| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
Leukotriene C4 synthase (LTC4S).
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|---|---|
| ln Vitro |
TK05 lowers LTC4 production in a dose-dependent manner, with an IC50 value of 318 ± 60 nM in MM6 cells [1].
TK05 inhibits LTC4 synthase with an IC50 of 95 nM. It is selective for LTC4 synthase over microsomal prostaglandin E synthase-1 (mPGES-1), microsomal glutathione S-transferase 2 (GST2), and 5-lipoxygenase (5-LO) at 10 uM. TK05 suppresses LTC4 production in a dose-dependent manner in MM6 cells with an IC50 of 318 +/- 60 nM. |
| ln Vivo |
LTE4 levels are dramatically lowered by TK05 (0.12–6 mg/kg; intraperitoneal injection; once only) [1].
Not specifically reported for this compound. Based on its mechanism, TK05 is expected to reduce cysteinyl leukotriene production in vivo, which would have anti-inflammatory effects in models of asthma and allergic inflammation. |
| Enzyme Assay |
LTC4 synthase enzyme activity assays are performed using microsomal preparations from cells expressing the enzyme. The enzyme is incubated with LTA4 and glutathione in the presence of the compound. LTC4 production is quantified by HPLC or ELISA. IC50 values are determined from concentration-response curves.
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| Cell Assay |
MM6 cells or other leukotriene-producing cells are treated with TK05 and stimulated with calcium ionophore. LTC4 production in the culture supernatant is measured by ELISA or LC-MS. Cell viability is assessed to confirm that the observed effects are not due to cytotoxicity.
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| Animal Protocol |
Animal/Disease Models: Zymosan A-induced peritonitis mouse model [1]
Doses: 0.12 mg/kg; 6 mg/kg Route of Administration: intraperitoneal (ip) injection; Experimental Results: 0.12 mg/kg TK05 Dramatically diminished LTE4 levels, compared with only Compared to mice treated with zymosan A, 6 mg/kg body weight of the compound resulted in almost complete inhibition. Animal models of asthma or allergic inflammation (e.g., ovalbumin-sensitized mice) could be used to assess the in vivo efficacy of TK05. Inflammatory cell infiltration, airway hyperresponsiveness, and LTC4 levels in bronchoalveolar lavage fluid would be measured. |
| ADME/Pharmacokinetics |
Predicted to have moderate oral bioavailability. Likely metabolized by CYP450 enzymes. The compound's lipophilic nature suggests good tissue penetration. Specific pharmacokinetic parameters (half-life, clearance, volume of distribution) have not been reported.
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| Toxicity/Toxicokinetics |
No specific toxicity data reported for TK05. Based on its target selectivity, it is expected to have a favorable safety profile compared to non-selective leukotriene synthesis inhibitors. Standard preclinical toxicity studies would be required for therapeutic development.
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| References | |
| Additional Infomation |
TK05 is a research tool for studying the role of LTC4 synthase and cysteinyl leukotrienes in inflammatory diseases. It has not progressed to clinical trials. The compound is valuable for understanding the therapeutic potential of LTC4 synthase inhibition in asthma, allergic rhinitis, and other inflammatory conditions.
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| Molecular Formula |
C31H25CLN2O5
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|---|---|
| Molecular Weight |
540.993607282639
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| Exact Mass |
540.145
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| CAS # |
1245734-61-5
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| PubChem CID |
53385780
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
6.4
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
39
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| Complexity |
865
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1C=CC(=CC=1)N(C1C=NC(C(C2C=CC(C(C3C=CC(=CC=3)OC)=O)=C(C(=O)O)C=2)=O)=CC=1)CC1CC1
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| InChi Key |
GRDDFJXOEAJYCT-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C31H25ClN2O5/c1-39-25-12-4-20(5-13-25)29(35)26-14-6-21(16-27(26)31(37)38)30(36)28-15-11-24(17-33-28)34(18-19-2-3-19)23-9-7-22(32)8-10-23/h4-17,19H,2-3,18H2,1H3,(H,37,38)
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| Chemical Name |
5-[5-[4-chloro-N-(cyclopropylmethyl)anilino]pyridine-2-carbonyl]-2-(4-methoxybenzoyl)benzoic 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) |
DMSO : ≥ 100 mg/mL (~184.85 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 | 1.8485 mL | 9.2423 mL | 18.4846 mL | |
| 5 mM | 0.3697 mL | 1.8485 mL | 3.6969 mL | |
| 10 mM | 0.1848 mL | 0.9242 mL | 1.8485 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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