Name: Pam3CSK4
Brand: GlpBio
SKU: GC10273
Availability: InStock
Rating: 5 (38 reviews)

Product has been cited by 1 publications

Phytomedicine 108 (2023): 154489.

Product Documents

Quality Control & SDS

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Purity: >98.00%

Protocol

Cell experiment [1]:
Cell lines	HepaRG cell
Preparation Method	Indicated differentiated HepaRG cell lines were infected with HBV with 100 vge/cell. At day-7 post-infection , cells were treated twice with either Pam3CSK4 (100 ng/mL), IFNα (500 IU/mL), RG7834 (0.1 μM), or the nucleoside analogue lamivudine (3 TC; 1 μM) for a total exposure time of 6 days. Cells and supernatants were harvested for analyses at day-13 post-infection.
Reaction Conditions	100 ng/mL; 6 days
Applications	Pam3CSK4 was capable to inhibit HBV (genotype D) replication in dHepaRG cells. The levels of all HBV parameters analyzed, (including intracellular total HBV RNAs, viremia, and secretion of viral antigens) were significantly reduced even at very low concentration of Pam3CSK4. Pam3CSK4 was also capable to inhibit the replication of another HBV genotype (genotype C). thus suggesting a broad antiviral activity against HBV. Pam3CSK4 as a TLR2 agonist, is a potent anti-HBV agents. Pam3CSK4 inhibits RNA accumulation by both impairing HBV transcription and RNA stability. Pam3CSK4 decreases also cccDNA level via a FEN-1-dependent mechanism.
Animal experiment [2]:
Animal models	C57 BL/6 mice
Preparation Method	To analyse the influence of TLR2 heterodimer activation on IL-13-induced itch-like behaviour, C57 BL/6 mice were pre-administered with Pam3CSK4 (20 μg/100 μl sterilized water) by gavage every three days for 3 times . In another experiment, FSL-1 (0.3 mg/kg, 60 μl sterilized water) was intraperitoneally injected 14 h before IL-13 injection. Control mice were given sterilized water only. All of these mice were then intradermally injected with IL-13 (1 μg/10 μl) or vehicle into the left cheek. All the mice were video-recorded for 1 h for the analysis of scratching bouts.
Dosage form	Pam3CSK4 (20 μg/100 μl sterilized water) by gavage every three days for 3 times
Applications	As a cutaneous regulator, IL-13 activates sensory neurons and participates in the initiation of AD and itch. Pam3CSK4 enhances IL-13-induced calcium transient in sensory neurons and elevates IL-13-induced Itch-like behaviours in mice。
References: [1]. Desmares M, Delphin M,et,al. Insights on the antiviral mechanisms of action of the TLR1/2 agonist Pam3CSK4 in hepatitis B virus (HBV)-infected hepatocytes. Antiviral Res. 2022 Aug 10;206:105386. doi: 10.1016/j.antiviral.2022.105386. Epub ahead of print. PMID: 35963549. [2]. Xiao S, Lu Z, et,al. Innate immune regulates cutaneous sensory IL-13 receptor alpha 2 to promote atopic dermatitis. Brain Behav Immun. 2021 Nov;98:28-39. doi: 10.1016/j.bbi.2021.08.211. Epub 2021 Aug 13. PMID: 34391816.

Pam3CSK4 (Pam3CysSerLys4) es un lipopéptido sintético triacilado (LP) y un agonista del ligando TLR2/TLR1 con una EC50 de 0,47 ng/mL^[10]. Pam3CSK4 imita el amino terminal acilado de los LP bacterianos. Los LP bacterianos son una familia de componentes proinflamatorios de la pared celular que se encuentran tanto en bacterias Gram-positivas como Gram-negativas. Estos LPs bacterianos son reconocidos por TLR2, un receptor que desempeña un papel fundamental en la detección de diversos patrones moleculares asociados a patógenos (PAMPs). El reconocimiento de Pam3CSK4, un LP triacilado, está mediado por TLR2 que coopera con TLR1 a través de su dominio citoplasmático para inducir la cascada de señalización que lleva a la activación del NF-κB ^[1].

En células HepaRG, Pam3CSK4 muestra una amplia actividad antiviral contra el VHB. Pam3CSK4 es un ligando TLR1/2 bien caracterizado y específico^[2]. El efecto anti-VHB de Pam4CSK4 depende de TLR1/2 y su adaptador MyD88; la inhibición de TLR1 o TLR6 con siRNA específicos afecta la expresión feed-forward de TLR2 en el contexto de la activación por Pam3CSK4, pero la invalidación de TLR1 llevó a una reducción del efecto inhibitorio de Pam3CSK4. El bajo nivel funcional de TLR2 fue suficiente para producir el efecto terapéutico de Pam3CSK4^[4,5]. Esto confirma que probablemente Pam3CSK4 señala a través del heterodímero TLR1/2 en hepatocitos^[3].

