JP-163-16 is a RelA/p65 PROTAC degrader. It selectively reduces the expression of RelA/p65 in cells via a proteasome-dependent mechanism. JP-163-16 induces apoptosis by inhibiting the NF-κB signaling pathway. This compound is applicable for research on RelA/p65-dependent tumors, such as chronic lymphocytic leukemia (CLL).

JP-163-16 (Compound 15d) exhibits significant cytotoxicity towards MEC-1 cells (LC₅₀ = 0.14 μM) and primary CLL cells (LC₅₀ = 0.23 μM) within a concentration range of 3.16-3162 nM over 48 hours. Its cytotoxic effects rely on cereblon expression, displaying weaker inhibition of RPMI-8226 cells (LC₅₀ = 0.68 μM). At concentrations of 0.1-5 μM over 48 hours, JP-163-16 significantly suppresses the growth of MDA-MB-231 cells (LC₅₀ = 2.9 μM) and induces apoptosis by reducing RelA/p65 levels in a proteasome-dependent manner. The compound shows much lower toxicity towards primary B lymphocytes (LD₅₀ = 19.1 μM) and T lymphocytes (LD₅₀ = 36.4 μM). Additionally, JP-163-16 selectively decreases RelA/p65 levels in MEC-1 cells with minimal impact on RelB and cRel at 0-1 μM over 24 hours.