| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 100mg | |||
| Other Sizes |
| Targets |
WKYMVM targets the formyl peptide receptors, specifically FPR1, FPR2 (FPRL1), and FPR3, which are expressed on the surface of immune cells including neutrophils, monocytes, macrophages, and dendritic cells. It acts as a potent agonist with EC50 values of 75 pM for FPR2, 3 nM for FPR3, and approximately 1-10 nM for FPR1. FPRs are G protein-coupled receptors that recognize bacterial formylated peptides and host-derived signals, playing critical roles in chemotaxis, phagocytosis, and the regulation of inflammatory responses. By activating these receptors, WKYMVM triggers downstream signaling cascades involving Gαi proteins, phospholipase C, and intracellular calcium mobilization.
|
|---|---|
| ln Vitro |
WKYMVM exhibits potent agonist activity at FPRs with exceptional potency. The compound shows an EC50 of 75 pM for FPR2, making it one of the most potent FPR agonists described to date. For FPR3, the EC50 is approximately 3 nM, while FPR1 is activated with similar nanomolar potency. In cellular assays, WKYMVM activates several leukocyte effector functions, including chemotaxis, mobilization of complement receptor-3 (CR3), and activation of the NADPH oxidase complex responsible for the respiratory burst. The peptide also induces intracellular calcium flux and promotes the release of pro-inflammatory cytokines and chemokines. These activities make WKYMVM a valuable tool for studying FPR-mediated leukocyte activation and the inflammatory response. In cellular assays, WKYMVM activates multiple leukocyte effector functions through FPR stimulation. The peptide induces robust chemotaxis of neutrophils, monocytes, and other immune cells, directing their migration toward sites of inflammation or infection. It promotes the mobilization of complement receptor-3 (CR3, also known as Mac-1 or CD11b/CD18) to the cell surface, enhancing adhesion and phagocytic capacity. WKYMVM activates the NADPH oxidase complex, generating superoxide and other reactive oxygen species that contribute to microbial killing. The peptide also induces intracellular calcium mobilization, degranulation, and the release of inflammatory mediators. These cellular effects are mediated through FPR-Gαi signaling pathways and can be blocked by pertussis toxin or selective FPR antagonists.
|
| ln Vivo |
In vivo studies with WKYMVM have demonstrated its ability to modulate inflammatory responses in animal models. The peptide induces neutrophil recruitment and activation when administered locally, confirming its in vivo efficacy as an FPR agonist. In models of acute inflammation, WKYMVM enhances leukocyte infiltration and promotes the clearance of bacterial pathogens. Conversely, FPR agonists can also contribute to excessive inflammation and tissue damage in certain contexts. In vivo protocols typically involve administration of WKYMVM via intraperitoneal, intravenous, or subcutaneous injection at doses ranging from 0.1 to 10 mg/kg. Inflammatory markers such as myeloperoxidase activity, cytokine levels, and leukocyte counts are measured. The peptide's short half-life in vivo (due to rapid proteolytic degradation) necessitates careful dosing schedules.
|
| Enzyme Assay |
For FPR binding and activation assays, competition binding experiments are performed using radiolabeled formyl peptides (e.g., [³H]-fMLF or [³H]-WKYMVM) and membrane preparations from cells expressing recombinant FPR subtypes. Membranes are incubated with varying concentrations of unlabeled WKYMVM (0.001 nM to 10 µM) in binding buffer containing 50 mM Tris-HCl, 5 mM MgCl2, 0.5% BSA, and protease inhibitors at 25°C for 60-90 minutes. Bound and free radioligand are separated by filtration through glass fiber filters, and radioactivity is counted by scintillation. For functional assays, GTPγS binding is measured to assess receptor-G protein coupling: membranes are incubated with [³⁵S]-GTPγS (0.1-0.2 nM), varying concentrations of WKYMVM, and GDP in assay buffer at 30°C for 30-60 minutes. Stimulation of [³⁵S]-GTPγS binding indicates receptor activation, and EC50 values are calculated. Calcium mobilization assays in FPR-expressing cells using FLIPR or Fura-2 AM dye are also common.
|
| Cell Assay |
For leukocyte chemotaxis assays, human neutrophils or monocytes are isolated from peripheral blood by density gradient centrifugation (e.g., Ficoll-Paque) followed by dextran sedimentation or magnetic bead separation. Cells are resuspended in RPMI-1640 or HBSS containing 0.1-0.5% BSA at a density of 1-5 × 10⁶ cells/ml. Chemotaxis is assessed using 96-well Boyden chambers or Transwell plates with 3-5 µm pore size membranes. WKYMVM at concentrations ranging from 1 pM to 100 nM is placed in the lower chamber, and cells are added to the upper chamber. After 30-60 minutes of incubation at 37°C, migrated cells are quantified by staining with calcein-AM or crystal violet, followed by fluorescence or absorbance measurement. For NADPH oxidase activation, luminol-enhanced chemiluminescence is used to measure superoxide production. Cells are incubated with luminol and varying concentrations of WKYMVM (0.1 pM to 1 µM), and light emission is recorded.
