1] and exhibits metabolic stability at 100 and 1000 nM (half-life = 145 minutes) [1]. At 100 nM, BTK degradation over 12 hours is inhibited by MG-132 (5.0 μM) [1]. It does not degrade IKZF1 and GSPT1 but shows some activity against IKZF3 at 1.6-1000 nM over 24 hours [1]. PROTAC BTK Degrader-5 demonstrates antiproliferative effects after 72 hours on OCI-ly10 (IC50 = 2.3 nM), TMD8 (4.5 nM), JeKo-1 (38.1 nM), and BTK C481S Ba/F3 cells (86.0 nM), outperforming Ibrutinib (IC50 = 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].