| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
DHODH-IN-12 targets dihydroorotate dehydrogenase (DHODH), a mitochondrial enzyme that catalyzes the fourth and rate-limiting step of de novo pyrimidine biosynthesis, converting dihydroorotate to orotate. As a Leflunomide derivative, it shares structural features with the active metabolite of Leflunomide (A-771726), which is a potent DHODH inhibitor. However, DHODH-IN-12 is a weak inhibitor of DHODH. The compound's low potency is attributed to the poor stereochemistry of the oxime substructure. Its pKa of 5.07 influences its ionization state and physicochemical properties. DHODH-IN-12 serves as a research tool for studying structure-activity relationships of DHODH inhibitors.
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| ln Vitro |
Compound 12a, which has a furan ring, was developed to be structurally similar to leflunomide. Under physiological pH settings, Compound 12a undergoes ring 4 cleavage to produce the equivalent cyanooxime DHODH-IN-12 (Compound 12b). DHODH-IN-12 has been identified as a DHODH inhibitor; its low activity could be attributed to unfavorable stereochemistry of the oxime substructure [1].
In vitro, DHODH-IN-12 is a weak inhibitor of dihydroorotate dehydrogenase (DHODH). The compound has a pKa of 5.07. As a Leflunomide derivative, it is structurally related to the active metabolite of Leflunomide, which is a potent DHODH inhibitor. However, the compound's low potency is attributed to the poor stereochemistry of the oxime substructure. DHODH-IN-12 serves as a research tool for studying structure-activity relationships of DHODH inhibitors. The compound's weak activity makes it useful for understanding the structural features required for potent DHODH inhibition and for developing more potent analogs. |
| ln Vivo |
In vivo, DHODH-IN-12 has not been reported to have therapeutic applications due to its weak DHODH inhibitory activity. As a Leflunomide derivative, it may share some immunomodulatory properties with the parent compound, but its low potency limits its potential for in vivo efficacy. The compound is primarily used as a research tool for studying structure-activity relationships of DHODH inhibitors and for understanding the structural features required for potent DHODH inhibition. Detailed in vivo pharmacokinetic and toxicological data are not extensively reported in the available literature.
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| Enzyme Assay |
In vitro enzyme/receptor binding (non-cellular) assays for DHODH-IN-12 involve measuring inhibition of DHODH enzymatic activity. The assay typically uses a colorimetric method detecting the conversion of dihydroorotate to orotate coupled with the reduction of the electron acceptor (e.g., 2,6-dichloroindophenol, DCIP). The enzyme is incubated with varying concentrations of the compound, substrate (dihydroorotate), and coenzyme (ubiquinone or decylubiquinone) in assay buffer (typically 50 mM Tris-HCl, pH 8.0, with 0.1% Triton X-100). The reaction is monitored spectrophotometrically by following the decrease in absorbance at 600 nm (DCIP reduction). IC₅₀ values are calculated from concentration-response curves. DHODH-IN-12 shows weak inhibition.
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| Cell Assay |
In vitro cellular experiments with DHODH-IN-12 are not typically performed for pharmacological evaluation, as the compound is a weak DHODH inhibitor with limited biological activity. However, cellular assays may be conducted to assess its effects on cell proliferation or immune function. Lymphocytes or other proliferating cell lines are cultured in appropriate media and treated with varying concentrations of the compound. Cell proliferation is assessed using [³H]thymidine incorporation, MTT, or CellTiter-Glo assays. The compound's weak DHODH inhibitory activity limits its effects on pyrimidine biosynthesis and cell proliferation. These experiments help characterize the compound's cellular activity and compare it to more potent DHODH inhibitors.
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| Animal Protocol |
In vivo animal studies with DHODH-IN-12 are not typically performed due to its weak DHODH inhibitory activity. As a research tool for studying structure-activity relationships, the compound may be used in comparative studies to understand the structural features required for potent DHODH inhibition. However, its low potency limits its utility for in vivo efficacy studies. The compound's weak activity makes it useful as a negative control or as a tool for understanding the relationship between chemical structure and DHODH inhibitory activity.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of DHODH-IN-12 are not extensively characterized. The compound has molecular formula C₁₀H₉N₃O₂ and molecular weight 203.20. As a small molecule (molecular weight 203.20), it is expected to have reasonable oral bioavailability and tissue distribution. The compound has a pKa of 5.07, which influences its ionization state and physicochemical properties. Storage: follow manufacturer's guidelines. Detailed pharmacokinetic parameters including half-life, clearance, and bioavailability require further investigation from primary research publications.
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| Toxicity/Toxicokinetics |
Toxicological information for DHODH-IN-12 is not extensively detailed in the available literature. As a research compound with weak enzyme inhibitory activity, it should be handled with appropriate safety precautions. Standard safety guidelines for handling research chemicals apply, including use of personal protective equipment (gloves, safety goggles, lab coat), working in a well-ventilated area, and proper chemical waste disposal. The compound is intended for research use only and is not approved for human therapeutic use.
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| References | |
| Additional Infomation |
DHODH-IN-12 (CAS 1263303-93-0) is a Leflunomide derivative and a weak inhibitor of dihydroorotate dehydrogenase (DHODH) with a pKa of 5.07. The compound has molecular formula C₁₀H₉N₃O₂ and molecular weight 203.20. DHODH-IN-12 is also known as Compound 12b. The compound's weak inhibitory activity is attributed to the poor stereochemistry of the oxime substructure. As a Leflunomide derivative, it is structurally related to the immunosuppressive agent Leflunomide, but its low potency limits its therapeutic potential. DHODH-IN-12 serves as a research tool for studying structure-activity relationships of DHODH inhibitors. Purity is typically >99%.
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| Molecular Formula |
C10H9N3O2
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|---|---|
| Molecular Weight |
203.1974
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| Exact Mass |
203.069
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| CAS # |
1263303-93-0
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| PubChem CID |
6911709
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
2.9
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
15
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| Complexity |
308
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=CC=C(C=C1)NC(=O)/C(=N/O)/C#N
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| InChi Key |
TUUSDSUFAQPEOW-UKTHLTGXSA-N
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| InChi Code |
InChI=1S/C10H9N3O2/c1-7-2-4-8(5-3-7)12-10(14)9(6-11)13-15/h2-5,15H,1H3,(H,12,14)/b13-9+
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| Chemical Name |
(2E)-2-cyano-2-hydroxyimino-N-(4-methylphenyl)acetamide
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| Synonyms |
DHODHIN12; DHODH IN 12
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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 | 4.9213 mL | 24.6063 mL | 49.2126 mL | |
| 5 mM | 0.9843 mL | 4.9213 mL | 9.8425 mL | |
| 10 mM | 0.4921 mL | 2.4606 mL | 4.9213 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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