Pam2Cys  (Synonyms: Dipalmitoyl-S-glyceryl-cysteine; S-[2,3-Bis(palmitoyloxy)propyl]cysteine)

Pam2Cys (Dipalmitoyl-S-glyceryl-cysteine; S-[2,3-Bis(palmitoyloxy)propyl]cysteine) is a TLR2 agonist and immunostimulant. Pam2Cys binds to TLR2 to activate dendritic cells and trigger the TLR2-dependent NF-κB signaling pathway. Pam2Cys also induces dendritic cell maturation by upregulating the expression of cell surface MHC II molecules. Pam2Cys activates innate immune signaling pathways, drives pro-inflammatory and antimicrobial responses, enhances the expression of macrophage activation markers, increases phagocytic activity, induces the release of IL-12 and pro-inflammatory cytokines, and polarizes macrophages into a pro-inflammatory, antimicrobial phenotype without interfering with IL-10-induced macrophage polarization. Pam2Cys also serves as the lipid moiety in synthetic lipopeptide vaccines and possesses self-adjuvant properties. Pam2Cys enhances the immunogenicity of conjugated peptide segments and induces cellular and humoral immune responses. However, it does not activate CD4 T cells in mouse splenocyte cultures when used alone. Pam2Cys activates pulmonary TLR2 signaling pathways, triggers innate immune responses, recruits neutrophils and macrophages, induces the secretion of various cytokines, alleviates symptoms and damages associated with influenza A virus infection in mice without impairing adaptive immunity. Pam2Cys can be used in studies related to tuberculosis and influenza A virus infection^[1][2][3][4].

The Pam2Cys-containing lipopeptide construct (0.025-0.25 nmol/mL; 5 h) potently activates NF-κB signaling through TLR2 in HEK293 cells^[1].
Pam2Cys (10-100 ng/mL; 24 h) increases the phagocytic activity of porcine monocyte-derived macrophages, with a stronger effect at the higher dose^[2].
Pam2Cys (10-100 ng/mL; 4 h, 8 h, 24 h) upregulates the gene expression of IL-1β, IL-6, TNF-α, and IL-12p40 at 4, 8, and 24 h, and IL-10 at 4 and 8 h, in porcine monocyte-derived macrophages^[2].
Pam2Cys (10-100 ng/mL; 4 h, 8 h, 24 h) upregulates the gene expression of multiple IFN-α subtypes (IFN-α1, IFN-α2, IFN-α5/6, IFN-α9 at 8 h; IFN-α16 at 24 h), downregulates IFN-α3 at 24 h, and does not alter IFN-β expression, in porcine monocyte-derived macrophages^[2].
Pam2Cys (10-100 ng/mL; 4 h, 8 h, 24 h) downregulates the gene expression of TLR3, TLR4, TLR5, TLR7, TLR8, and TLR9 in porcine monocyte-derived macrophages at multiple time points (4, 8, 24 h) post-treatment^[2].
Pam2Cys (50-100 ng/mL; 72 h) alone does not activate CD4 T cells from L91-immunized mice^[3].
Pam2Cys (10 nmol; 24 h) induced primary mouse lung cells to exhibit significantly elevated levels of IL-6, IL-10, MCP-1, IFN-γ, and TNF-α, with no change in IFN-α levels^[4].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Pam2Cys-containing lipopeptide vaccine (40 nmol; s.c.; 2 doses (days 0 and 28)) induces strong anti-LHRH antibody titres and renders 100% of treated female BALB/c mice infertile^[1].
Immunization with the Pam2Cys-conjugated construct L91 (20-10 nmol per animal; i.p. or s.c., i.p.) induces Th1-skewed dendritic cell activation, robust and enduring CD4 T-cell memory responses, and significantly better protection against Mycobacterium tuberculosis aerosol challenge in mice than BCG, with a 40% reduction in lung bacterial burden relative to BCG^[3].
Pam2Cys (20 nmol; i.n.; single dose) provides dose-dependent viral load reduction of up to 88% in mice challenged with mild IAV, with efficacy persisting for at least 7 days post-administration^[4].
Pam2Cys (20 nmol; i.n.; single dose) prophylaxis preserves the development of functional, memory-phenotype IAV-specific CD8⁺ T cells in mice, with enhanced responses in the spleen and reduced but detectable responses in the lungs^[4].
Pam2Cys (20 nmol; i.n.; single dose) reduces IAV viral load by over 99% in the trachea and lungs of BALB/c mice, with no effect on nasal turbinate infection^[4].
Pam2Cys (20 nmol; i.n.; single dose) provides TLR2-dependent, type 1 interferon-independent protection against virulent IAV in mice, with 92% survival and significant weight loss reduction^[4].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

672.05

C₃₈H₇₃NO₆S

656831-18-4

Solid

White to off-white

O=C([C@@H](N)CSCC(OC(CCCCCCCCCCCCCCC)=O)COC(CCCCCCCCCCCCCCC)=O)O

Room temperature in continental US; may vary elsewhere.

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

• [1]. Zeng W, et al. Structural requirement for the agonist activity of the TLR2 ligand Pam2Cys. Amino Acids. 2010;39(2):471-480.

  [2]. Franzoni G, et al. Targeting Toll-Like Receptor 2: Polarization of Porcine Macrophages by a Mycoplasma-Derived Pam2cys Lipopeptide. Vaccines (Basel). 2021;9(7):692. Published 2021 Jun 23.  [Content Brief]

  [3]. Gowthaman U, et al. Promiscuous peptide of 16 kDa antigen linked to Pam2Cys protects against Mycobacterium tuberculosis by evoking enduring memory T-cell response. J Infect Dis. 2011;204(9):1328-1338.

  [4]. Tan AC, et al. Intranasal administration of the TLR2 agonist Pam2Cys provides rapid protection against influenza in mice. Mol Pharm. 2012;9(9):2710-2718.  [Content Brief]