INNO-220 is an orally active, CRBN-dependent molecular glue degrader that targets CK1α. By degrading CK1α, INNO-220 induces cell cycle arrest at the G0/G1 phase and triggers apoptosis (Apoptosis). It disrupts the assembly and function of the CARD11/BCL10/MALT1 complex, inhibiting the NF-κB signaling pathway in T cells and lymphoma cells with activating mutations in CARD11. INNO-220 offers a novel direction for lymphoma research.

INNO-220 (Compound INNO-220) demonstrates broad-spectrum antiproliferative activity against wild-type p53 lymphoma cells at concentrations of 0.0001-10 μM over 72 hours. Its inhibition of IL-2 is dependent on CRBN within the same concentration range, but over 24-72 hours. INNO-220 also suppresses lymphoma cell growth by inducing apoptosis and causing cell cycle arrest at the G0/G1 phase at 2-1250 nM for 24 hours. At 50 nM for 8 hours, it modulates the p53/NF-κB signaling pathway in OCI-Ly3 and Z-138 cells. Additionally, INNO-220 at concentrations of 2-1250 nM for 6-24 hours activates p53 through CK1α degradation in OCI-Ly3, Z-138, and OCI-Ly19 cells.

INNO-220 (Compound INNO-220), administered orally at doses of 3-20 mg/kg daily for 43 days, can induce tumor regression in DLBCL and MCL xenograft models, inhibit NF-κB activity, and does not significantly alter mouse body weight, offering a new direction for lymphoma-related research.