ICE Bioscience Posters

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KRAS molecular glue is an innovative small-molecule drug designed to target the KRAS mutant protein. It works by binding to cyclophilin A (CYPA) within the cell, thereby reshaping the surface of CYPA. This modification enables CYPA to bind with KRAS-GTP, forming a stable ternary complex. The formation of this complex effectively disrupts the interaction be- tween KRAS-GTP and its downstream effector proteins, ultimately inhibiting the oncogenic signaling pathways driven by KRAS.

ICE has developed a comprehensive screening and evaluation platform for KRAS molecular glues, which includes a series of biochemical and cellular-level assays. For example, the plat- form utilizes biochemical and biophysical methods for the screening of POI binders, detec- tion of KRAS(ON)/CypA/cRAF binary complexes, and KRAS(ON)/CypA ternary complexes. It also incorporates cell-based functional assays, such as 2D/3D cell proliferation and detection of ERK phosphorylation, a marker associated with signaling pathways. In addition, the plat- form offers p-ERK and 2D/3D panel assay. The table below summarizes and presents some of the data from ICE.