| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| Targets |
Thr101 targets phosphomannose isomerase (PMI), histone deacetylases (HDACs), and NOX enzymes. It inhibits PMI with an IC50 of 2.9 μM and does not inhibit PMM2. PMI converts mannose-6-phosphate (Man-6-P) into fructose-6-phosphate (Fru-6-P), competing with phosphomannose mutase 2 (PMM2) for the binding site of Man-6-P. Thr101 inhibits HDAC1, HDAC3, HDAC4, HDAC5, HDAC6, HDAC7, HDAC8, and HDAC9 in a dose-dependent manner. It is also a NOX inhibitor.
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| ln Vitro |
Thr101 demonstrates in vitro inhibition of PMI with an IC50 of 2.9 μM, with specificity for PMI over PMM2. The compound also inhibits multiple HDAC isoforms in a dose-dependent manner, including HDAC1, HDAC3, HDAC4, HDAC5, HDAC6, HDAC7, HDAC8, and HDAC9. As a NOX inhibitor, it may also have antioxidant effects. Specific in vitro data, including IC50 values for HDAC inhibition and detailed assay conditions, are not extensively provided in the available literature. The compound's triple-pathway pharmacology distinguishes it from other inhibitors.
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| ln Vivo |
Thr101 demonstrates in vivo activity as a PMI inhibitor, HDAC inhibitor, and NOX inhibitor. As a PMI inhibitor, it may be useful for research of congenital disorder of glycosylation type Ia (CDG-Ia). HDAC inhibition suggests potential for epigenetic modulation and anticancer activity. NOX inhibition suggests potential for antioxidant and anti-inflammatory effects. Specific in vivo efficacy data, including dosing regimens, animal models, and detailed results, are not extensively provided in the available literature. The compound's multiple targets may provide synergistic therapeutic effects.
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| Enzyme Assay |
In vitro enzyme assays for Thr101 involve measuring PMI, HDAC, and NOX activities. For PMI assays, the enzyme is incubated with mannose-6-phosphate substrate and varying concentrations of Thr101 (typically 0.1-100 μM). The reaction is initiated by addition of enzyme and terminated by heating. Product formation (fructose-6-phosphate) is quantified by coupled enzyme assays or by HPLC. IC50 values are calculated from concentration-response curves. For HDAC assays, fluorometric or radiometric substrates are used. For NOX assays, superoxide production is measured using chemiluminescent or fluorescent probes.
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| Cell Assay |
For in vitro cell-based assays, cells are cultured in appropriate medium and treated with Thr101 at various concentrations (typically 0.1-100 μM) for 24-72 hours. PMI activity is assessed by measuring mannose-6-phosphate and fructose-6-phosphate levels by HPLC. HDAC inhibition is assessed by measuring histone acetylation by Western blot. NOX inhibition is assessed by measuring ROS levels using fluorescent probes. Cell viability is assessed using MTT or similar assays. Gene expression changes are measured by qRT-PCR. Specific protocols depend on the cell type and the target being studied.
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| Animal Protocol |
In vivo animal studies for Thr101 would typically use mouse models of CDG-Ia or cancer. The compound is administered orally or intraperitoneally at doses determined from pharmacokinetic studies. For CDG-Ia models, glycosylation defects are assessed by measuring glycoprotein levels. For cancer models, tumor growth is monitored. HDAC inhibition is assessed by measuring histone acetylation in tissues. NOX inhibition is assessed by measuring oxidative stress markers. Specific protocols using Thr101 are not extensively documented in the available literature.
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| ADME/Pharmacokinetics |
Thr101 is a selenium→sulfur substituted Ebselen derivative. It is a small molecule with multiple enzyme inhibitory activities. Detailed physicochemical properties (molecular weight, formula, solubility, stability) are not extensively provided in the available literature. As a NOX inhibitor, it may have antioxidant properties. The compound's ability to inhibit multiple targets suggests it could have broad pharmacological effects. Detailed pharmacokinetic parameters are not extensively characterized.
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| Toxicity/Toxicokinetics |
Specific toxicity data for Thr101 are not extensively provided in the available literature. As a PMI inhibitor, HDAC inhibitor, and NOX inhibitor, it would be expected to have a complex safety profile. The compound's multiple targets may lead to off-target effects. As an Ebselen derivative, it may have glutathione peroxidase-like activity, which could be protective against oxidative stress. Standard toxicology assessments would be required for therapeutic development. No specific toxicity data are reported in the available references.
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| References | |
| Additional Infomation |
6-Fluoro-2-(2-methylphenyl)-1,2-benzothiazol-3-one is a member of the benzothiazol class of compounds.
Thr101 is a selenium→sulfur substituted Ebselen derivative that uniquely delivers triple-pathway pharmacology. It is a selective inhibitor of phosphomannose isomerase (PMI) with an IC50 of 2.9 μM, with PMM2 sparing. Thr101 is also a dose-dependent inhibitor of HDAC1, HDAC3, HDAC4, HDAC5, HDAC6, HDAC7, HDAC8, and HDAC9. It is also a NOX inhibitor. The compound can be used for research of congenital disorder of glycosylation type Ia (CDG-Ia). No approved therapeutic status is reported. |
| Molecular Formula |
C14H10FNOS
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|---|---|
| Molecular Weight |
259.29870557785
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| Exact Mass |
259.046
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| CAS # |
727664-79-1
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| PubChem CID |
1510379
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| Appearance |
Off-white to yellow solid powder
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| LogP |
3.5
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
18
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| Complexity |
338
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S1C2=C(C=CC(F)=C2)C(=O)N1C1=CC=CC=C1C
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| InChi Key |
BUIZTXXZBDUOCR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C14H10FNOS/c1-9-4-2-3-5-12(9)16-14(17)11-7-6-10(15)8-13(11)18-16/h2-8H,1H3
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| Chemical Name |
6-fluoro-2-(2-methylphenyl)-1,2-benzothiazol-3-one
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| Synonyms |
Thr 101; Thr-101; Thr101
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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 | 3.8565 mL | 19.2827 mL | 38.5654 mL | |
| 5 mM | 0.7713 mL | 3.8565 mL | 7.7131 mL | |
| 10 mM | 0.3857 mL | 1.9283 mL | 3.8565 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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