| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
|
| Targets |
Dihydroorotate dehydrogenase (DHODH) (IC50 = 4.3 μM)
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|---|---|
| ln Vitro |
The hydroxyfuran analog of A771726, DHODH-IN-13 (compound 7a), is stable in physiological environments. A BQN-like position, in which the deprotonated furan hydroxyl group faces Arg136 rather than Tyr356, is obtained when DHODH-IN-13 is docked to the DHODH active site in silico[1]. This pose effectively mimics the carboxyl group of BQN and related compounds.
|
| Enzyme Assay |
Inhibition of DHODH [1]
The final products 7a–n were assessed for their DHODH inhibitory activity on rat liver mitochondrial/microsomal membranes. A procedure adapted from the literature was employed (see Experimental), in which oxidation of DHO to ORO is monitored by following the concomitant reduction of the chromophore 2,6-dichlorophenolindophenol (DCIP); A771726 and BQN were taken as references. The reduction of DCIP was detected by the decrease in absorbance at 650 nm. |
| References | |
| Additional Infomation |
Based on some structural analogies with leflunomide and brequinar, two well-known inhibitors of dihydroorotate dehydrogenase (DHODH), a new series of products was designed, by joining the substituted biphenyl moiety to the 4-hydroxy-1,2,5-oxadiazol-3-yl scaffold through an amide bridge. The compounds were studied for their DHODH inhibitory activity on rat liver mitochondrial/microsomal membranes. The activity was found to be closely dependent on the substitution pattern at the biphenyl system; the most potent products were those bearing two or four fluorine atoms at the phenyl adjacent to the oxadiazole ring. A molecular modeling study suggested that these structures might have a brequinar-like binding mode. The greater potency of fluorinated analogs may depend partly on enhanced interactions with the hydrophobic ubiquinone channel, and partly on the role of fluorine in stabilizing the putative bioactive conformation. [1]
|
| Molecular Formula |
C10H6F3N3O3
|
|---|---|
| Molecular Weight |
273.17
|
| Exact Mass |
273.036
|
| CAS # |
1364791-86-5
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| PubChem CID |
57381308
|
| Appearance |
Typically exists as solid at room temperature
|
| LogP |
1.9
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
2
|
| Heavy Atom Count |
19
|
| Complexity |
414
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C1=CC(=CC=C1C(F)(F)F)NC(=O)C2=NONC2=O
|
| InChi Key |
SYZRMPPEMZWUSK-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C10H6F3N3O3/c11-10(12,13)5-1-3-6(4-2-5)14-8(17)7-9(18)16-19-15-7/h1-4H,(H,14,17)(H,16,18)
|
| Chemical Name |
4-oxo-N-[4-(trifluoromethyl)phenyl]-1,2,5-oxadiazole-3-carboxamide
|
| Synonyms |
DHODHIN13; DHODH-IN-13; 1364791-86-5; CHEMBL1946653; 4-hydroxy-N-[4-(trifluoromethyl)phenyl]-1,2,5-oxadiazole-3-carboxamide; BDBM50363553; DHODH IN 13
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| 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 | 3.6607 mL | 18.3036 mL | 36.6072 mL | |
| 5 mM | 0.7321 mL | 3.6607 mL | 7.3214 mL | |
| 10 mM | 0.3661 mL | 1.8304 mL | 3.6607 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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