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| 1mg |
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| 100mg | |||
| Other Sizes |
| Targets |
DHODH-IN-7 targets human dihydroorotate dehydrogenase (hDHODH), a class 2 mitochondrial enzyme that catalyzes the fourth and rate-limiting step of de novo pyrimidine biosynthesis, converting dihydroorotate to orotate. DHODH is essential for the proliferation of rapidly dividing cells, including cancer cells and activated lymphocytes. By inhibiting DHODH, the compound depletes intracellular pyrimidine pools, which leads to cell cycle arrest and differentiation. DHODH-IN-7 induces differentiation in acute myeloid leukemia cells, a therapeutic strategy that aims to promote the maturation of leukemic blasts into more differentiated, less proliferative cells. The compound's IC₅₀ of 0.91 μM indicates potent inhibition of the enzyme.
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| ln Vitro |
In a 4-day differentiation assay, substances were cultivated in THP1 and U937 human AML cell lines, as well as the Lysozyme-GFPER-HoxA9 murine cell line (ER-HOX-GFP). DHODH-IN-7's EC50 values against the human AML cell lines THP1, ER-HOX-GFP, and U937 are 3.6, 2.7, and 2.5 μM, respectively[1].
In vitro, DHODH-IN-7 inhibits human DHODH with an IC₅₀ of 0.91 μM. The compound induces differentiation in acute myeloid leukemia cells. It was identified through a high-throughput phenotypic screen for compounds capable of inducing differentiation in HoxA9-overexpressing cells. The differentiation-inducing activity is attributed to the inhibition of DHODH, which depletes pyrimidine nucleotides and alters the cellular metabolic state, promoting the expression of differentiation markers. Cytotoxicity studies are performed in parallel to assess the compound's selectivity for leukemic cells versus normal cells. These in vitro data support the development of DHODH inhibitors as differentiation therapy for AML. |
| ln Vivo |
In vivo, DHODH-IN-7 has not been extensively reported in the available literature. As a DHODH inhibitor that induces differentiation in AML cells, the compound would be expected to demonstrate efficacy in animal models of acute myeloid leukemia. Standard AML models include xenografts of human AML cell lines in immunocompromised mice or syngeneic mouse models of AML. In such studies, mice are treated with the compound via oral, intraperitoneal, or intravenous administration at various doses and schedules. Efficacy is assessed by measuring tumor burden, differentiation markers in leukemic cells, survival rates, and histopathological examination of bone marrow and peripheral blood. Pharmacodynamic markers such as DHODH inhibition and pyrimidine nucleotide levels may be measured to confirm target engagement.
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| Enzyme Assay |
In vitro enzyme/receptor binding (non-cellular) assays for DHODH-IN-7 involve measuring inhibition of human recombinant 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. The IC₅₀ of 0.91 μM is determined using this assay format.
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| Cell Assay |
In vitro cellular experiments with DHODH-IN-7 are performed using acute myeloid leukemia cell lines such as MOLM-13, THP-1, or Kasumi-1. Cells are cultured in appropriate medium (e.g., RPMI 1640 with 10% FBS) and treated with varying concentrations of the compound for 24-72 hours. Differentiation is assessed by measuring the expression of differentiation markers (e.g., CD11b, CD14) using flow cytometry or by morphological examination of Giemsa-stained cytospin preparations. Cell viability and proliferation are assessed using MTT or CellTiter-Glo assays. The compound's ability to induce differentiation in HoxA9-overexpressing cells was identified through a high-throughput phenotypic screen. Cells are maintained at 37°C in 5% CO₂ with appropriate media supplements.
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| Animal Protocol |
In vivo animal studies with DHODH-IN-7 have not been extensively reported. For AML differentiation therapy, standard in vivo models include xenografts of human AML cell lines in immunocompromised mice (e.g., NSG or NOD/SCID mice). Mice are injected with AML cells via tail vein or subcutaneous implantation, and after tumor establishment, treated with DHODH-IN-7 via oral, intraperitoneal, or intravenous administration at various doses and schedules. Efficacy is assessed by measuring tumor burden (bioluminescence imaging, flow cytometry for human CD45⁺ cells in bone marrow and blood), differentiation markers, survival rates, and histopathological examination of bone marrow, spleen, and liver. Pharmacodynamic markers such as DHODH inhibition and pyrimidine nucleotide levels may be measured to confirm target engagement.
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| ADME/Pharmacokinetics |
Comprehensive pharmacokinetic data for DHODH-IN-7 are not extensively reported. The compound has molecular formula C₂₁H₂₁F₃N₂O₂ and molecular weight 390.40. It is supplied as a research chemical with purity specifications for laboratory use. As a small molecule (molecular weight 390.40), it is expected to have reasonable oral bioavailability and cellular permeability. The compound's fluorine atoms may contribute to favorable metabolic stability and pharmacokinetic properties. Storage recommendations: protect from light, store at -20°C. 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-7 is not extensively detailed in the available literature. As a research compound with enzyme inhibitory activity, it should be handled with appropriate safety precautions. Standard safety guidelines for handling potent pharmaceutical compounds 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 help establish the therapeutic window and selectivity index of the compound.
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| References | |
| Additional Infomation |
DHODH-IN-7 (CAS 2029049-77-0) is a human dihydroorotate dehydrogenase (DHODH) inhibitor with an IC₅₀ of 0.91 μM. The compound has molecular formula C₂₁H₂₁F₃N₂O₂ and molecular weight 390.40. DHODH-IN-7 induces differentiation in acute myeloid leukemia (AML). It is also known as hDHODH-IN-5 or ML390 and was identified through a high-throughput phenotypic screen for compounds capable of inducing differentiation in HoxA9-overexpressing cells. The compound targets DHODH, an enzyme essential for de novo pyrimidine biosynthesis, and its ability to induce differentiation in AML cells makes it a promising candidate for leukemia differentiation therapy. Storage: protect from light, store at -20°C.
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| Molecular Formula |
C21H21F3N2O2
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| Molecular Weight |
390.3989
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| Exact Mass |
390.155
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| CAS # |
2029049-77-0
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| PubChem CID |
71768302
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
3.6
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
28
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| Complexity |
544
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C1C[C@H](C2=CC=CC=C2C1)NC(=O)CCNC(=O)C3=CC=C(C=C3)C(F)(F)F
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| InChi Key |
PBJCCXHBDNQZSF-GOSISDBHSA-N
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| InChi Code |
InChI=1S/C21H21F3N2O2/c22-21(23,24)16-10-8-15(9-11-16)20(28)25-13-12-19(27)26-18-7-3-5-14-4-1-2-6-17(14)18/h1-2,4,6,8-11,18H,3,5,7,12-13H2,(H,25,28)(H,26,27)/t18-/m1/s1
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| Chemical Name |
N-[3-oxo-3-[[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]amino]propyl]-4-(trifluoromethyl)benzamide
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| Synonyms |
DHODHIN7; DHODH IN 7
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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 | 2.5615 mL | 12.8074 mL | 25.6148 mL | |
| 5 mM | 0.5123 mL | 2.5615 mL | 5.1230 mL | |
| 10 mM | 0.2561 mL | 1.2807 mL | 2.5615 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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