La activación de los heterodímeros TLR2/1 por Pam3CSK4 media el dolor y la picazón, mientras que la activación de los heterodímeros TLR2/6 por ácido lipoteicoico (LTA) o glicano de levadura conduce a picazón^[9]. Como regulador cutáneo, IL-13 activa neuronas sensoriales y participa en la iniciación del AD y la picazón^[7]. La IL-13 sola no provocó un aumento significativo en el número de rascados, pero TLR2 promueve la señalización de IL-13 en las neuronas sensoriales. La señalización innata de TLR2 no solo promueve la picazón y el dolor sino que convierte una dermatitis mediada por células TH2 transitoria en inflamación persistente que está relacionada con el AD crónico humano^[8]. En ratones tratados previamente con Pam3CSK4, la inyección de IL-13 causó aproximadamente el doble de rascados que la inyección del vehículo^[6]. Pam3CSK4 mejora el transitorio del calcio inducido por IL-13 en las neuronas sensoriales y eleva los comportamientos similares a picores inducidos por IL-13 en ratones.

References:
[1]: Ozinsky A, Underhill DM, et,al.The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between toll-like receptors. Proc Natl Acad Sci U S A. 2000 Dec 5;97(25):13766-71. doi: 10.1073/pnas.250476497. PMID: 11095740; PMCID: PMC17650.
[2]: Lucifora J, Xia Y, et,al. Specific and nonhepatotoxic degradation of nuclear hepatitis B virus cccDNA. Science. 2014 Mar 14;343(6176):1221-8. doi: 10.1126/science.1243462. Epub 2014 Feb 20. PMID: 24557838; PMCID: PMC6309542.
[3]: K. Visvanathan, N.A. Skinner, et al. Regulation of Toll-like receptor-2 expression in chronic hepatitis B by the precore protein. Hepatology. doi:10.1002. 2006.
[4]: Xiao S, Lu Z, et,al. Innate immune regulates cutaneous sensory IL-13 receptor alpha 2 to promote atopic dermatitis. Brain Behav Immun. 2021 Nov;98:28-39. doi: 10.1016/j.bbi.2021.08.211. Epub 2021 Aug 13. PMID: 34391816.
[5]: Erickson S, Heul AV, et,al. New and emerging treatments for inflammatory itch. Ann Allergy Asthma Immunol. 2021 Jan;126(1):13-20. doi: 10.1016/j.anai.2020.05.028. Epub 2020 Jun 1. PMID: 32497711.
[6]: Oetjen LK, Mack MR, et,al. Sensory Neurons Co-opt Classical Immune Signaling Pathways to Mediate Chronic Itch. Cell. 2017 Sep 21;171(1):217-228.e13. doi: 10.1016/j.cell.2017.08.006. Epub 2017 Sep 7. PMID: 28890086; PMCID: PMC5658016.
[7]: Kaesler S, Volz T, et,al. Toll-like receptor 2 ligands promote chronic atopic dermatitis through IL-4-mediated suppression of IL-10. J Allergy Clin Immunol. 2014 Jul;134(1):92-9. doi: 10.1016/j.jaci.2014.02.017. Epub 2014 Apr 1. PMID: 24698321.
[8]: Liu T, Gao YJ, et,al. Emerging role of Toll-like receptors in the control of pain and itch. Neurosci Bull. 2012 Apr;28(2):131-44. doi: 10.1007/s12264-012-1219-5. PMID: 22466124; PMCID: PMC3347759.
[9]:Wang TT, Xu XY, et,al. Activation of Different Heterodimers of TLR2 Distinctly Mediates Pain and Itch. Neuroscience. 2020 Mar 1;429:245-255. doi: 10.1016/j.neuroscience.2020.01.010. Epub 2020 Jan 16. PMID: 31954829.
[10]:Irvine KL, Hopkins LJ, Gangloff M, Bryant CE. The molecular basis for recognition of bacterial ligands at equine TLR2, TLR1 and TLR6. Vet Res. 2013 Jul 4;44(1):50. doi: 10.1186/1297-9716-44-50. PMID: 23826682; PMCID: PMC3716717.

Cas No.	112208-00-1	SDF
Sinónimos	Pam3Cys-Ser-(Lys)4
Chemical Name	(2S,3Z,5S,6Z,8S,9Z,11S,12Z,14S,15Z,17R)-2,5,8,11-tetrakis(4-aminobutyl)-4,7,10,13,16-pentahydroxy-17-((Z)-(1-hydroxyhexadecylidene)amino)-14-(hydroxymethyl)-24-oxo-21-(palmitoyloxy)-23-oxa-19-thia-3,6,9,12,15-pentaazanonatriaconta-3,6,9,12,15-pentaen-1-oi
Canonical SMILES	CCCCCCCCCCCCCCC/C(O)=N/[C@@](/C(O)=N/[C@@](/C(O)=N/[C@@](/C(O)=N/[C@@](/C(O)=N/[C@@](/C(O)=N/[C@@](C(O)=O)([H])CCCCN)([H])CCCCN)([H])CCCCN)([H])CCCCN)([H])CO)([H])CSCC(OC(CCCCCCCCCCCCCCC)=O)([H])COC(CCCCCCCCCCCCCCC)=O
Formula	C₈₁H₁₅₆N₁₀O₁₃S	M.Wt	1510.24
Solubility	50 mg/mL in DMSO ( Need ultrasonic); 16.67 mg/mL in Water ( Needultrasonic)	Storage	Store at -20°C
General tips	Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition	Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

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		1 mg	5 mg	10 mg
	1 mM	0.6621 mL	3.3107 mL	6.6215 mL
	5 mM	0.1324 mL	0.6621 mL	1.3243 mL
	10 mM	0.0662 mL	0.3311 mL	0.6621 mL

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Pam3CSK4 (Synonyms: Pam3Cys-Ser-(Lys)4)

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