GS25-B005

GS25-B005 is a highly potent, orally bioavailable molecular glue degrader (MGD) that selectively targets the hematopoietic-specific signaling protein VAV1 for proteasomal degradation [POS0900]. Developed by GeneScience Pharmaceuticals, a subsidiary of Changchun High-Tech Industry (Group), GS25-B005 is designed to treat T- and B-cell-mediated autoimmune diseases and chronic inflammatory disorders, such as inflammatory bowel disease (IBD). VAV1 is a Rho-family guanine nucleotide exchange factor mainly expressed in immune cells, acting downstream of both T-cell and B-cell receptors [POS0900]. By inducing the degradation of VAV1, GS25-B005 inhibits T-cell and B-cell activation, proliferation, and cytokine release [POS0900]. In preclinical studies, GS25-B005 demonstrated sub-nanomolar degradation potency (DC50) in human cells, outperforming competitor molecules like MRT-6160, and showed robust in vivo target degradation and inhibition of antibody production in mouse models [POS0900].