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

Catalog No.GC10273

Pam3CSK4 (Pam3CysSerLys4) est un lipopeptide triacylé synthétique et un agoniste du ligand TLR2/TLR1 avec une EC50 de 0,47 ng/mL.

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Pam3CSK4 Chemical Structure

Cas No.: 112208-00-1

Taille Prix Stock Qté
1mg
122,00 $US
En stock
5mg
495,00 $US
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Sample solution is provided at 25 µL, 10mM.

Product has been cited by 1 publications

Product Documents

Quality Control & SDS

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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.

Background

Pam3CSK4 (Pam3CysSerLys4) est un lipopeptide triacylé synthétique et un agoniste du ligand TLR2/TLR1 avec une EC50 de 0,47 ng/mL[10]. Pam3CSK4 imite l'extrémité amino acylée des LP bactériens. Les LP bactériens sont une famille de composants pro-inflammatoires de la paroi cellulaire présents dans les bactéries Gram-positives et Gram-négatives. Ces LP bactériens sont reconnus par TLR2, un récepteur qui joue un rôle clé dans la détection d'une gamme diversifiée de motifs moléculaires associés aux pathogènes (PAMPs). La reconnaissance de Pam3CSK4, un lipopeptide triacylé, est médiée par TLR2 qui coopère avec TLR1 à travers leur domaine cytoplasmique pour induire la cascade de signalisation conduisant à l'activation du NF-κB [1].

Dans les cellules HepaRG, Pam3CSK4 présente une large activité antivirale contre le VHB. Pam3CSK4 est un ligand TLR1/2 bien caractérisé et spécifique[2]. L'effet anti-VHB de Pam4CSK4 dépend de TLR1/2 et de son adaptateur MyD88 ; cibler TLR1 ou TLR6 avec des siARN spécifiques affecte l'expression en boucle avant de TLR2 dans le contexte de l'activation par Pam3CSK4, mais l'invalidation de TLR1 a conduit à une réduction de l'effet inhibiteur de Pam3CSK4. Le faible niveau fonctionnel de TLR2 était suffisant pour produire l'effet thérapeutique de Pam3CSK4[4,5]. Ceci confirme que Pam3CSK4 signale probablement via des hétérodimères TLR1/2 dans les hépatocytes[3].

L'activation des hétérodimères TLR2/1 par Pam3CSK4 médie la douleur et les démangeaisons, tandis que l'activation des hétérodimères TLR2/6 par l'acide lipotéichoïque (LTA) ou le glycan de levure conduit aux démangeaisons[9]. En tant que régulateur cutané, IL-13 active les neurones sensoriels et participe à l'initiation de la dermatite atopique et des démangeaisons[7]. IL-13 seul n'a pas entraîné une augmentation significative du nombre de grattages, mais TLR2 favorise la signalisation d'IL-13 dans les neurones sensoriels. La signalisation innée de TLR2 favorise non seulement les démangeaisons et la douleur, mais convertit également une dermatite médiée par des cellules TH2 transitoires en inflammation persistante qui est liée à la DA humaine chronique[8]. Chez les souris prétraitées avec Pam3CSK4, l'injection d'IL-13 a provoqué environ deux fois plus de grattages que l'injection du véhicule[6]. Pam3CSK4 renforce le transitoire calcique induit par IL-13 dans les neurones sensoriels et élève les comportements similaires aux démangeaisons induits par IL-13 chez la souris.

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.

Chemical Properties

Cas No. 112208-00-1 SDF
Synonymes 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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Average Rating: 5 ★★★★★ (Based on Reviews and 38 reference(s) in Google Scholar.)

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