Pam2CSK4

Pam2CSK4 is a TLR2 agonist. Pam2CSK4 induces the expression of iNOS and NO in macrophage cell lines via TBK1 and MyD88 molecules. Pam2CSK4 activates the NF-κB and Bruton's tyrosine kinase signaling pathways in platelets, and promotes platelet-endothelial cell interactions. TLR2 activation triggered by Pam2CSK4 expands myeloid-derived suppressor cells (MDSCs) and suppresses anti-tumor immune responses in the tumor microenvironment. Pam2CSK4 acts as a Th2-polarizing adjuvant in mouse vaccine models against Leishmania major and Brugia malayi. Pam2CSK4 can be used in the research of various diseases, including thromboinflammatory diseases, sepsis, atherosclerosis, heart failure, influenza, lymphoma, melanoma, cutaneous leishmaniasis and lymphatic filariasis^{[1][2][3][4][5][6]}. In Vitro:Pam2CSK4 (100 ng/mL; 6-24 h) induces TLR2-mediated iNOS expression in RAW264.7 mouse macrophages, and this production depends on TBK1 and MyD88^[1].
Pam2CSK4 (100 ng/mL; 6-24 h) induces significant TLR2-mediated NO production in RAW264.7 murine macrophages, and this production is dependent on TBK1 and MyD88^[1].
Pam2CSK4 (1-10 μg/mL; 25 min at 37°C) induces concentration-dependent α-granule secretion and integrin α_IIbβ₃ activation in washed human platelets and platelets in citrated human whole blood^[2].
Pam2CSK4 (10 μg/mL; 6-45 min at 37°C) induces donor-dependent aggregation of washed human platelets under stirring conditions and enhances the adhesion of washed human platelets to collagen-coated surfaces^[2].
Pam2CSK4 (10 μg/mL; 2-10 min at 37°C) activates multiple signaling pathways in washed human platelets, including the Akt, PKC, NF-κB and MAPK (p38) pathways^[2].
Pam2CSK4 (10 μg/mL) induces dense granule secretion (ATP release) in washed human platelets, and this response depends on the TLR2, NF-κB and BTK signaling pathways^[2].
Pam2CSK4 (10 μg/mL; 4 h at 37°C) enhances the inflammatory response of HUVECs (characterized by upregulated ICAM-1 expression, increased IL-6 secretion and increased IL-8 secretion)^[2] only when co-cultured with washed human platelets.
Pam2CSK4 (10 μg/mL; 10 min at 37°C platelet pre-incubation, 10 min co-culture) enhances the adhesion of washed human platelets to untreated and TNF-α-stimulated HUVEC monolayers under static and physiologically relevant flow conditions^[2].
Pam2CSK4 is a potent dual TLR2 agonist for both human and murine sources. It induces NF-κB activity with an EC₅₀ of 67 pM, and can stimulate the production of various cytokines and chemokines^[3].
Pam2CSK4 (100 nM; 3 days) treatment of CD11b+Gr1+ myeloid-derived suppressor cells (MDSCs) from EG7 tumor-bearing mice dose-dependently inhibited antigen-induced OT-IT cell proliferation^[4]. In Vivo:Pam2CSK4 (50 nmol; i.v.; single dose) induces systemic TLR2-dependent accumulation of immunosuppressive CD11b⁺Gr1⁺ MDSCs and enhances MDSC survival in EG7 tumor-bearing mice^[4].
Pam2CSK4 (50 nmol; i.v.; single dose) induces accumulation of CD11b⁺Gr1⁺ MDSCs in spleens of B16D8 melanoma-bearing mice^[4].
Pam2CSK4 (10 μg; s.c.; two doses, 2 weeks apart) as an adjuvant with ALM exacerbates cutaneous leishmaniasis disease severity in female C57BL/6 mice and drives a predominantly Th2-type immune response characterized by elevated antigen-specific IgG1 levels^[6].
Pam2CSK4 (10 μg; s.c.; single dose) as an adjuvant with BmMfE induces significant protective immunity against B. malayi L3 challenge in male BALB/c mice, reducing parasite burden by 41% and driving robust Th2 cytokine production and antigen-specific antibody responses^[6].