|
| Animal Protocol |
In vivo models for studying FPR agonists typically involve the murine air pouch model or peritoneal inflammation model. For the air pouch model, sterile air (3-5 ml) is injected subcutaneously into the dorsum of mice to form an air pouch, which is allowed to mature for 3-4 days. WKYMVM (0.1-10 µg per pouch) or vehicle control is injected into the pouch, and after 2-6 hours, the pouch exudate is collected. Leukocyte infiltration (total cell count and differential), myeloperoxidase activity, and cytokine levels (e.g., TNF-α, IL-1β, IL-6) are measured. For the peritoneal inflammation model, WKYMVM (0.1-10 mg/kg) is administered intraperitoneally, and peritoneal lavage is performed after 2-4 hours to collect infiltrating leukocytes. Blood samples may be collected for assessing systemic inflammatory markers. In models of bacterial infection, WKYMVM is administered prophylactically or therapeutically, and bacterial burden is measured by colony counting from infected tissues.
|
| ADME/Pharmacokinetics |
Pharmacokinetic data for WKYMVM are limited due to its nature as a peptide and its primary use as a research tool. As a hexapeptide, WKYMVM is susceptible to rapid proteolytic degradation by serum and tissue peptidases, resulting in a short plasma half-life (likely minutes). The peptide is not expected to have significant oral bioavailability and is typically administered by injection. Its metabolism involves cleavage by endopeptidases and exopeptidases, producing smaller peptide fragments and free amino acids. Tissue distribution is limited due to its hydrophilic nature and high molecular weight. These pharmacokinetic limitations are typical of peptide-based research reagents and must be considered when designing in vivo experiments. No extensive ADME studies have been reported for WKYMVM.
|
| Toxicity/Toxicokinetics |
Toxicological data for WKYMVM are limited, as the peptide is intended for research use only and has not been developed as a therapeutic agent. In cellular assays, WKYMVM shows activity at picomolar to nanomolar concentrations and is generally well-tolerated at these levels. At higher concentrations (microgram levels), the peptide may induce excessive inflammatory responses due to potent FPR activation, potentially leading to tissue damage. In vivo, WKYMVM can cause leukocyte infiltration and inflammation at the injection site, which is consistent with its mechanism of action as an FPR agonist. No acute toxicity, organ-specific toxicity, or mutagenicity data have been reported. Standard laboratory safety precautions should be followed when handling WKYMVM, including the use of gloves and eye protection.
|
| References |
|
| Additional Infomation |
WKYMVM is a synthetic hexapeptide widely used as a research tool for studying formyl peptide receptor biology. The peptide is named by its single-letter amino acid sequence: W (tryptophan), K (lysine), Y (tyrosine), M (methionine), V (valine), M (methionine). Unlike bacterial formylated peptides (e.g., fMLF), WKYMVM is non-formylated yet exhibits higher potency and broader receptor subtype selectivity, making it a superior tool for FPR research. The peptide activates FPR1, FPR2, and FPR3, with exceptional potency at FPR2 (EC50 = 75 pM). WKYMVM is widely used in immunology to investigate leukocyte chemotaxis, phagocytosis, respiratory burst, and inflammatory signaling. It has not entered clinical trials and is strictly for research use only. WKYMVM is typically supplied as the TFA salt for improved solubility and stability.
|
| Molecular Formula |
C41H61N9O7S2
|
|---|---|
| Molecular Weight |
856.109140000001
|
| Exact Mass |
856.398
|
| CAS # |
187986-17-0
|
| Related CAS # |
WKYMVM TFA;1313730-09-4
|
| PubChem CID |
457933
|
| Appearance |
White to off-white solid powder
|
| LogP |
5.14
|
| Hydrogen Bond Donor Count |
10
|
| Hydrogen Bond Acceptor Count |
11
|
| Rotatable Bond Count |
26
|
| Heavy Atom Count |
59
|
| Complexity |
1360
|
| Defined Atom Stereocenter Count |
6
|
| SMILES |
CC(C)[C@@H](C(=O)N[C@H](CCSC)C(=O)N)NC(=O)[C@H](CCSC)NC(=O)[C@H](CC1=CC=C(C=C1)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC2=CNC3=CC=CC=C32)N
|
| InChi Key |
FMBGOORJEKQQLG-JUZZZACGSA-N
|
| InChi Code |
InChI=1S/C41H61N9O7S2/c1-24(2)35(41(57)46-31(36(44)52)16-19-58-3)50-39(55)33(17-20-59-4)48-40(56)34(21-25-12-14-27(51)15-13-25)49-38(54)32(11-7-8-18-42)47-37(53)29(43)22-26-23-45-30-10-6-5-9-28(26)30/h5-6,9-10,12-15,23-24,29,31-35,45,51H,7-8,11,16-22,42-43H2,1-4H3,(H2,44,52)(H,46,57)(H,47,53)(H,48,56)(H,49,54)(H,50,55)/t29-,31+,32-,33-,34-,35-/m0/s1
|
| Chemical Name |
(2S)-6-amino-2-[[(2S)-2-amino-3-(1H-indol-3-yl)propanoyl]amino]-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2R)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]hexanamide
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
H2O : ~12.5 mg/mL (~14.60 mM)
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.1681 mL | 5.8404 mL | 11.6807 mL | |
| 5 mM | 0.2336 mL | 1.1681 mL | 2.3361 mL | |
| 10 mM | 0.1168 mL | 0.5840 mL | 1.1681 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
