Supplementary Figures S1-S16 from Golcadomide: An Oral CELMoD Agent Targeting IKZF1/3 for Diffuse Large B-cell Lymphoma

Supplementary Fig. 1. Golcadomide induced transition from CRBNopen to CRBNclosed for efficient recruitment and degradaion. Supplementary Fig. 2. Antiproliferative effect of golcadomide is mediated via CRBN-based IKZF1/3 degradation. Supplementary Fig. 3. Golcadomide is broadly active with potent cell autonomous antiproliferative activity. Supplementary Fig. 4. Antiproliferative effect of golcadomide is mediated via CRBN based IKZF1/3 degradation. Supplementary Fig. 5. Golcadomide demonstrated minimal broad cytotoxicity and reversible effects on neutrophil maturation. Supplementary Fig. 6. Golcadomide stimulated immune activation, reversed T cell exhaustion, and exhibited potent antitumor synergy with rituximab. Supplementary Fig. 7. Overview of different treatment conditions and technical replicates in the CRISPR screen. Supplementary Fig. 8. CRISPR screen identified genes and pathways that exacerbated or attenuated antiproliferative effects of golcadomide in SU-DHL-4 upon inactivation. Supplementary Fig. 9. KO of PRC2 complex components enhanced cell antiproliferation by golcadomide. Supplementary Fig. 10. Apoptosis induction is linked to the antiproliferative effects of golcadomide. Supplementary Fig. 11. NF-κB hyperactivation reduced golcadomide-induced DLBCL cell apoptosis. Supplementary Fig. 12. XPO1 inhibitor enhances antiproliferative effects of golcadomide. Supplementary Fig. 13. AMBRA1 knockout renders resistance to golcadomide via cyclin D3/CDK4/6/Rb axis in DLBCL. Supplementary Fig. 14. KCTD5 ameliorated the antiproliferative effects of golcadomide via GNG5. Supplementary Fig. 15. Chemical synthesis of golcadomide. Supplementary Fig. 16. Representative gating strategies for flow cytometry-based assays.