Translation termination factor GSPT1 is overexpressed and oncogenic in several cancers. GSPT1 is currently being explored as a therapeutic target for the treatment of acute myeloid leukemia. Molecular glues such as certain new CRBN modulators have shown the ability to induce selective degradation of GSPT1. CC-90009 (Eragidomide, Table ), structurally optimized from CC-885 , is the first rationally designed clinical candidate driven by the molecular glue-degrading mechanism. Currently, CC-90009 is the first CRBN-mediated protein degrader in Phase I clinical trials for treatment of relapsed/refractory acute myeloid leukemia. The sulfonamides SJ6986 and SJ7023 discovered by cell-based phenotypic screening of a library, have shown antiproliferative activities in two leukemia cell lines. Both compounds were identified as CRBN binders to recruit GSPT protein forming ternary complexes and further inducing GSPT1/2 degradation. BTX-1188 and MG-277 (Table ) induce the degradation of GSPT1 to achieve their potent anticancer activity. MG-277 is a powerful antitumor agent suppressing tumor cell growth in a p53independent manner. BTX-1188 is a leading molecular glue drug candidate in Phase I clinical trials for treating acute myeloid leukemia and myelodysplastic syndrome. It is worth to point out that BTX-1188 is discovered to degrade GSPT1, IKZF, and CK1α and is expected to kill tumor cells and simultaneously modulate the immune system, resulting in better efficacy and potentially fewer side effects. ZXH-161 (Table ) is a leading drug candidate exhibiting better potency and selectivity in GSPT1 degradation.