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| Targets |
PSI-697 targets P-selectin, a cell adhesion molecule (also known as CD62P) that is expressed on the surface of activated platelets and endothelial cells. P-selectin mediates the rolling and adhesion of leukocytes (white blood cells) to the vascular endothelium, a critical early step in the inflammatory response and thrombus formation. By acting as a small-molecule antagonist, PSI-697 binds to P-selectin and blocks its interaction with its ligand, P-selectin glycoprotein ligand-1 (PSGL-1). This inhibition prevents leukocyte adhesion and recruitment to sites of inflammation and thrombosis, thereby reducing vascular injury and thrombus formation. Importantly, PSI-697 achieves this antithrombotic effect without inducing anticoagulation, offering a potential advantage over traditional anticoagulants.
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| ln Vitro |
It was determined that PSI-697 would block 50% of binding at 125 μM [1].
In vitro, PSI-697 functions as a P-selectin antagonist, blocking the interaction between P-selectin and its ligand PSGL-1. This prevents the adhesion of leukocytes to activated platelets and endothelial cells. Detailed in vitro activity data, including specific IC50 values for inhibition of P-selectin binding, are not extensively reported in the available literature. The compound's activity is confirmed through cell adhesion assays where the inhibition of leukocyte rolling or adhesion is measured. |
| ln Vivo |
In comparison to vascular platforms, PSI-697 (0-50 mg/kg; channel) dramatically lowers rolling leukocyte counts by 39% [1]. In a vascular venous thrombosis model, PSI-697 (100 mg/kg; Channel) decreases thrombus weight by 18% in comparison to arterial material without lengthening the thrombosis period [1]. In a baboon model of vasculogenesis, PSI-697 (30 mg/kg; Manhattan daily; 6 days) reduces blood vessels and increases thrombolysis. In a model of wall damage, PSI-697 (30 mg/kg; ig; daily) decreases venous thrombosis and venous stenosis.
In vivo, PSI-697 has demonstrated efficacy in reducing vein wall injury in a rat stenosis model of venous thrombosis. In this model, oral administration of PSI-697 at 30 mg/kg daily significantly decreased the intimal thickness score compared with vehicle control. These findings confirm its in vivo efficacy in reducing vascular injury and thrombosis. The compound's oral bioavailability and lack of anticoagulation make it a promising candidate for further development in cardiovascular diseases. |
| Enzyme Assay |
Non-cell-based assays for PSI-697 include P-selectin binding assays using purified P-selectin protein or recombinant P-selectin. The compound is incubated with P-selectin and a labeled ligand (e.g., PSGL-1 or a monoclonal antibody) at varying concentrations. Binding affinity is determined by measuring the displacement of the labeled ligand using techniques such as ELISA, fluorescence polarization, or surface plasmon resonance. IC50 values for inhibition of binding are determined.
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| Cell Assay |
Cellular assays for PSI-697 utilize cell adhesion assays to assess its ability to inhibit P-selectin-mediated adhesion. Endothelial cells or platelets expressing P-selectin are cultured, and leukocytes (or leukocyte cell lines) are added in the presence of the compound at various concentrations. The number of adherent cells is quantified after washing. Inhibition of adhesion is calculated as a percentage of control. Flow cytometry can also be used to measure the binding of P-selectin to its ligand on leukocytes.
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| Animal Protocol |
Animal/Disease Models: 4-5 weeks male SD (SD (Sprague-Dawley)) rat (50-100 g)[1]
Doses: 0 mg/kg, 30 mg/kg, 50 mg/kg Route of Administration: Oral Experimental Results: The number of rolling leukocytes was diminished by 39% at the oral dose of 50 mg/kg compared to vehicle control. In vivo animal models for PSI-697 include the rat stenosis model of venous thrombosis. In this model, venous stenosis is induced, and the compound is administered orally at doses such as 30 mg/kg daily. After a specified period, vein wall injury and thrombus formation are assessed by histological examination, with intimal thickness and other parameters measured. Other models of inflammation and thrombosis, such as acute pancreatitis models, may also be used. Detailed protocols are reported in the literature. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of PSI-697 include a molecular weight of 367.83 g/mol and molecular formula C21H18ClNO3. CAS number is 851546-61-7. The compound is orally active. Purity is 98.24%. The compound is a small molecule P-selectin antagonist. Detailed PK parameters such as half-life and bioavailability are not extensively reported, but oral administration is used in vivo.
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| Toxicity/Toxicokinetics |
Detailed toxicological data for PSI-697 are not extensively reported in the available literature. As a research compound, its safety profile would need to be established through standard preclinical toxicity assessments. The compound is supplied for research use only. Given its mechanism of P-selectin inhibition, potential effects on immune function and bleeding risk would be key safety considerations. Importantly, PSI-697 achieves its antithrombotic effect without anticoagulation, suggesting a favorable safety profile.
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| References |
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| Additional Infomation |
PSI-697 has been used in trials investigating the treatment of scleritis.
PSI-697 is a novel small-molecule antagonist of P-selectin. It has CAS number 851546-61-7. It is a quinoline derivative with the molecular formula C21H18ClNO3 and a molecular weight of 367.83 g/mol. It inhibits P-selectin-mediated cell adhesion and has shown efficacy in reducing vein wall injury in a rat model of venous thrombosis. It is being studied for potential therapeutic applications in cardiovascular diseases and acute pancreatitis. It is for research use only.** |
| Molecular Formula |
C21H18CLNO3
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| Molecular Weight |
367.829
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| Exact Mass |
367.098
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| CAS # |
851546-61-7
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| PubChem CID |
12004316
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
4.761
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
26
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| Complexity |
508
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
DIEPFYNZGUUVHD-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H18ClNO3/c22-14-8-5-12(6-9-14)11-17-20(24)18(21(25)26)16-10-7-13-3-1-2-4-15(13)19(16)23-17/h5-10,24H,1-4,11H2,(H,25,26)
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| Chemical Name |
2-[(4-chlorophenyl)methyl]-3-hydroxy-7,8,9,10-tetrahydrobenzo[h]quinoline-4-carboxylic acid
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| Synonyms |
PSI 697 PSI697 PSI-697
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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 : ≥ 45.8 mg/mL (~124.51 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 | 2.7186 mL | 13.5932 mL | 27.1865 mL | |
| 5 mM | 0.5437 mL | 2.7186 mL | 5.4373 mL | |
| 10 mM | 0.2719 mL | 1.3593 mL | 2.7186 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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