PMX-205 is a cyclic hexapeptide that acts as a potent antagonist of C5a receptor (C5aR; IC₅₀ = 31 nM).¹ It is orally active and blocks inflammatory signaling and symptoms in animal models of colitis and allergic asthma.^2,3 PMX-205 is also brain penetrant and reduces neuroinflammation and neurodegeneration in an animal model of Alzheimer’s disease.⁴

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1.March, D.R.,Proctor, L.M.,Stoermer, M.J., et al. Potent cyclic antagonists of the complement C5a receptor on human polymorphonuclear leukocytes. Relationships between structures and activity. Mol. Pharmacol. 65(4), 868-879 (2004).

2.Jain, U.,Woodruff, T.M. and Stadnyk, A.W. The C5a receptor antagonist PMX205 ameliorates experimentally induced colitis associated with increased IL-4 and IL-10. Br. J. Pharmacol. 168(2), 488-501 (2013).

3.Staab, E.B.,Sanderson, S.D.,Wells, S.M., et al. Treatment with the C5a receptor/CD88 antagonist PMX205 reduces inflammation in a murine model of allergic asthma. Int. Immunopharmacol. 21(2), 293-300 (2014).

4.Fonseca, M.I.,Ager, R.R.,Chu, S.-H., et al. Treatment with a C5aR antagonist decreases pathology and enhances behavioral performance in murine models of Alzheimer’s disease. J. Immunol. 183(2), 1375-1383 (2009).