| Size | Price | Stock | Qty |
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| 1mg |
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| 100mg | |||
| Other Sizes |
| Targets |
The primary target of CGS 15435 is thromboxane A2 synthase (TxA2 synthase), the enzyme responsible for the conversion of prostaglandin H2 (PGH2) to thromboxane A2 (TxA2). CGS 15435 is a potent inhibitor of this enzyme, with an IC50 of 1 nM. Its selectivity for TxA2 synthase is remarkable; it is 100,000-fold more selective for TxA2 synthase than for cyclooxygenase, prostacyclin (PGI2) synthase, and lipoxygenase. TxA2 is a potent vasoconstrictor and inducer of platelet aggregation, playing a critical role in hemostasis and thrombosis. By inhibiting its synthesis, CGS 15435 can reduce platelet aggregation and vasoconstriction, making it a potential therapeutic agent for cardiovascular diseases.
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| ln Vitro |
CGS 15435 is a highly specific inhibitor of Tx synthase. CGS 15435 is only a weak inhibitor of product formation of PGE2 (cyclooxygenase, IC50=1200 μM), prostacyclin (PGI2 synthase, IC50=90 μM) or 5-lipoxygenase (IC50=60 μM). Impact [1].
In vitro, CGS 15435 is a highly specific inhibitor of Tx synthase. It exhibits only weak inhibitory activity against other enzymes in the arachidonic acid pathway. For example, it inhibits cyclooxygenase (PGE2 formation) with an IC50 of 1200 μM, PGI2 synthase with an IC50 of 90 μM, and 5-lipoxygenase with an IC50 of 60 μM. This high degree of selectivity underscores its utility as a specific tool for studying the role of TxA2 without the confounding effects of inhibiting other pathways. The compound's in vitro activity can be assessed by measuring the production of TxB2, the stable metabolite of TxA2, in cell cultures or platelet-rich plasma treated with the compound. |
| ln Vivo |
The increase in TxB2 plasma levels is inhibited even 24 hours after CGS 15435 injection, indicating a prolonged duration of action for CGS 15435. TxB2 formation was substantially suppressed by CGS 15435 at 4, 6, 12, and 24 hours following injection. In rats that survived, administration of CGS 15435 0.25 or 24 hours prior to arachidonic acid (AA) did not enhance TxB2 (4/4 and 5/6, respectively). Compared to the AA or Dazoxiben (2 hour pretreatment) groups, the final TxB2 levels in the CGS15435A (0.25 and 24 hours pretreatment) group were considerably lower [1].
In vivo, CGS 15435 demonstrates a prolonged duration of action. Studies in rats have shown that a single injection of CGS 15435 inhibits the increase in plasma TxB2 levels for up to 24 hours. TxB2 formation was substantially suppressed at 4, 6, 12, and 24 hours following injection. In rats challenged with arachidonic acid (AA), a precursor of TxA2, administration of CGS 15435 0.25 or 24 hours prior to AA injection effectively suppressed TxB2 formation. This extended duration of action is a key feature of CGS 15435, making it a valuable tool for in vivo studies of thromboxane-mediated processes. The compound's in vivo effects are likely related to its ability to shift the balance of arachidonic acid metabolites away from pro-thrombotic and vasoconstrictive TxA2 towards other metabolites. |
| Enzyme Assay |
For in vitro enzyme assays, the activity of CGS 15435 is typically assessed using purified thromboxane synthase or enzyme preparations from platelets. The enzyme is incubated with its substrate, prostaglandin H2 (PGH2), in the presence of varying concentrations of the inhibitor. The production of TxB2, the stable metabolite of TxA2, is then measured using Enzyme-Linked Immunosorbent Assay (ELISA) or radioimmunoassay (RIA). The IC50, the concentration required to inhibit 50% of enzyme activity, is determined from dose-response curves. For selectivity profiling, similar assays are performed with cyclooxygenase, PGI2 synthase, and lipoxygenase.
