Potent C5a receptor peptide antagonist (IC50 = 31 nM). Ameliorates experimentally-induced colon inflammation in mice. Reduces fibrillar amyloid deposits, decreases hyperphosphorylated tau levels and rescues cognitive function in a mouse model of Alzheimer's Disease. Orally active and brain penetrant.
CAT No: 10-101-154
CAS No:514814-49-4
Synonyms/Alias:PMX 205;514814-49-4;PMX-205;Hydrocinnamate-(orn-Pro-dcha-Trp-Arg);PMX205;DC25O3L7KZ;LP-16;UNII-DC25O3L7KZ;Cyclic hexapeptide complement C5a antagonist;N-[(3S,9S,12S,15R,18S)-15-(cyclohexylmethyl)-9-[3-(diaminomethylideneamino)propyl]-12-(1H-indol-3-ylmethyl)-2,8,11,14,17-pentaoxo-1,7,10,13,16-pentazabicyclo[16.3.0]henicosan-3-yl]-3-phenylpropanamide;ALS-205;CHEBI:144869;hydrocinnamate-cyclo(ornithyl-prolyl-D-cyclohexylalanyl-tryptophyl-arginyl);(5->1)-lactam-N(2)-(1-oxo-3-phenylpropyl)-L-ornithyl-L-prolyl-3-cyclohexyl-D-alanyl-L-tryptophyl-L-arginine;N-[(3R,6S,9S,15S,20aS)-9-(3-carbamimidamidopropyl)-3-(cyclohexylmethyl)-6-(1H-indol-3-ylmethyl)-1,4,7,10,16-pentaoxoicosahydropyrrolo[1,2-a][1,4,7,10,13]pentaazacyclooctadecin-15-yl]-3-phenylpropanamide;HC-[OP(D-Cha)WR];N-((3R,6S,9S,15S,20aS)-9-(3-carbamimidamidopropyl)-3-(cyclohexylmethyl)-6-(1H-indol-3-ylmethyl)-1,4,7,10,16-pentaoxoicosahydropyrrolo(1,2-a)(1,4,7,10,13)pentaazacyclooctadecin-15-yl)-3-phenylpropanamide;N-((3S,9S,12S,15R,18S)-15-(cyclohexylmethyl)-9-(3-(diaminomethylideneamino)propyl)-12-(1H-indol-3-ylmethyl)-2,8,11,14,17-pentaoxo-1,7,10,13,16-pentazabicyclo(16.3.0)henicosan-3-yl)-3-phenylpropanamide;C5a receptor peptide antagonist;GTPL5762;SCHEMBL12971708;EX-A5705;PVA81449;AKOS040735090;DA-56943;HY-110136;CS-0032991;G79478;851-045-5;N-((3R,6S,9S,15S,20AS)-6-((1H-indol-3-yl)methyl)-3-(cyclohexylmethyl)-9-(3-guanidinopropyl)-1,4,7,10,16-pentaoxoicosahydropyrrolo[1,2-a][1,4,7,10,13]pentaazacyclooctadecin-15-yl)-3-phenylpropanamide;
PMX 205 is a synthetic cyclic hexapeptide recognized for its potent and selective antagonistic activity against the complement component 5a receptor (C5aR1, also known as CD88). As a structurally optimized peptide compound, PMX 205 has become an invaluable tool in the field of immunology and inflammation research, enabling precise modulation of complement-mediated pathways. Its unique biochemical profile, including high receptor affinity and metabolic stability, has positioned it as a preferred reagent for dissecting the molecular mechanisms underlying complement system activation and its downstream effects. Researchers leverage PMX 205 in a variety of experimental models to explore the biological functions and pathophysiological roles of C5aR1, providing critical insights into innate immunity and inflammatory processes.
Complement Pathway Investigation: PMX 205 is extensively utilized in studies aiming to elucidate the role of the complement system, particularly the C5a-C5aR1 axis, in immune regulation and inflammatory signaling. By selectively blocking C5aR1, the peptide enables researchers to dissect the contribution of this receptor to cellular responses such as chemotaxis, cytokine release, and leukocyte activation. This targeted inhibition facilitates detailed analysis of complement-mediated signaling cascades in both in vitro and in vivo models, advancing our understanding of innate immune responses.
