QPCTL inhibitor (Insilico Medicine)

QPCTL inhibitor refers to a class of small molecule therapeutics, most notably the candidate ISM8207 developed by Insilico Medicine, designed to modulate the CD47-SIRPα immune checkpoint axis. The enzyme glutaminyl-peptide cyclotransferase-like (QPCTL) catalyzes the formation of N-terminal pyroglutamate on CD47, a modification critical for its binding to the signal regulatory protein alpha (SIRPα) on macrophages and other myeloid cells. By inhibiting QPCTL, these agents prevent the stabilization of the "don't eat me" signal on tumor cells, thereby enhancing macrophage-mediated phagocytosis and anti-tumor immunity. This mechanism is intended to overcome resistance in "cold" tumors that do not respond to standard T-cell-targeted therapies. As of 2024, Insilico Medicine's QPCTL inhibitor program is in Phase 1 clinical trials for the treatment of advanced solid tumors.

Other names

Glutaminyl-peptide cyclotransferase-like inhibitor