Molecular Glue/PROTAC Optimization Kit for GSPT2

The Molecular Glue/PROTAC(R) Optimization Kit for GSPT2 is an AlphaLISA(R) assay designed for the testing and profiling of Molecular Glues (MG) and PROTACs (proteolysis targeting chimeras) targeting GSPT2 (G1 to S phase transition 2). The kit comes with enough recombinant GSPT2, biotinylated Cereblon-DDB1 complex, and an optimized GSPT buffer. This kit also contains the GSPT degrader CC-885, and the Cereblon ligand pomalidomide. The Molecular Glue/PROTAC(R) of interest is incubated with biotinylated Cereblon/DDB1 complex and GSPT2, bringing them into proximity. The Cereblon/DDB1 complex is recognized by the Streptavidin donor bead. GSPT2 contains a GST-tag that binds to the Glutathione AlphaLISA(TM) acceptor bead. Upon excitation of the donor bead, a singlet oxygen is generated by the bead. The singlet oxygen excites the acceptor bead, which emits light proportionally to the level of interaction between GSPT2 and Cereblon/DDB1 complex. Need us to run inhibitor screens or profile your compounds against PROTAC(R) Optimization for GSPT2-Cereblon Binding? Check out our PROTACs (R) & Protein Degradation Services. GSPT2 (G1 to S phase transition 2), also known as eRF3b, is an essential translation-termination factor that became a key substrate for cereblon (CRNB)-based molecular glues (MGs) such as CC-885 and CC-90009. These compounds bind cereblon and trigger the E3 ligase to recruit and ubiquitinate GSPT2, leading to its rapid proteasomal degradation. Cereblon is the substrate-binding component of the E3 protein ligase complex DDB1 (damage specific DNA binding protein 1)-CUL4A (cullin 4)-RBX1 (ring-box 1), which is involved in the ubiquitination and proteasomal degradation of target proteins. CRBN has become a target of choice for the development of many PROTACs with therapeutical interest. Loss of GSPT2 disrupts translational fidelity and induces strong antiproliferative effects, particularly in AML (acute myeloid lymphoma) and other sensitive cancer types. As a result, GSPT2 is now considered a high-value target in the field of targeted protein degradation (TPD). The development of these molecular glues and PROTACS (proteolysis targeting chimeras) opens new avenues in cancer therapy.