The combination of GCKi and iberdomide synergistically exerts anti-MM effects. (A) H929 cells proliferation was assessed after treatment with the combination of TL4-12 and iberdomide at indicated doses for 4 days. (B) The CI value was analyzed by CompuSyn software. (C-D) MM.1S cells proliferation was assessed and the combination of TL4-12 and iberdomide at indicated doses for 4 days (C), and CI value was analyzed by CompuSyn (D). (E-F) LP1 cells proliferation was assessed after treatment with the combination of TL4-12 and iberdomide at indicated doses for 4 days (E), and CI value was analyzed by CompuSyn (F). (G) H929 and MM.1S cells were treated with TL4-12 and iberdomide at the indicated concentrations for 4 days. Cell apoptosis was detected by flow cytometry after Annexin V and 7-AAD staining. (H) MM cells were treated with TL4-12 (MM.1S and U266, 5 μM; H929 and LP-1, 2 μM) and/or iberdomide (MM.1S and U266, 1 nM; H929 and LP-1, 30 nM) for 24 hours. The protein expression level of c-MYC, IKZF3, and IKZF1 were detected by western blot using β-actin as a loading CT. GCKi is GCK inhibition.