Gingipains are a family of proteases secreted by Porphyromonas gingivalis. Members of gingipains (family C25) strictly cleave peptide bonds with either Arg-Xaa or Lys-Xaa at the cleavage site, and Arg-gingipain and Lys-gingipain are the responsible enzymes. Lys-gingipain (Kgp) is encoded by a single gene, kgp. It is a major virulence factor of P. gingivalis. Lys-gingipain participates in many P. gingivalis-mediated pathogenic processes by binding various targets and importantly, cleaving multiple proteins. The development of inhibitors of this enzyme will therefore be of critical importance to combat this disease. In addition, Gingipain also has a potential role in Alzheimer’s disease.

Atuzaginstat (also known as COR388) is an effective small-molecule bacterial protease lysine gingipain inhibitor. Atuzaginstat selectively blocks P. gingivalis toxicity and reduces bacterial load. In addition, Shirin Arastu-Kapur et al. found that Porphyromonas gingivalis infection increased the expression of PD-L1 on Het-1A cells within 24 hours after infection. Atuzaginstat treatment significantly decreases the PD-L1 expression in immortalized non-transformed esophageal cell line. Furthermore, lysine gingipain inhibition is able to inhibit the non-canonical activation ofβ-catenin and down regulation of classical wnt pathway effectors at both the mRNA and protein level. Most importantly, Atuzaginstat has the potential for Alzheimer’s disease research.

To sum up, Atuzaginstat is a potent protease lysine gingipain inhibitor, which has the potential for Alzheimer’s disease research.


[1] Arastu-Kapur, S, et al. Journal for Immuno Therapy of Cancer. 2020; 8(Suppl 3): A715-A715.

[2] Cortexyme Presents an Update and Baseline Data from the Phase 2/3 GAIN Trial of Atuzaginstat at CTAD 2020, the Clinical Trials on Alzheimer’s Disease Conference.