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| Cell Assay |
For in vitro cell-based assays, the activity of CGS 15435 can be evaluated using platelet-rich plasma (PRP) or whole blood. Platelets are stimulated with agonists such as arachidonic acid, collagen, or thrombin to induce TxA2 synthesis and aggregation. The compound is added to the PRP or blood sample prior to stimulation, and the production of TxB2 is measured in the supernatant. Platelet aggregation can also be monitored using aggregometry. The compound's effects on other cell types, such as endothelial cells or macrophages, can be studied by measuring the production of TxB2 and other eicosanoids after stimulation with inflammatory stimuli like lipopolysaccharide (LPS).
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| Animal Protocol |
For in vivo animal studies, CGS 15435 is typically administered via intravenous or intraperitoneal injection in rodent models. The compound's pharmacokinetics and pharmacodynamics have been studied in rats. In arachidonic acid-induced mortality models, the compound's protective effects can be evaluated by assessing survival rates. In models of thrombosis, the compound's ability to reduce platelet aggregation and thrombus formation can be assessed. In inflammatory models, the compound's effects on TxA2-mediated inflammation, such as carrageenan-induced paw edema, can be evaluated. Blood samples are collected at various time points to measure TxB2 levels and confirm target engagement.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of CGS 15435: The compound has a molecular weight of 356.85 and a LogP of 4.4, indicating moderate lipophilicity. It is typically formulated for injection in in vivo studies. The compound's extended duration of action, as demonstrated by sustained inhibition of TxB2 formation for up to 24 hours in rats, suggests it has a long half-life or is tightly bound to its target. Detailed pharmacokinetic parameters such as clearance, volume of distribution, and oral bioavailability are not publicly available. CGS 15435 is available in 1 mg and 100 mg sizes for research.
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| Toxicity/Toxicokinetics |
Specific toxicity data for CGS 15435 are limited in publicly available literature. As a potent inhibitor of thromboxane synthase, its primary pharmacological effect—inhibition of platelet aggregation—could be a safety concern in vivo, potentially increasing bleeding risk. However, the compound is used as a research tool and is not intended for human therapeutic use. Standard laboratory safety precautions should be observed when handling the compound.
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| References |
[1]. Olson RW, et al. CGS 15435A, a thromboxane synthetase inhibitor with an extended duration of action: a comparison with dazoxiben. Eur J Pharmacol. 1987 Jan 20;133(3):265-73
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| Additional Infomation |
CGS 15435 is a research compound with no clinical trial or regulatory approval status. It is a potent and highly selective thromboxane synthase inhibitor used as a pharmacological tool to study the role of the thromboxane pathway. It is commercially available from chemical suppliers for research purposes only. The compound is particularly useful for investigating the role of TxA2 in cardiovascular diseases, thrombosis, and inflammation. Its high selectivity and prolonged duration of action make it a valuable alternative to other thromboxane synthase inhibitors like dazoxiben.
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| Molecular Formula |
C20H21N2O2CL
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|---|---|
| Molecular Weight |
356.846
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| Exact Mass |
356.129
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| CAS # |
95853-92-2
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| PubChem CID |
129519
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
4.4
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
25
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| Complexity |
447
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CN1C2=C(C=C(C=C2)Cl)C(=C1C3=CN=CC=C3)CCCCCC(=O)O
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| InChi Key |
BYQANTGKEVLUKZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H21ClN2O2/c1-23-18-10-9-15(21)12-17(18)16(7-3-2-4-8-19(24)25)20(23)14-6-5-11-22-13-14/h5-6,9-13H,2-4,7-8H2,1H3,(H,24,25)
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| Chemical Name |
6-(5-chloro-1-methyl-2-pyridin-3-ylindol-3-yl)hexanoic acid
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 2.8023 mL | 14.0115 mL | 28.0230 mL | |
| 5 mM | 0.5605 mL | 2.8023 mL | 5.6046 mL | |
| 10 mM | 0.2802 mL | 1.4011 mL | 2.8023 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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