Inflammation and Immune Modulation Studies: As a highly specific C5aR1 antagonist, PMX 205 serves as a critical tool for probing the involvement of complement-derived anaphylatoxins in inflammatory disease models. Its application allows for the assessment of how C5aR1 signaling influences the recruitment and activation of immune cells, vascular permeability, and tissue injury. By modulating these pathways, investigators can delineate the cellular and molecular mechanisms that drive chronic or acute inflammation, supporting the development of new hypotheses in immunopathology research.
Peptide-Target Interaction Analysis: The defined structure and receptor selectivity of PMX 205 make it an excellent candidate for studies focused on peptide-receptor interactions. Researchers use it to characterize the binding dynamics, specificity, and downstream signaling events associated with C5aR1 antagonism. Such investigations contribute to broader efforts in structure-activity relationship (SAR) analysis, informing the design of next-generation peptide modulators and therapeutic candidates targeting complement receptors.
Cellular Signaling Pathway Dissection: PMX 205 is frequently employed to interrogate intracellular signaling events triggered by C5aR1 activation. By inhibiting receptor engagement, the peptide allows for the evaluation of downstream pathways such as MAPK, NF-κB, and PI3K/Akt in various cell types, including neutrophils, macrophages, and endothelial cells. This approach aids in mapping the complex signaling networks that govern immune cell function, apoptosis, and the resolution of inflammation.
Preclinical Model Development: In translational research settings, PMX 205 is instrumental in the development and validation of animal models for complement-driven diseases. Its use enables the selective blockade of C5aR1, thereby permitting the investigation of disease mechanisms and the assessment of potential intervention strategies in a controlled experimental context. The peptide's utility in these models provides essential data for advancing basic and applied research on immune-mediated pathologies.
Anti-complement therapies have not been advanced for treating the inflammatory bowel diseases (IBDs) despite a growing body of evidence that blocking C5a protects against induced colitis in rodents. The purpose of this study was to further build on this evidence by examining the efficacy, mechanism and specificity of a potent, non-competitive and orally active C5a receptor (CD88) antagonist, PMX205, in the dextran sulphate sodium (DSS) model of murine innate colitis.
Jain, U., Woodruff, T. M., & Stadnyk, A. W. (2013). The C5a receptor antagonist PMX205 ameliorates experimentally induced colitis associated with increased IL‐4 and IL‐10. British journal of pharmacology, 168(2), 488-501.
Allergic asthma is a chronic inflammatory airway disease arising from an aberrant immune response following exposure to environmental stimuli in genetically susceptible persons. The complement component 5 (C5)/C5a Receptor (C5aR/CD88) signaling pathway has been implicated in both experimental allergic asthma and human asthmatic disease. Targeting the C5a/C5aR signaling pathway in rodent models has been shown to either enhance or reduce allergic asthma consequences. Treatment with a recombinant humanized monoclonal antibody directed against C5 has shown unclear results in patients with asthma. The objective of this proof-of-concept animal study was to determine whether the low molecular weight C5aR peptidomimetic antagonist, PMX205, would reduce experimental allergic asthma consequences in mice. PMX205 or vehicle control was administered subcutaneously to BALB/c mice prior to and during standard ovalbumin (OVA) allergen sensitization and aerosolized challenge phases. PMX205 substantially reduced OVA-induced total cell (60%), neutrophil (66%) and eosinophil (65%) influxes in lavage fluid sampling. There were also significant reductions in OVA-induced lavage fluid IL-13 protein and lung Th2 cytokine gene expression with PMX205 administration. PMX205 treatment also diminished OVA-induced lung parenchyma cellular infiltration. PMX205 administration did not reduce OVA-induced serum IgE levels or epithelial mucous/goblet cell generation. There was no evidence of toxicity observed with PMX205 treatment in saline or OVA-challenged animals. These data provide evidence that pharmacologic blockade of C5aR by a low molecular weight antagonist (PMX205) reduces airway inflammatory cell and cytokine responses in experimental allergic asthma, and suggests that PMX205 might represent a novel therapeutic agent for reducing asthmatic outcomes.
Staab, E. B., Sanderson, S. D., Wells, S. M., & Poole, J. A. (2014). Treatment with the C5a receptor/CD88 antagonist PMX205 reduces inflammation in a murine model of allergic asthma. International immunopharmacology, 21(2), 293-300.
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