Extended Data Fig. 6: SB-405483 differentially modulates degradation of CRBN neosubstrates in the presence of monovalent degraders.

(a) Structures and reporter cell line targets of select orthosteric ligands tested in reporter cell line screen. (b–d) Neosubstrate degradation with indicated orthosteric ligands in the presence and absence of 10 µM SB-405483 treated for 24 h: (b) CK1α-HiBiT (c) IKZF1/3(ZF2)-GFP (d) IKZF2(ZF2)-GFP (e) Levels of SALL4(ZF1,2)-GFP in HEK293T reporter cell line treated with SB-405483 and orthosteric ligands relative to orthosteric ligand alone. (f) Degradation of indicated neosubstrate after treatment with lenalidomide in the presence or absence of 10 µM SB-405483 for 24 h. (g) Degradation of indicated neosubstrate after treatment with avadomide in the presence or absence of 10 µM SB-405483 for 24 h. (h) Degradation of indicated neosubstrate after treatment with mezigdomide in the presence or absence of 10 µM SB-405483 24 h. Data are mean ± s.e and error propagation were performed using the delta method. All flow cytometry data is representative of n = 3 biologically independent samples.