Table 1.
IMiD/CELMoDs currently used in clinical practice with structure, known neosubstrates, and IC50 (as evaluated by protein competitive binding assay, displacing a Cy-5-labeled CELMoD analog from CRBN)
| IMiD/CELMoD | Structure | Reported neosubstrates in myeloma cells | Approximate CRBN-binding affinity IC50 (μM) |
|---|---|---|---|
| Thalidomide |  | Ikaros, Aiolos, PLZF, RNF166, SALL4, TP63, ZFP91, ZNF276, ZNF653, ZNF692, and ZNF827 | |
| Lenalidomide |  | Ikaros, Aiolos, CK1α, FAM83F, RAB28, RNF166, SALL4, WIZ, ZFP91, ZNF276, ZNF653, ZNF692, and ZNF827 | 1.5 |
| Pomalidomide |  | Ikaros, Aiolos, ARID2, DTWD1, E4F1, FAM83F, GZF1, PATZ1, PLZF, RAB28, RNF166, SALL4, ZBTB39, ZFP91, ZNF98, ZNF198, ZNF276, ZNF517, ZNF582, ZNF653, ZNF654, ZNF692, ZNF787, and ZNF827 | 1.2 |
| Iberdomide |  | Ikaros, Aiolos, IKZF2, IKZF4, ZFP91, ZNF653, ZNF98, and ZNF827 | 0.06 |
| Mezigdomide |  | Ikaros, Aiolos, and ZFP91 | 0.03 |
| IMiD/CELMoD | Structure | Reported neosubstrates in myeloma cells | Approximate CRBN-binding affinity IC50 (μM) |
|---|---|---|---|
| Thalidomide | | Ikaros, Aiolos, PLZF, RNF166, SALL4, TP63, ZFP91, ZNF276, ZNF653, ZNF692, and ZNF827 | |
| Lenalidomide | | Ikaros, Aiolos, CK1α, FAM83F, RAB28, RNF166, SALL4, WIZ, ZFP91, ZNF276, ZNF653, ZNF692, and ZNF827 | 1.5 |
| Pomalidomide | | Ikaros, Aiolos, ARID2, DTWD1, E4F1, FAM83F, GZF1, PATZ1, PLZF, RAB28, RNF166, SALL4, ZBTB39, ZFP91, ZNF98, ZNF198, ZNF276, ZNF517, ZNF582, ZNF653, ZNF654, ZNF692, ZNF787, and ZNF827 | 1.2 |
| Iberdomide | | Ikaros, Aiolos, IKZF2, IKZF4, ZFP91, ZNF653, ZNF98, and ZNF827 | 0.06 |
| Mezigdomide | | Ikaros, Aiolos, and ZFP91 | 0.03 |
Data are given as evaluated by protein competitive binding assay, displacing a Cy-5-labeled cereblon binding compound from CRBN.11,12,31,71,80,82-88,90
IC50, 50% inhibitory concentration.