| Size | Price | Stock | Qty |
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| 5mg |
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| Other Sizes |
| Targets |
DHODH-IN-1 targets dihydroorotate dehydrogenase (DHODH), a mitochondrial enzyme that catalyzes the conversion of dihydroorotate to orotate in the de novo pyrimidine biosynthesis pathway. By inhibiting DHODH with an IC50 of 25 nM, it reduces the production of pyrimidine nucleotides, leading to cell cycle arrest and apoptosis in rapidly dividing cells.
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| ln Vitro |
Compound 18d, DHODH-IN-1, significantly suppresses the growth of Jurkat cells (IC50=0.02 μM)[1]. In cells, DHODH-IN-1 (4, 20, 100 nM) inhibits the measles virus's ability to replicate[1]. When cells are transfected with ssRNA molecules, IN-1 (0.008, 0.04, 0.2, 1, 5 μM) enhances the expression of an ISRE-luciferase reporter gene[1].
In vitro, DHODH-IN-1 potently inhibits DHODH with an IC50 of 25 nM. It is an inhibitor of the pyrimidine biosynthesis pathway. The compound's potent DHODH inhibition makes it a valuable tool for studying pyrimidine metabolism and its role in cell proliferation, immune function, and cancer. |
| ln Vivo |
The t1/2 of DHODH-IN-1 (compound 18d) is 27–41 min[1].
In vivo, DHODH-IN-1 is used as a research tool to study the effects of DHODH inhibition. As a DHODH inhibitor, it can be administered to animal models to study the role of pyrimidine biosynthesis in various diseases, including cancer, autoimmune disorders, and viral infections. Its ability to block pyrimidine synthesis may have immunosuppressive and antiproliferative effects. Detailed in vivo pharmacokinetic and efficacy studies are available. |
| Enzyme Assay |
In vitro enzyme assays for DHODH-IN-1 involve measuring its inhibition of DHODH activity. Recombinant DHODH is incubated with increasing concentrations of the compound, dihydroorotate, and coenzyme Q in assay buffer. The oxidation of dihydroorotate is measured spectrophotometrically at 340 nm or by monitoring the reduction of CoQ. IC50 values are calculated from dose-response curves.
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| Cell Assay |
Cell Proliferation Assay[1]
Cell Types: Jurkat cells Tested Concentrations: 0.00001, 0.0001, 0.001, 0.01, 0.1, 1, 10 μM Incubation Duration: 72 hrs (hours) Experimental Results: Strongly inhibited Jurkat cells proliferation (IC50=0.02 μM). For in vitro cell-based assays, cells are cultured and treated with DHODH-IN-1 at various concentrations. Pyrimidine depletion is confirmed by measuring the incorporation of radiolabeled uridine or by assessing the levels of pyrimidine nucleotides using LC-MS. Cell proliferation is assessed by MTT or CellTiter-Glo assays. Cell cycle analysis is performed by propidium iodide staining and flow cytometry. |
| Animal Protocol |
In vivo animal studies with DHODH-IN-1 are conducted in models of cancer, autoimmune diseases, or viral infections. The compound is administered orally or intraperitoneally at doses determined from pharmacokinetic studies. Efficacy is measured by tumor growth inhibition, reduction in disease severity, or viral load. Pharmacodynamic markers such as pyrimidine nucleotide levels are measured in tissues.
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| ADME/Pharmacokinetics |
DHODH-IN-1 (CAS: 1800296-63-2) has a molecular weight of 403.40 g/mol and a molecular formula of C21H20F3N3O2. Appearance: solid powder. Purity: ≥98%. Solubility: DMSO. Storage: powder at -20°C. The compound is a potent DHODH inhibitor with an IC50 of 25 nM.
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| Toxicity/Toxicokinetics |
DHODH-IN-1 is a research compound and is not approved for human therapeutic use. In preclinical studies, it has shown a manageable safety profile. As a DHODH inhibitor, it may have effects on rapidly dividing cells, including immune cells. The compound's inhibition of pyrimidine biosynthesis may have immunosuppressive effects. Standard laboratory safety precautions should be followed when handling the compound.
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| References | |
| Additional Infomation |
DHODH-IN-1 (compound 18d) is a potent inhibitor of dihydroorotate dehydrogenase (DHODH) with an IC50 of 25 nM. It blocks the pyrimidine biosynthesis pathway. It has a molecular weight of 403.40 g/mol and a molecular formula of C21H20F3N3O2. It is not FDA-approved and is intended for research use only.
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| Molecular Formula |
C21H20F3N3O2
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|---|---|
| Molecular Weight |
403.40
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| Exact Mass |
403.15
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| CAS # |
1800296-63-2
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| PubChem CID |
118430456
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| Appearance |
White to off-white solid powder
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| LogP |
5.4
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
29
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| Complexity |
543
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC=C(F)C(OC2C(=NN(C3N=CC(C4CC4)=CC=3F)C=2C)OC(C)C)=C1F
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| InChi Key |
JNAABFZPXJJMPX-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H20F3N3O2/c1-11(2)28-21-18(29-19-15(22)5-4-6-16(19)23)12(3)27(26-21)20-17(24)9-14(10-25-20)13-7-8-13/h4-6,9-11,13H,7-8H2,1-3H3
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| Chemical Name |
5-cyclopropyl-2-[4-(2,6-difluorophenoxy)-5-methyl-3-propan-2-yloxypyrazol-1-yl]-3-fluoropyridine
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| Synonyms |
DHODHIN1 DHODH IN 1
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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: ~100 mg/mL (~247.9 mM; with ultrasonication)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.20 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% Saline (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 DMSO stock solution (25.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and 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 | 2.4789 mL | 12.3946 mL | 24.7893 mL | |
| 5 mM | 0.4958 mL | 2.4789 mL | 4.9579 mL | |
| 10 mM | 0.2479 mL | 1.2395 mL | 2.4789 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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