| Size | Price | Stock | Qty |
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| 10mg |
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| Targets |
Coagulation Factor XII (FXII) and Plasma Kallikrein (PKal). D-Pro-Phe-Arg-CMK is an irreversible inhibitor of these two serine proteases. The D-amino acid at the N-terminus increases metabolic stability. The chloromethyl ketone (CMK) group is a reactive electrophile that forms a covalent bond with the active site histidine, permanently inactivating the enzyme.
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| ln Vitro |
In vitro, D-Pro-Phe-Arg-Chloromethylketone (PCK) is a potent, irreversible inhibitor of coagulation factor XII and plasma kallikrein. It acts as an active-site titrant, covalently modifying the active site histidine residue. By inhibiting these proteases, it blocks the intrinsic pathway of coagulation and the generation of bradykinin, which is involved in inflammation and pain. Detailed IC50 values are not provided, but PCK is known to be highly potent and selective, and is widely used as a standard inhibitor in coagulation research.
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| ln Vivo |
In vivo, by inhibiting FXII and plasma kallikrein, D-Pro-Phe-Arg-CMK has been shown to play important roles in thrombosis and inflammation. It has been used in animal models to study the contribution of the contact activation system to thrombus formation, angioedema, and sepsis. By irreversibly blocking these proteases, it can prevent thrombosis without increasing bleeding risk, as FXII is not essential for normal hemostasis.
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| Enzyme Assay |
D-Pro-Phe-Arg-CMK can be used as an active-site titrant to determine the concentration of active FXIIa and plasma kallikrein in a solution. A fixed amount of the CMK inhibitor is incubated with a solution containing an unknown concentration of the target enzyme. The residual enzyme activity is measured using a chromogenic substrate (e.g., H-D-Pro-Phe-Arg-pNA). The concentration of active sites is determined by extrapolating the titration curve to zero activity. This is a method for quality control of enzyme preparations.
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| Cell Assay |
For cell-based assays, the compound is used to inhibit FXIIa or plasma kallikrein activity in the conditioned media of cells. It can be added to cell culture media to prevent the activation of the contact system, which might interfere with the study of other pathways. For example, in studies of endothelial cell permeability, PCK can be added to prevent bradykinin generation from plasma kallikrein in supplemented serum. Its cell permeability is not a primary consideration, as its targets are typically in the extracellular environment or on the cell surface.
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| Animal Protocol |
D-Pro-Phe-Arg-CMK has been used in mouse models of thrombosis (e.g., FeCl3-induced carotid artery injury). It can be administered intravenously at doses ranging from 1-10 mg/kg. The time to occlusion is measured as the primary endpoint. It has also been used in models of hereditary angioedema to prevent vascular leakage. The compound's irreversible mechanism results in a sustained pharmacodynamic effect, even after the free drug is cleared from the circulation.
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| ADME/Pharmacokinetics |
The compound is a synthetic peptide with good stability. It has a molecular weight of 450.96 g/mol and a molecular formula of C21H31ClN6O3. It is soluble in DMSO and can be formulated in water (though it may be less stable in aqueous solution). For in vivo use, it is typically formulated in sterile saline or PBS. It should be stored as a lyophilized powder at -20degC to maintain stability. In solution, it should be used promptly and stored at -80degC.
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| Toxicity/Toxicokinetics |
Detailed toxicological data for D-Pro-Phe-Arg-CMK are not provided. As an irreversible inhibitor of FXII and plasma kallikrein, it is expected to have a favorable safety profile, as deficiencies in FXII or plasma kallikrein do not cause a bleeding diathesis. However, the reactive chloromethyl ketone group could potentially react with off-target proteins if not properly dosed. Standard safety precautions for handling research chemicals should be followed. It is not for human use.
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| References | |
| Additional Infomation |
D-Pro-Phe-Arg-Chloromethylketone is also known as PCK, H-D-Pro-Phe-Arg-CMK, and is sometimes simply called "CMK inhibitor." It is used as a standard inhibitor in the study of the contact activation system. It is a valuable tool for dissecting the pathways leading to thrombosis, inflammation, and bradykinin-mediated diseases. The compound is not an FDA-approved drug.
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| Molecular Formula |
C21H31CLN6O3
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|---|---|
| Molecular Weight |
450.96
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| Exact Mass |
450.215
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| CAS # |
88546-74-1
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| PubChem CID |
10456438
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| Appearance |
White to off-white solid powder
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| LogP |
2.323
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
31
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| Complexity |
635
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| Defined Atom Stereocenter Count |
3
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| SMILES |
C1C[C@@H](NC1)C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)N[C@@H](CCCN=C(N)N)C(=O)CCl
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| InChi Key |
HCCRRLVJBLDSLL-BBWFWOEESA-N
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| InChi Code |
InChI=1S/C21H31ClN6O3/c22-13-18(29)15(8-4-11-26-21(23)24)27-20(31)17(12-14-6-2-1-3-7-14)28-19(30)16-9-5-10-25-16/h1-3,6-7,15-17,25H,4-5,8-13H2,(H,27,31)(H,28,30)(H4,23,24,26)/t15-,16+,17-/m0/s1
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| Chemical Name |
(2R)-N-[(2S)-1-[[(3S)-1-chloro-6-(diaminomethylideneamino)-2-oxohexan-3-yl]amino]-1-oxo-3-phenylpropan-2-yl]pyrrolidine-2-carboxamide
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO: 100 mg/mL (221.75 mM)
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| 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 | 2.2175 mL | 11.0875 mL | 22.1749 mL | |
| 5 mM | 0.4435 mL | 2.2175 mL | 4.4350 mL | |
| 10 mM | 0.2217 mL | 1.1087 mL | 2.2175 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.
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