PMX 53 (Synonyms: 3D53) |
Katalog-Nr.GC50176
One-Click Copy Product Info
|
PMX 53 (3D53) ist ein synthetisches Peptid und ein potenter und oral aktiver Antagonist des Komplement-C5a-Rezeptors (CD88) mit einem IC50 von 20 nM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 219639-75-5
Sample solution is provided at 25 µL, 10mM.
_1-3.$$$39978408@51.jpg');)
_1-9.$$$38538795@65.jpg');)
_1-9.$$$39112701@51.jpg');)
_1-7.$$$37316672@70.jpg');)
_366-372.$$$36198801@70.jpg');)
.$$$38565142@65.jpg');)
_1867-1883.$$$33248023@67.jpg');)
_eads6055.$$$39977546@45.jpg');)
_eadm9805.$$$40080571@45.jpg');)
_eadj3020.$$$39666821@45.jpg');)
_1-20.$$$39757301@28.jpg');)
_1-24.$$$38898113@28.jpg');)
_273-287.$$$36806353@46.jpg');)
_1-16.$$$37156877@44.jpg');)
_1-19.$$$37460805@44.jpg');)
_1291-1307.$$$34518654@46.jpg');)
PMX 53 is a potent, cell-permeable, and orally active C5a receptor (CD88) antagonist with an IC50 value of 20nM[1]. PMX 53 specifically binds to C5aR1, blocking the interaction between complement C5a and its receptor, thereby inhibiting C5a-induced inflammatory responses such as myeloperoxidase (MPO) release and neutrophil chemotaxis. PMX 53 also acts as a low-affinity agonist for MrgX2 and can stimulate MrgX2-mediated mast cell degranulation at higher concentrations[1, 2]. PMX 53 is commonly used in research on inflammatory mechanisms in autoimmune diseases, sepsis, neurodegenerative diseases, and psoriasis[3].
In vitro, pre-incubation of C57BL/6J mouse neutrophils with PMX 53 (10μM) for 1h, followed by stimulation with recombinant murine C5a (0.1μM) for 3h, inhibited C5a-induced NETosis[4]. The addition of PMX 53 (50, 100, 150nM) to the culture medium of THP-1 and HL-60 cells prior to treatment with LukS-PV (1μM) for 24h led to a concentration-dependent suppression of LukS-PV-induced apoptosis[5].
In vivo, intravenous administration of PMX 53 (1mg/kg) via the femoral vein 30min before ischemia in Sprague-Dawley rats significantly reduced MPO activity in spinal cord tissue 48h after reperfusion[6]. Oral administration of PMX 53 (10mg/kg/day) to C57BL/6 mice, starting 2 days before intracerebral hemorrhage and continuing for 5 days, significantly decreased mRNA levels of TNF-α, IL-6, and iNOS in perihematomal tissues[7]. Subcutaneous injection of PMX 53 (3mg/kg) 30min before seizure stimulation in fully kindled CD1 mice reduced the proportion of mice experiencing stage 5 seizures by 50%[8].
References:
[1] SUBRAMANIAN H, KASHEM S W, COLLINGTON S J, et al. PMX-53 as a dual CD88 antagonist and an agonist for Mas-related gene 2 (MrgX2) in human mast cells[J]. Molecular pharmacology, 2011, 79(6): 1005-1013.
[2] DICK J, GAN P Y, FORD S L, et al. C5a receptor 1 promotes autoimmunity, neutrophil dysfunction and injury in experimental anti-myeloperoxidase glomerulonephritis[J]. Kidney international, 2018, 93(3): 615-625.
[3] KÖHL J. Drug evaluation: the C5a receptor antagonist PMX-53[J]. Current opinion in molecular therapeutics, 2006, 8(6): 529-538.
[4] CHEN Y, LI X, LIN X, et al. Complement C5a induces the generation of neutrophil extracellular traps by inhibiting mitochondrial STAT3 to promote the development of arterial thrombosis[J]. Thrombosis journal, 2022, 20(1): 24.
[5] ZHANG P, YU W W, PENG J, et al. LukS-PV induces apoptosis in acute myeloid leukemia cells mediated by C5a receptor[J]. Cancer medicine, 2019, 8(5): 2474-2483.
[6] DONG Q, SUN L, PEN L, et al. PMX53 protects spinal cord from ischemia-reperfusion injury in rats in the short term[J]. Spinal Cord, 2016, 54(4): 254-258.
[7] LI G, FAN R M, CHEN J L, et al. Neuroprotective effects of argatroban and C5a receptor antagonist (PMX53) following intracerebral haemorrhage[J]. Clinical & Experimental Immunology, 2014, 175(2): 285-295.
[8] BENSON M J, THOMAS N K, TALWAR S, et al. A novel anticonvulsant mechanism via inhibition of complement receptor C5ar1 in murine epilepsy models[J]. Neurobiology of disease, 2015, 76: 87-97.
| Cell experiment [1]: | |
|
Cell lines |
Mouse neutrophils |
|
Preparation Method |
Mouse neutrophils were isolated from the bone marrow of tibias and femurs from healthy C57BL/6J mice using the Neutrophil Isolation Kit. Neutrophils (5 × 105) were incubated with PMX 53 (10μM) for 1h and then stimulated with recombinant murine C5a (0.1μM) for 3h. Quantification of NET formation capacity in vitro shown as the percentage of NET release, which was assessed by immunofluorescence staining. NETosis was measured using a plate reader assay. |
|
Reaction Conditions |
10μM; 1h |
|
Applications |
NETosis was observed when C5a was added to neutrophil cultures, and this effect was reversed by PMX 53. |
| Animal experiment [2]: | |
|
Animal models |
Sprague-Dawley rats |
|
Preparation Method |
Sprague-Dawley rats received 1mg/kg of PMX 53 via the femoral vein 30min prior to ischemia. Following Basso-Beattie-Bresnahan (BBB) scale assessment, rats were anesthetized and killed. The spinal cord was collected and homogenized, and the expression level of MPO was measured 48h after reperfusion. MPO levels in ischemic spinal cord tissues were measured with a rat MPO ELISA assay kit. MPO activities in spinal cord tissues were calculated by using a standard curve generated with human MPO. |
|
Dosage form |
1mg/kg; i.v. |
|
Applications |
Pre-treatment with PMX 53 significantly attenuated the increase in MPO activity (p<0.05) and reduced the infiltration of inflammatory cells into the ischemic spinal cord. |
|
References: |
|
| Cas No. | 219639-75-5 | SDF | |
| Überlieferungen | 3D53 | ||
| Canonical SMILES | NC(=NCCCC1NC(=O)C(NC(=O)C(CC2CCCCC2)NC(=O)C2N(C(=O)C(CCCNC1=O)NC(=O)C(Cc1ccccc1)NC(=O)C)CCC2)Cc1c[nH]c2c1cccc2)N | ||
| Formula | C47H65N11O7 | M.Wt | 896.1 |
| Löslichkeit | DMSO : 100 mg/mL (111.60 mM; Need ultrasonic); H2O : 2.5 mg/mL (2.79 mM; ultrasonic and warming and heat to 60°C) | Storage | Store at -20°C, protect from light, stored under nitrogen |
| 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. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 1.1159 mL | 5.5797 mL | 11.1595 mL |
| 5 mM | 223.2 μL | 1.1159 mL | 2.2319 mL |
| 10 mM | 111.6 μL | 558 μL | 1.1159 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.50% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 9 reference(s) in Google Scholar.)