QPCTL inhibitor

Blacksmith Medicines is developing a small molecule inhibitor of the metalloenzyme glutaminyl-peptide cyclotransferase-like protein (QPCTL) for use in cancer immunotherapy. QPCTL is responsible for the post-translational modification (pyroglutamylation) of the N-terminus of CD47, which is essential for its binding to Signal-regulatory protein alpha (SIRPα) on myeloid cells. By inhibiting QPCTL, the drug disrupts the 'don't eat me' signal mediated by the CD47-SIRPα innate immune checkpoint, thereby enhancing phagocytosis of tumor cells. Additionally, QPCTL modifies the chemokine CCL2 (MCP-1), and its inhibition reduces the recruitment of immunosuppressive cells to the tumor microenvironment. The program is currently in preclinical development in collaboration with Roche, leveraging Blacksmith's proprietary fragment-based drug discovery platform for metalloenzymes.

Other names

QPCTLglutaminyl-peptide cyclotransferase-like protein inhibitor