| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
PKSI-527 targets plasma kallikrein, a serine protease that plays a key role in the kallikrein-kinin system. Plasma kallikrein is involved in the generation of bradykinin, a potent vasoactive peptide that mediates inflammation, pain, and vascular permeability. By selectively inhibiting plasma kallikrein, PKSI-527 modulates the kallikrein-kinin system and reduces inflammatory responses. The compound's high selectivity makes it a valuable tool for studying the specific role of plasma kallikrein in various physiological and pathological processes.
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| ln Vitro |
In vitro, PKSI-527 demonstrates potent and selective inhibition of plasma kallikrein activity. The compound shows high selectivity for plasma kallikrein over other serine proteases, making it a specific tool for studying kallikrein-mediated pathways. PKSI-527 inhibits kallikrein activity in biochemical assays using purified enzyme and synthetic substrates. The compound's inhibitory activity is concentration-dependent, with effective inhibition achieved at nanomolar to micromolar concentrations depending on the assay conditions.
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| ln Vivo |
In vivo, PKSI-527 has been evaluated in animal models of arthritis. The compound suppresses collagen-induced arthritis (CIA) by modifying the kallikrein-kinin system. This demonstrates the compound's efficacy in modulating inflammatory responses in vivo. PKSI-527's ability to suppress arthritis in preclinical models supports its utility as a research tool for studying inflammatory diseases and the kallikrein-kinin system.
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| Enzyme Assay |
The in vitro enzyme inhibition assay for PKSI-527 typically involves measuring plasma kallikrein activity using a chromogenic or fluorogenic substrate. Purified human plasma kallikrein is incubated with varying concentrations of PKSI-527 (0.001-100 µM) in assay buffer at 37°C for 10-30 minutes. The reaction is initiated by adding the substrate, and absorbance or fluorescence is measured. IC50 values are calculated from dose-response curves. Selectivity is assessed by testing against other serine proteases.
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| Cell Assay |
For in vitro cell-based assays, cells expressing kallikrein or involved in inflammatory responses are cultured and treated with PKSI-527 at concentrations ranging from 0.1-100 µM for 1-24 hours. Kallikrein activity is measured in cell lysates or conditioned media using activity assays. Bradykinin production is measured by ELISA. Inflammatory cytokine levels are assessed by qPCR or ELISA. Cell viability is assessed using MTT or CCK-8 assays.
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| Animal Protocol |
In vivo animal studies for PKSI-527 are conducted using models of collagen-induced arthritis (CIA) in mice or rats. PKSI-527 is administered via oral gavage, intraperitoneal injection, or intravenous injection at doses ranging from 1-50 mg/kg daily for 1-4 weeks. Arthritis severity is assessed by clinical scoring, paw swelling measurements, and histopathological analysis of joints. Kallikrein activity and bradykinin levels are measured in plasma and joint tissues.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of PKSI-527 have been characterized to some extent. Molecular weight is 473.99 and molecular formula is C₂₅H₃₂ClN₃O₄. Purity is ≥95%. CAS number is 128837-71-8. Detailed pharmacokinetic parameters such as bioavailability, half-life, and protein binding have been reported in the literature. The compound is soluble in appropriate solvents and should be stored under recommended conditions.
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| Toxicity/Toxicokinetics |
Toxicology data for PKSI-527 are limited. As a research compound, it has not been fully evaluated for safety. The compound's mechanism of plasma kallikrein inhibition suggests potential effects on the kallikrein-kinin system and inflammatory responses, which would require careful safety assessment. Standard toxicological endpoints including body weight, organ weights, clinical chemistry, and histopathology should be evaluated. The compound is intended for research use only.
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| References | |
| Additional Infomation |
PKSI-527 is a highly selective plasma kallikrein inhibitor used as a research tool for studying the kallikrein-kinin system, inflammation, and arthritis. The compound suppresses collagen-induced arthritis in preclinical models and is also used for affinity purification of kallikrein. PKSI-527 is a valuable tool for investigating the role of plasma kallikrein in inflammatory diseases and for developing therapeutic strategies targeting the kallikrein-kinin system. It is intended for research use only and is not approved for clinical applications.
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| Molecular Formula |
C25H32CLN3O4
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|---|---|
| Molecular Weight |
473.99
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| Exact Mass |
473.208
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| CAS # |
128837-71-8
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| PubChem CID |
3035562
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| Appearance |
Off-white to light yellow solid powder
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| Boiling Point |
763.1ºC at 760mmHg
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| Flash Point |
415.3ºC
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| Vapour Pressure |
1.74E-24mmHg at 25°C
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| LogP |
5.16
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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 |
9
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| Heavy Atom Count |
33
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| Complexity |
619
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C1CC(CCC1CN)C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)NC3=CC=C(C=C3)CC(=O)O.Cl
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| InChi Key |
NAXNMKUKSBHHMP-QCXPCDNBSA-N
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| InChi Code |
InChI=1S/C25H31N3O4.ClH/c26-16-19-6-10-20(11-7-19)24(31)28-22(14-17-4-2-1-3-5-17)25(32)27-21-12-8-18(9-13-21)15-23(29)30;/h1-5,8-9,12-13,19-20,22H,6-7,10-11,14-16,26H2,(H,27,32)(H,28,31)(H,29,30);1H/t19?,20?,22-;/m0./s1
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| Chemical Name |
2-[4-[[(2S)-2-[[4-(aminomethyl)cyclohexanecarbonyl]amino]-3-phenylpropanoyl]amino]phenyl]acetic acid;hydrochloride
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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 |
| 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 (210.97 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 | 2.1097 mL | 10.5487 mL | 21.0975 mL | |
| 5 mM | 0.4219 mL | 2.1097 mL | 4.2195 mL | |
| 10 mM | 0.2110 mL | 1.0549 mL | 2.1097 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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