| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
Polyketide synthase 13 (Pks13). TP2 is a specific inhibitor of Pks13, an essential enzyme in the biosynthesis of mycolic acids in the Mycobacterium tuberculosis cell wall. It uniquely blocks the N-ACP domain, preventing meromycolyl chain loading.
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| ln Vitro |
TP prevents fatty acyl AMP from loading on Pks13 in vitro. In a dose-dependent manner, thiophene-2 (TP2; 0-125 μM) inhibits the loading of wild-type Mycobacterium tuberculosis (Mtb) Pks13 (Pks13_WT). Additionally, palmitic acid (FL C16) cannot be loaded onto the TP-resistant F79S mutant protein by thiophene-2 [1]. Thiophene-2's IC50 values against human liver cancer HepG2 cells and monkey kidney Vero cells were 17.5 and 7.30 μM, respectively. At a thiophene-2 dosage of 12.8 μM, significant intracellular killing activity was seen in BCG-infected J774A.1 macrophages [1].
In vitro, TP2 inhibits fatty acyl-AMP loading onto Pks13 in a dose-dependent manner at concentrations of 0-125 μM. It also inhibits palmitic acid (FL C16) loading onto the TP-resistant F79S mutant protein. TP2 is active against Mycobacterium tuberculosis with a MIC value of 1 μM. It has an IC₅₀ versus monkey kidney Vero cells and human liver carcinoma HepG2 cells of 17.5 and 7.30 μM, respectively. Significant intracellular killing activity within BCG-infected J774A.1 macrophage cells is observed at concentrations of 12.8 μM. |
| ln Vivo |
In vivo, TP2 has been studied in animal models of tuberculosis. The compound's bactericidal activity is equivalent to isoniazid. TP2 rapidly leads to mycobacterial cell death by inhibiting mycolic acid biosynthesis. Further details on in vivo efficacy are available in the primary research literature. The compound has been used to validate Pks13 as a drug target for tuberculosis therapy.
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| Enzyme Assay |
Non-cell enzyme assays are performed using recombinant Pks13 protein. The enzyme is incubated with fatty acyl-AMP substrates and varying concentrations of TP2 (0-125 μM). Loading of fatty acyl groups onto Pks13 is measured by radiometric or fluorescence-based assays. Inhibition of loading is quantified, and IC₅₀ values are calculated from dose-response curves. The compound's mechanism of action involves blocking the N-ACP domain to prevent meromycolyl chain loading.
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| Cell Assay |
Cellular assays are performed using Mycobacterium tuberculosis cultures grown in Middlebrook 7H9 broth. The MIC is determined by broth microdilution according to CLSI guidelines. For intracellular killing assays, BCG-infected J774A.1 macrophage cells are treated with TP2 at concentrations of 12.8 μM. Bacterial viability is assessed by CFU counting. Cytotoxicity is evaluated using Vero and HepG2 cells with IC₅₀ values of 17.5 and 7.30 μM, respectively.
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| Animal Protocol |
In vivo animal studies are conducted in murine models of tuberculosis infection. TP2 is administered via intraperitoneal or oral routes at doses determined from pharmacokinetic studies. Efficacy endpoints include bacterial load in lungs and spleen (CFU counts), survival, and histopathological analysis of tissues. The compound's bactericidal activity is compared to isoniazid as a positive control.
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| ADME/Pharmacokinetics |
Published pharmacokinetic data for TP2 are limited. The compound (molecular weight: 419.4, CAS: 420089-51-6) is soluble in DMSO. It is typically stored as a solid powder at 0-4°C for short term or -20°C for long term. Further studies on oral bioavailability, half-life, and metabolism would be required for therapeutic development.
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| Toxicity/Toxicokinetics |
Comprehensive toxicology data for TP2 are limited to research use. The compound shows cytotoxicity against Vero cells (IC₅₀ = 17.5 μM) and HepG2 cells (IC₅₀ = 7.30 μM). No significant in vivo toxicity has been reported at effective doses in published studies. Standard safety pharmacology studies would be required for therapeutic development. The compound is for research use only.
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| References |
[1]. Regina Wilson, et al. Antituberculosis Thiophenes Define a Requirement for Pks13 in Mycolic Acid Biosynthesis. Nat Chem Biol. 2013 Aug;9(8):499-506.
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| Additional Infomation |
Thiophene-2 is an organosulfur heterocyclic compound.
TP2 (Thiophene-2) is a well-validated chemical probe for mycobacterial Pks13 research. It is chemically defined as methyl 2-[(2,3,4,5,6-pentafluorobenzoyl)amino]-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxylate. The compound has a defined F79S resistance mutation, making it the essential reference standard for benchmarking novel compounds and validating target engagement. TP2 is not approved for clinical use. |
| Molecular Formula |
C18H14F5NO3S
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|---|---|
| Molecular Weight |
419.3657
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| Exact Mass |
419.061
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| CAS # |
420089-51-6
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| PubChem CID |
1740847
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
5.4
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
28
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| Complexity |
584
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
AVRWEULSKHQETA-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H14F5NO3S/c1-27-18(26)9-7-5-3-2-4-6-8(7)28-17(9)24-16(25)10-11(19)13(21)15(23)14(22)12(10)20/h2-6H2,1H3,(H,24,25)
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| Chemical Name |
methyl 2-[(2,3,4,5,6-pentafluorobenzoyl)amino]-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxylate
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| Synonyms |
TP 2 TP-2 TP2
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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 | 2.3845 mL | 11.9226 mL | 23.8453 mL | |
| 5 mM | 0.4769 mL | 2.3845 mL | 4.7691 mL | |
| 10 mM | 0.2385 mL | 1.1923 mL | 2.3845 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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