| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 100mg | |||
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| Targets |
TCV-309 chloride targets the platelet activating factor (PAF) receptor, a G protein-coupled receptor that mediates the biological effects of PAF, a potent phospholipid mediator of inflammation, thrombosis, and anaphylaxis. PAF is involved in platelet aggregation, leukocyte activation, vascular permeability, and hypotension. By antagonizing the PAF receptor, TCV-309 chloride blocks PAF-induced signaling, including platelet aggregation, inflammation, and vascular effects. The compound specifically inhibits PAF-induced aggregation of rabbit and human platelets with IC₅0 values of 33 nM and 58 nM, respectively. TCV-309 chloride is also reported as a thromboxane A2 (TXA2) receptor antagonist.
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| ln Vitro |
In vitro, TCV-309 chloride potently inhibits PAF-induced platelet aggregation and PAF receptor binding. The compound specifically inhibits PAF-induced aggregation of rabbit and human platelets with IC₅0 values of 33 nM and 58 nM, respectively. It also inhibits [3H]PAF binding to rabbit platelet microsomes with an IC₅0 of 27 nM. In cellular assays, TCV-309 chloride blocks PAF-induced calcium mobilization, phospholipase C activation, and inflammatory cytokine production. The compound shows high selectivity for the PAF receptor over other lipid mediators and receptors.
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| ln Vivo |
TCV-309 had ED50 values of 2.7, 6.4, and 1.7 μg/kg (iv) in rats, which indicates its specific inhibition of PAF-induced hypotension, hemoconcentration, and mortality. With ED50 values of 2.1 and 2.6 μg/kg(iv), respectively, TCV-309 most effectively shields mice from anaphylactic shock and PAF-induced mortality [1]. With ED50 values of 3.3 and 1.2 μg/kg (iv), respectively, TCV-309 chloride may also correct endotoxin- and PAF-induced hypotension in rats [1].
In vivo, TCV-309 chloride effectively protects mice against PAF- and anaphylaxis-induced death with ED₅0 values of 2.1 and 2.6 microg/kg (i.v.), respectively. The compound reverses PAF-induced hypotension and endotoxin-induced hypotension in rats. It also inhibits PAF-induced hemoconcentration and death with ED₅0 values of 6.4 and 1.7 microg/kg (i.v.), respectively. These protective effects demonstrate the compound's potent in vivo PAF antagonism and its potential for treating PAF-mediated inflammatory and vascular disorders. The compound is used in research to study PAF-mediated signaling and inflammatory pathways. |
| Enzyme Assay |
In vitro receptor binding assays for TCV-309 chloride are performed using membrane preparations from rabbit platelets or cells expressing recombinant human PAF receptors. Radiolabeled ligand [3H]PAF is used. Membranes are incubated with varying concentrations of TCV-309 chloride in assay buffer at room temperature for 60-90 minutes. Bound and free radioligands are separated by rapid filtration through glass fiber filters. Filter-bound radioactivity is quantified by liquid scintillation counting. IC₅0 values for inhibition of PAF binding are determined from dose-response curves. Functional assays measure PAF-induced platelet aggregation in platelet-rich plasma using an aggregometer. IC₅0 values for inhibition of aggregation are calculated.
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| Cell Assay |
Cellular assays for TCV-309 chloride are performed using platelets, leukocytes, or cell lines expressing PAF receptors. Platelets are isolated from whole blood by centrifugation and resuspended in buffer. PAF-induced platelet aggregation is measured using a platelet aggregometer in the presence of serial dilutions of TCV-309 chloride (0.001-10 microM). For calcium mobilization assays, cells are loaded with Fluo-4 and treated with TCV-309 chloride prior to PAF stimulation. Intracellular calcium is measured by fluorescence spectroscopy. Inflammatory cytokine production (TNF-alpha, IL-6) is measured by ELISA in PAF-stimulated macrophages or monocytes treated with the compound.
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| Animal Protocol |
In vivo animal studies for TCV-309 chloride are conducted in mouse and rat models of PAF-induced shock and anaphylaxis. In mouse models, TCV-309 chloride is administered intravenously at doses of 0.1-10 microg/kg prior to PAF challenge or antigen-induced anaphylaxis. Survival is monitored, and ED₅0 values for protection against death are calculated. In rat models, the compound is administered intravenously, and blood pressure is monitored by arterial catheter. PAF-induced hypotension and endotoxin-induced hypotension are assessed. Hemoconcentration is measured by hematocrit. Pharmacokinetic parameters are determined from plasma samples.
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| ADME/Pharmacokinetics |
TCV-309 chloride (CAS#: 121494-09-5) has molecular formula C30H34BrClN4O4 and molecular weight 629.97. The compound is a potent and specific platelet activating factor (PAF) receptor antagonist. It specifically inhibits PAF-induced aggregation of rabbit and human platelets and [3H]PAF binding to rabbit platelet microsomes with IC₅0 values of 33 nM, 58 nM, and 27 nM, respectively. The compound protects mice against PAF- and anaphylaxis-induced death with ED₅0 values of 2.1 and 2.6 microg/kg (i.v.). Purity is typically ≥95%. Storage should be at -20degC. For research use only.
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| References |
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| Additional Infomation |
TCV-309 chloride (CAS#: 121494-09-5) is a potent and specific platelet activating factor (PAF) receptor antagonist. PAF is a potent phospholipid mediator of inflammation, thrombosis, and anaphylaxis, acting through the PAF receptor to induce platelet aggregation, leukocyte activation, vascular permeability, and hypotension. TCV-309 chloride specifically inhibits PAF-induced aggregation of rabbit and human platelets and [3H]PAF binding with IC₅0 values of 33 nM, 58 nM, and 27 nM, respectively. The compound protects mice against PAF- and anaphylaxis-induced death and reverses PAF- and endotoxin-induced hypotension in rats. As of the current date, TCV-309 chloride remains a preclinical research compound and is not approved for clinical use.
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| Molecular Formula |
C30H34BRCLN4O4
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| Molecular Weight |
629.972365856171
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| Exact Mass |
628.145
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| CAS # |
121494-09-5
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| PubChem CID |
15037614
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| Appearance |
Light yellow to yellow solid powder
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
40
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| Complexity |
808
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| Defined Atom Stereocenter Count |
0
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| SMILES |
BrC1C=C(C=[N+](C=1)CCC)C(N(C1C=CC=CC=1)CCC(NCCOC(N1CC2C=CC=CC=2CC1)=O)=O)=O.[Cl-]
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| InChi Key |
HBWMSZWQSYEBPL-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C30H33BrN4O4.ClH/c1-2-15-33-20-25(19-26(31)22-33)29(37)35(27-10-4-3-5-11-27)17-13-28(36)32-14-18-39-30(38)34-16-12-23-8-6-7-9-24(23)21-34;/h3-11,19-20,22H,2,12-18,21H2,1H3;1H
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| Chemical Name |
2-[3-(N-(5-bromo-1-propylpyridin-1-ium-3-carbonyl)anilino)propanoylamino]ethyl 3,4-dihydro-1H-isoquinoline-2-carboxylate;chloride
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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, avoid exposure to moisture. |
| 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 : ~6.3 mg/mL (~10.00 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 | 1.5874 mL | 7.9369 mL | 15.8738 mL | |
| 5 mM | 0.3175 mL | 1.5874 mL | 3.1748 mL | |
| 10 mM | 0.1587 mL | 0.7937 mL | 1.5874 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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