Molecular Glue/PROTAC Optimization Kit for KRAS (G12D)

The Molecular Glue/PROTAC(R) Optimization Kit for KRAS (G12D) is an AlphaLISA(R) assay designed for the testing and profiling of Molecular Glues (MG) and PROTACs (proteolysis targeting chimera) targeting KRAS (G12D) (Kirsten rat sarcoma mutation G12D). The kit comes with enough recombinant KRAS (G12D), biotinylated Cereblon-DDB1 complex, and an optimized KRAS buffer. This kit also contains the PROTAC KRAS Degrader-3, and the Cereblon ligand pomalidomide. Figure 1. Schematic representation of the mechanism of Molecular Glue/PROTAC(R) Optimization Kit for KRAS (G12D). The Molecular Glue/PROTAC(R) of interest is incubated with biotinylated Cereblon/DDB1 complex and KRAS (G12D), bringing them into proximity. The Cereblon/DDB1 complex is recognized by the Streptavidin AlphaLISA(TM) acceptor bead. KRAS (G12D) contains a His-tag that binds to the Nickel donor bead. Upon excitation of the donor bead, a singlet oxygen is generated. The singlet oxygen excites the acceptor bead, which emits light proportionally to the level of interaction between KRAS (G12D) and Cereblon/DDB1 complex. Need us to run inhibitor screens or profile your compounds against PROTAC(R) Optimization for GSPT1-Cereblon Binding? Check out our PROTACs (R) & Protein Degradation Services. It is well established that RAS mutations are responsible for more than 30% of human cancers. KRAS(G12D) is the most common mutation (33%) among KRAS mutant tumors. The G12D mutation favors the activated (GTP-bound) state of KRAS, amplifying signaling pathways that lead to oncogenesis. KRAS(G12D) is one of the most common oncogenic drivers in cancers such as pancreatic, colorectal, and lung adenocarcinomas, making it an important therapeutic target. Previously considered as "undruggable", KRAS (G12D) is now a high-value target in the field of targeted protein degradation (TPD). PROTAC (proteolysis targeting chimera) KRAS Degrader-3 represents a TPD strategy, designed to bind mutant KRAS(G12D) and recruit an E3 ubiquitin ligase. This induces ubiquitination of KRAS, marking it for proteasomal degradation rather than simple inhibition. The development of new molecular glues (MGs) and PROTACs opens new avenues in cancer therapy.