Pam2CSK4 (trifluoroacetate salt)

Pam₂CSK₄ is a synthetic bacterial lipopeptide and an agonist of the toll-like receptor 2 (TLR2).¹ It is selective for the TLR2/TLR6 heterodimer over TLR2/TLR1 (EC₅₀s = 0.015 and 4.12 ng/ml, respectively, in reporter assays using human receptors). Pam₂CSK₄ increases the levels of inducible nitric oxide synthase (iNOS) and the production of nitric oxide (NO) in RAW 264.7 macrophages when used at a concentration of 100 ng/ml.² It stimulates osteoclast formation, induces gingival inflammation, and decreases alveolar bone mass in a mouse model of periodontitis when administered at a dose of 5 µg/animal.³ Pam₂CSK₄ (10 µg/vaccine), when used as an adjuvant, reduces parasite burden and enhances the response to antigen, as measured by IgG levels, in a mouse model of lymphatic filariasis induced by B. malayi.⁴

1.Irvine, K.L., Hopkins, L.J., Gangloff, M., et al.The molecular basis for recognition of bacterial ligands at equine TLR2, TLR1 and TLR6Vet. Res.44(1)50(2013) 2.Kulsantiwong, P., Pudla, M., Srisaowakarn, C., et al.Pam2CSK4 and Pam3CSK4 induce iNOS expression via TBK1 and MyD88 molecules in mouse macrophage cell line RAW264.7Inflamm. Res.66(10)843-853(2017) 3.de Souza, J.A.C., MagalhÁes, F.A.C., de Oliveira, G.J.P.L., et al.Pam2CSK4 (TLR2 agonist) induces periodontal destruction in miceBraz. Oral. Res.34e012(2020) 4.Halliday, A., Turner, J.D., GuimarÃes, A., et al.The TLR2/6 ligand PAM2CSK4 is a Th2 polarizing adjuvant in Leishmania major and Brugia malayi murine vaccine modelsParasit. Vectors996(2016)