| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
The primary target is phosphomannose isomerase (PMI) (also known as mannose-6-phosphate isomerase, MPI). PMI catalyzes the reversible isomerization of fructose-6-phosphate to mannose-6-phosphate, a critical step in the synthesis of GDP-mannose and subsequent protein glycosylation. ML-089 is a potent, selective, and orally available PMI inhibitor, also with potential inhibition of other PMI immediate homologs.
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| ln Vitro |
ML-089 inhibits PMI with an IC50 of 1.3 uM in biochemical assays. It is membrane-permeable and effectively suppresses the conversion of fructose-6-phosphate to mannose-6-phosphate in cell-based models. It shows high selectivity for PMI over other related enzymes. It can be used for the research of congenital disorder of glycosylation Ia.
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| ln Vivo |
ML-089 is orally bioavailable in animal models, enabling in vivo studies of glycosylation disorders. It has been used to explore the biochemical and physiological consequences of PMI inhibition in living organisms. By inhibiting PMI, it allows researchers to create a pharmacological model of CDG-Ia to test potential therapies and understand disease mechanisms. Its good oral bioavailability is key for in vivo applications.
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| Enzyme Assay |
For a cell-free biochemical assay, recombinant human PMI enzyme (0.1-0.5 ug) is incubated with varying concentrations of ML-089 (0.05-10 uM) in a 96-well plate. The reaction mixture contains a substrate (fructose-6-phosphate, 0.5 mM) in 100 mM HEPES buffer (pH 7.5) with 5 mM MgCl2. After incubation at 37degC for 5-10 minutes, the reaction is stopped by heating. The product (mannose-6-phosphate) is quantified using a colorimetric enzyme-coupled assay involving phosphoglucose isomerase and glucose-6-phosphate dehydrogenase. The change in absorbance at 340 nm (NADPH consumption) is monitored to calculate the IC50.
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| Cell Assay |
For in vitro cell-based assays, CDG-Ia patient fibroblasts or HeLa cells are cultured in mannose-free or low-mannose medium. Cells are treated with ML-089 (0.1-10 uM) for 48-72 hours. The incorporation of [2-3H]mannose into cellular glycoproteins is measured to assess PMI activity. Alternatively, cell surface lectin binding (e.g., Concanavalin A) is measured by flow cytometry to detect alterations in glycosylation patterns. Cell viability is assessed by MTT or CellTiter-Glo assay to determine non-toxic concentrations.
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| Animal Protocol |
A typical in vivo protocol for a proof-of-concept study involves oral administration of ML-089 to wild-type mice at doses of 10-30 mg/kg for up to 7 days. Blood samples are collected to measure the concentration of ML-089 by LC-MS. Tissues (liver, kidney) are harvested at the endpoint. The GDP-mannose and mannose-6-phosphate levels in tissue homogenates are measured by LC-MS/MS. The glycosylation status of serum glycoproteins (e.g., transferrin) is analyzed by isoelectric focusing (IEF) or mass spectrometry to detect hypoglycosylation, mimicking the CDG-Ia phenotype.
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| ADME/Pharmacokinetics |
ML-089 (MW: 245.27) is soluble in DMSO (25 mg/mL) and can be formulated for in vivo administration (e.g., 10% DMSO, 40% PEG300, 5% Tween80, 45% Saline). It is orally bioavailable with moderate systemic exposure. The powder is stable for up to 3 years at -20degC, and solutions in DMSO are stable for up to 6 months at -80degC. Its small size and non-competitive inhibition mechanism contribute to its favorable drug-like properties.
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| Toxicity/Toxicokinetics |
ML-089 has a favorable safety profile in vitro and in vivo at the concentrations used for research (e.g., no significant acute toxicity reported at 10-30 mg/kg in mice). Specific toxicological data, such as maximum tolerated dose (MTD), is limited. However, since it targets a key step in glycosylation, systemic inhibition in vivo could potentially lead to side effects related to altered protein glycosylation. Standard safety precautions for handling enzyme inhibitors should be taken. It is not for human use.
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| Additional Infomation |
5-Fluoro-2-phenyl-1,2-benzothiazol-3-one is a member of the benzothiazol class of compounds.
ML-089 is a valuable chemical probe for studying congenital disorder of glycosylation Ia (CDG-Ia) and the broader role of PMI in glycosylation and metabolism. It is a non-competitive, membrane-permeable benzoisothiazolone derivative. It serves as a starting point for drug discovery for CDG-Ia, as there are currently no disease-modifying therapies approved. It is for research use only. |
| Molecular Formula |
C13H8FNOS
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|---|---|
| Molecular Weight |
245.272125244141
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| Exact Mass |
245.031
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| CAS # |
1306638-12-9
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| PubChem CID |
22416235
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
3.1
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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 |
17
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| Complexity |
306
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC=C(C=C1)N2C(=O)C3=C(S2)C=CC(=C3)F
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| InChi Key |
ZTQXZKHEMCRFEP-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C13H8FNOS/c14-9-6-7-12-11(8-9)13(16)15(17-12)10-4-2-1-3-5-10/h1-8H
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| Chemical Name |
5-fluoro-2-phenyl-1,2-benzothiazol-3-one
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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 : ~25 mg/mL (~101.93 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (10.19 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 0.54 mg/mL (2.20 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 5.4 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. View More
Solubility in Formulation 3: 0.54 mg/mL (2.20 mM) in 10% DMSO + 90% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Solubility in Formulation 4: 5 mg/mL (20.39 mM) in 50% PEG300 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.0771 mL | 20.3857 mL | 40.7714 mL | |
| 5 mM | 0.8154 mL | 4.0771 mL | 8.1543 mL | |
| 10 mM | 0.4077 mL | 2.0386 mL | 4.0771 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.
Products are for research use only; We do not sell to patients
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