| Size | Price | Stock | Qty |
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| Targets |
KDM4
The primary molecular target of KDM4C-IN-1 is the histone demethylase KDM4C (JMJD2C). It exhibits high potency with an IC50 of 8 nM against this enzyme. The compound is designed to inhibit the JmjC domain of KDM4C, which is the catalytic site responsible for the removal of methyl groups from lysine residues on histone tails, thereby modulating chromatin structure and gene expression. |
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| ln Vitro |
In vitro, KDM4C-IN-1 effectively inhibits the enzymatic activity of KDM4C, with an IC50 of 8 nM. This inhibition leads to a decrease in cell proliferation. It demonstrates growth-inhibitory effects against a variety of human cancer cell lines, including HepG2 (hepatocellular carcinoma) and A549 (lung carcinoma) with IC50 values of 0.8 uM and 1.1 uM, respectively.
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| ln Vivo |
In vivo, KDM4C-IN-1 has been investigated for its potential to slow tumor growth. As a KDM4C inhibitor, it aims to modulate epigenetic processes to inhibit the growth and progression of cancers that depend on altered epigenetic regulation. Specifically, it is considered for studying cancers such as leukemia where KDM4C is often dysregulated. However, detailed animal xenograft data is not presented in the provided summaries.
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| Enzyme Assay |
For a cell-free system, purified KDM4C enzyme and a biotinylated histone H3 peptide (with a specific methylation mark, e.g., H3K9me3) are incubated in reaction buffer. Demethylation of the peptide by KDM4C produces formaldehyde and succinate. The reaction can be quantified by measuring the production of formaldehyde using a fluorescence-based detection method, or by detecting the demethylated product via AlphaLISA or Western blot. The compound is pre-incubated with the enzyme before adding the substrate.
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| Cell Assay |
In cellular assays, cancer cells (e.g., HepG2 or A549) are seeded in multi-well plates and treated with varying concentrations of KDM4C-IN-1 (e.g., 0.1 uM to 10 uM) for 48 to 72 hours. Cell viability is measured using a colorimetric assay like MTT or a luminescence-based CellTiter-Glo assay. The IC50 value is derived from a dose-response curve. Changes in H3K9/K36 methylation levels can also be assessed by Western blot to confirm on-target activity.
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| Animal Protocol |
In vivo efficacy is typically studied in mouse xenograft models. Immunocompromised mice are subcutaneously implanted with tumor cells, such as HepG2 or A549. Once tumors reach a suitable volume, the mice are randomized and treated with KDM4C-IN-1 or a vehicle control. The route and frequency of administration (e.g., oral gavage or intraperitoneal injection) are determined by the compound's bioavailability. Tumor volume and body weight are measured regularly to assess anti-tumor activity and toxicity.
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| ADME/Pharmacokinetics |
Detailed ADME (Absorption, Distribution, Metabolism, and Excretion) data for KDM4C-IN-1 are not provided in the available literature. For in vivo experiments, the compound can be prepared in a vehicle (e.g., DMSO: Tween 80: Saline = 10:5:85 or DMSO:Corn oil=10:90) for intraperitoneal (IP) or intravenous (IV) injection, or suspended in 0.5% CMC-Na for oral dosing, as suggested in formulation guidelines.
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| Toxicity/Toxicokinetics |
Toxicological data for KDM4C-IN-1 is not presented in the summaries. The compound's safety profile is a subject of ongoing investigation as part of its preclinical development. The primary endpoint in in vivo studies is often tumor growth inhibition, with body weight change serving as an initial indicator of general toxicity. KDM4C is a potential therapeutic target in cancer, but the specific toxicities of its inhibitors are not fully characterized.
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| References | |
| Additional Infomation |
KDM4C (JMJD2C) is an oncogene that is frequently amplified and overexpressed in various human cancers, including leukemia, esophageal squamous cell carcinoma, and prostate cancer. KDM4C-IN-1 serves as a valuable tool compound for validating KDM4C as a drug target. By inhibiting KDM4C, the compound aims to increase H3K9me3 and H3K36me3 levels, leading to heterochromatin formation and suppression of oncogene expression. It is in preclinical research and has not been approved for clinical use.
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| Molecular Formula |
C14H13N5O3
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|---|---|
| Molecular Weight |
299.28
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| Exact Mass |
299.102
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| CAS # |
52348-60-4
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| PubChem CID |
823993
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| Appearance |
Orange to red solid powder
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| LogP |
0.097
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
22
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| Complexity |
602
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CN1C2=NC(=O)N(C(=O)C2=NC(=N1)C3=CC=C(C=C3)OC)C
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| InChi Key |
BVFGFWOGCVXIFG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C14H13N5O3/c1-18-13(20)10-12(16-14(18)21)19(2)17-11(15-10)8-4-6-9(22-3)7-5-8/h4-7H,1-3H3
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| Chemical Name |
3-(4-methoxyphenyl)-1,6-dimethylpyrimido[5,4-e][1,2,4]triazine-5,7-dione
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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: ≥ 3 mg/mL (10.02 mM)
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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 | 3.3414 mL | 16.7068 mL | 33.4135 mL | |
| 5 mM | 0.6683 mL | 3.3414 mL | 6.6827 mL | |
| 10 mM | 0.3341 mL | 1.6707 mL | 3.3414 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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