| Size | Price | Stock | Qty |
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| 5mg |
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| Targets |
DHODH-IN-11 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-11 is a weak inhibitor of DHODH with an IC₅₀ >100 µM. The compound's low potency is attributed to the poor stereochemistry of the oxime substructure. Its pKa of 5.03 influences its ionization state and physicochemical properties. DHODH-IN-11 serves as a research tool for studying structure-activity relationships of DHODH inhibitors.
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| ln Vitro |
Compound 14a, which has a furan ring and is associated with the structure of leflunomide, was created. Under physiological pH circumstances, compound 14a undergoes ring 4 cleavage to yield the equivalent cyanooxime DHODH-IN-11 (compound 14b). It has been established that DHODH-IN-14 is a DHODH inhibitor; nevertheless, the oxime substructure's unfavorable stereochemistry may be the cause of its poor efficacy [1].
In vitro, DHODH-IN-11 is a weak inhibitor of dihydroorotate dehydrogenase (DHODH) with an IC₅₀ >100 µM. The compound has a pKa of 5.03. 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-11 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-11 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 (IC₅₀ >100 µM) 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-11 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-11 shows weak inhibition with an IC₅₀ >100 µM.
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| Cell Assay |
In vitro cellular experiments with DHODH-IN-11 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 (IC₅₀ >100 µM) 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-11 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 (IC₅₀ >100 µM) 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-11 are not extensively characterized. The compound has molecular formula C₁₅H₁₁N₃O₂ and molecular weight 265.27. As a small molecule (molecular weight 265.27), it is expected to have reasonable oral bioavailability and tissue distribution. The compound has a pKa of 5.03, which influences its ionization state and physicochemical properties. Storage: protect from light, store at -20°C. Purity is typically ≥98%. 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-11 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. Cytotoxicity studies in cell-based assays may be performed to assess the compound's safety profile.
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| References | |
| Additional Infomation |
DHODH-IN-11 (CAS 1263303-95-2) is a Leflunomide derivative and a weak inhibitor of dihydroorotate dehydrogenase (DHODH). The compound has molecular formula C₁₅H₁₁N₃O₂ and molecular weight 265.27. DHODH-IN-11 has a pKa of 5.03. It is a synthetic derivative of the immunosuppressive agent Leflunomide and functions as a weak DHODH inhibitor. The compound does not inhibit DHODH with appreciable potency (IC₅₀ >100 µM). DHODH-IN-11 is also known as Compound 14b and serves as a research tool for studying structure-activity relationships of DHODH inhibitors. Purity is typically ≥98%. Storage: protect from light, store at -20°C.
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| Molecular Formula |
C15H11N3O2
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| Molecular Weight |
265.266742944717
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| Exact Mass |
265.085
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| CAS # |
1263303-95-2
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| PubChem CID |
51031365
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
4.1
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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 |
3
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| Heavy Atom Count |
20
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| Complexity |
410
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(/C(/C#N)=N/O)NC1C=CC(=CC=1)C1C=CC=CC=1
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| InChi Key |
YFGFEIDPJVPFOM-NBVRZTHBSA-N
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| InChi Code |
InChI=1S/C15H11N3O2/c16-10-14(18-20)15(19)17-13-8-6-12(7-9-13)11-4-2-1-3-5-11/h1-9,20H,(H,17,19)/b18-14+
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| Chemical Name |
(2E)-2-cyano-2-hydroxyimino-N-(4-phenylphenyl)acetamide
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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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 : ~125 mg/mL (~471.22 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.08 mg/mL (7.84 mM) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 20.8 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.7697 mL | 18.8487 mL | 37.6974 mL | |
| 5 mM | 0.7539 mL | 3.7697 mL | 7.5395 mL | |
| 10 mM | 0.3770 mL | 1.8849 mL | 3.7697 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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