GPR35 inhibitor CT3001

An orally bioavailable inhibitor of G-protein coupled receptor 35 (GPR35) and formulated with polyethylene glycol 400 (PEG400), with potential antineoplastic activity. Upon oral administration, GPR35 inhibitor CT3001 targets, binds to and inhibits the activity of GPR35. As GPR35 promotes the activity of the transcription coactivators yes-associated protein 1 (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), the inhibition of GPR35 decreases YAP/TAZ activity and prevents the interaction between YAP/TAZ and the transcription factor TEAD (TEA domain). This may inhibit YAP/TAZ-TEAD promoted gene transcription involved in tumor cell proliferation, angiogenesis and survival, and may inhibit tumor cell proliferation. In addition, CT3001 may abrogate YAP/TAZ-mediated immunosuppression in the tumor microenvironment (TME) and may suppress regulatory T cells (Tregs) and increase cytotoxic T-lymphocyte (CTL) tumor infiltration. This may promote an anti-tumor immune response. GPR35, an oncogenic protein and member of the G protein-coupled receptor family, is overexpressed in a variety of tumors. It promotes tumor immune escape and mediates YAP/TAZ oncogenic activation. Pegylation increases the half-life of this agent.