| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
AS-1134900 specifically targets the metabolic enzyme malic enzyme 1 (ME1). ME1 is a cytosolic enzyme that catalyzes the oxidative decarboxylation of malate to pyruvate, producing NADPH from NADP+. As an uncompetitive allosteric inhibitor, AS-1134900 binds only to the enzyme-substrate complex, preventing catalytic turnover. This mechanism is highly specific and reduces the risk of off-target effects.
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| ln Vitro |
In vitro, AS-1134900 potently inhibits the catalytic activity of recombinant human ME1 with an IC50 of 0.73 microM. In cell-based assays, treatment with AS-1134900 leads to a reduction in the cellular NADPH/NADP+ ratio and increases reactive oxygen species (ROS) levels. This metabolic stress impairs the growth of cancer cells that are dependent on ME1 for lipogenesis and protection against oxidative stress. It is a valuable tool for studying cancer cell metabolism.
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| ln Vivo |
In vivo, AS-1134900 has shown potential in cancer models. Studies have demonstrated that inhibition of ME1 with this compound can suppress tumor growth in xenograft mouse models. By blocking ME1, the compound disrupts the tumor's ability to manage oxidative stress and synthesize lipids, both of which are essential for rapid proliferation. These preclinical results validate ME1 as a promising therapeutic target for oncology.
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| Enzyme Assay |
For non-cell-based enzyme inhibition assays, recombinant human ME1 is expressed in E. coli and purified to homogeneity. The enzyme is incubated with varying concentrations of AS-1134900 (0-100 microM) in a 96-well plate in an assay buffer (50 mM Tris-HCl, 50 mM KCl, 10 mM MgCl2, pH 7.4). The reaction is started by adding the substrate (L-malic acid) and cofactor (NADP+). The production of NADPH is measured continuously by the increase in absorbance at 340 nm using a plate reader. The IC50 is calculated.
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| Cell Assay |
For in vitro cell assays, cancer cell lines known to be dependent on ME1 (e.g., pancreatic or lung cancer cells) are seeded in 96-well plates. After 24 hours, cells are treated with a 2-fold dilution series of AS-1134900 (e.g., 0.1-100 microM) for 48-72 hours. Cell viability is measured using a standard MTT or CellTiter-Glo assay. Additionally, intracellular NADPH/NADP+ ratios are measured using a commercially available colorimetric or fluorometric detection kit to confirm target engagement.
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| Animal Protocol |
For in vivo animal models, a standard xenograft mouse model is used. Immunodeficient mice (nude) are subcutaneously injected with ME1-dependent cancer cells (e.g., H1299 lung cancer cells). Once tumors reach 100-150 mm3, mice are randomized into treatment groups. AS-1134900 is administered daily via intraperitoneal (IP) injection at doses ranging from 10-50 mg/kg. Tumor volume is measured every 2-3 days with calipers. Body weight is monitored to assess tolerability. At study endpoint, tumors are excised for analysis of ME1 activity and NADPH levels.
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| ADME/Pharmacokinetics |
As a small molecule, the pharmacokinetic properties of AS-1134900 would be evaluated in rodent models. A typical PK study involves administering a single IV (1 mg/kg) and PO (10 mg/kg) dose of AS-1134900 to Sprague-Dawley rats. Blood samples are collected at multiple time points (0-24 hours). Plasma concentrations are analyzed by LC-MS/MS. Non-compartmental analysis (NCA) is used to determine IV clearance (CL), volume of distribution (Vd), half-life (T1/2), and oral bioavailability (F%). These parameters guide the dosing regimen for efficacy studies.
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| Toxicity/Toxicokinetics |
AS-1134900 is a preclinical research compound, and formal toxicology data is not publicly available. In vitro safety profiling would be conducted using a panel of 50-100 off-targets, including GPCRs, ion channels (e.g., hERG), and kinases. Dose-limiting toxicity in animal models would be determined by conducting a maximum tolerated dose (MTD) study. Mice would be treated with increasing doses of AS-1134900 daily for 5 days, and severe toxicity (weight loss >20%, death) would be used to define the MTD.
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| Additional Infomation |
AS-1134900 is a research tool and is not approved for clinical use. Malic enzyme 1 (ME1) is considered a "metabolic checkpoint" in cancer. It is frequently upregulated in tumors to support rapid proliferation and to counter oxidative stress. By inhibiting ME1, AS-1134900 increases oxidative stress and reduces lipid synthesis, which are synthetic lethal vulnerabilities in certain cancers. This compound is a valuable chemical probe for validating ME1 as an anti-cancer target. Its uncompetitive mechanism of inhibition (binding only to the enzyme-substrate complex) often confers high selectivity and a lower risk of toxicity compared to competitive inhibitors.
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| Molecular Formula |
C25H22N8S
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|---|---|
| Molecular Weight |
466.56
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| Exact Mass |
466.168
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| CAS # |
149760-98-5
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| PubChem CID |
44210892
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| Appearance |
White to off-white solid powder
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| LogP |
4.9
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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 |
6
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| Heavy Atom Count |
34
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| Complexity |
683
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCCC1=NC2=C(C=CN(C2=N1)CC3=CC4=C(C=C3)N=C(S4)C5=CC=CC=C5C6=NNN=N6)C
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| InChi Key |
LGDMZWWVVLGYPR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C25H22N8S/c1-3-6-21-27-22-15(2)11-12-33(24(22)28-21)14-16-9-10-19-20(13-16)34-25(26-19)18-8-5-4-7-17(18)23-29-31-32-30-23/h4-5,7-13H,3,6,14H2,1-2H3,(H,29,30,31,32)
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| Chemical Name |
6-[(7-methyl-2-propylimidazo[4,5-b]pyridin-4-yl)methyl]-2-[2-(2H-tetrazol-5-yl)phenyl]-1,3-benzothiazole
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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 : ~50 mg/mL (~107.17 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 | 2.1433 mL | 10.7167 mL | 21.4335 mL | |
| 5 mM | 0.4287 mL | 2.1433 mL | 4.2867 mL | |
| 10 mM | 0.2143 mL | 1.0717 mL | 2.1433 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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