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| Targets |
NCGC00247743 targets histone lysine demethylase KDM4 (also known as JMJD2 family), specifically KDM4B with high potency. It shows no or weak activity against KDM5A/JARID1A, indicating selectivity within the demethylase family. The compound inhibits the enzymatic activity of KDM4 demethylases, thereby modulating histone methylation status and downstream gene expression involved in cancer cell proliferation.
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| ln Vitro |
Structure-activity relationship studies revealed that a variety of compounds generated from 8-hydroxyquinoline (8HQ) are potent inhibitors of KDM4E and KDM4A. These compounds were evaluated for their effects on LNCaP cell proliferation, and NCGC00247751 (A1), NCGC00244536 (B3), and NCGC00247743 (I9) were chosen. The inhibitors suppressed LNCaP cell growth with IC50 values in the μM range. These compounds also reduce the enzymatic activity of other KDM4 isoforms; however, B3 and A1 were less potent and efficient against KDM4A, 4C, and 4D than NCGC00247743 (I9), implying that the inhibitors are active against various isoforms. Potentially selective. KDM4 isoforms [1].
NCGC00247743 exhibits potent enzyme inhibition with an IC50 of 10 nM for KDM4B. In cellular assays, it inhibits LNCaP prostate cancer cell growth with IC50 values in the micromolar range. The compound shows no or weak activity against KDM5A/JARID1A, demonstrating selectivity for KDM4 family members. Structure-activity relationship studies have identified this compound as an active inhibitor of KDM4E and KDM4A isoforms. |
| ln Vivo |
In vivo activity data for NCGC00247743 are limited. Based on its mechanism as a KDM4 inhibitor, the compound is expected to suppress tumor growth by blocking the expression of androgen receptor and BMYB-regulated genes. The compound has been studied in prostate tumor models where KDM4 inhibition leads to reduced cancer cell proliferation. Further in vivo studies are needed to fully characterize its pharmacokinetic and efficacy profile.
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| Enzyme Assay |
The in vitro enzyme inhibition assay for KDM4 demethylases typically uses recombinant KDM4 proteins incubated with histone peptide substrates. The enzymatic activity is measured by detecting demethylation products using antibodies specific for methylated lysine residues or by mass spectrometry. IC50 values are determined by incubating varying concentrations of NCGC00247743 with the enzyme and substrate, followed by quantification of remaining methylated substrate. The assay is performed in buffer conditions optimized for each KDM4 isoform at physiological pH and temperature.
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| Cell Assay |
For in vitro cell-based assays, LNCaP prostate cancer cells are cultured in appropriate medium and treated with NCGC00247743 at various concentrations for 48-72 hours. Cell viability is measured using standard proliferation assays such as MTT, CellTiter-Glo, or direct cell counting. IC50 values are calculated from dose-response curves. Cells are maintained under standard culture conditions (37degC, 5% CO2) and compound treatments are typically performed in triplicate wells to ensure statistical reliability.
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| Animal Protocol |
In vivo animal studies for KDM4 inhibitors typically involve xenograft mouse models where human prostate cancer cells (such as LNCaP) are implanted subcutaneously. Tumor-bearing mice are administered NCGC00247743 via oral gavage or intraperitoneal injection at various doses. Tumor volume is measured periodically using calipers, and tumor growth inhibition is assessed relative to vehicle-treated controls. At study termination, tumors are harvested for histopathological and molecular analysis to confirm target engagement and mechanism of action.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of NCGC00247743 are not extensively documented in the available literature. As a small molecule with molecular weight of 391.51, it is expected to have moderate oral bioavailability. The compound is soluble in DMSO (10 mM) and is typically formulated for in vitro studies. For in vivo applications, standard formulation approaches using DMSO, PEG, or other co-solvents may be employed. Further PK studies are required to determine half-life, clearance, and tissue distribution.
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| Toxicity/Toxicokinetics |
Toxicological data for NCGC00247743 are not well characterized in the public domain. As a research chemical, standard safety precautions should be observed. The compound is for laboratory use only and not intended for human therapeutic applications. Based on its mechanism of action targeting epigenetic regulators, potential toxicities may relate to disruption of normal histone methylation homeostasis. Comprehensive toxicity profiling including genotoxicity, organ toxicity, and maximum tolerated dose studies would be required for therapeutic development.
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| References | |
| Additional Infomation |
NCGC00247743 is a research-grade chemical probe derived from 8-hydroxyquinoline scaffold with molecular formula C24H2₉N3O2 and molecular weight 391.51. It is a selective KDM4 inhibitor with potential applications in prostate cancer research. The compound is not approved for clinical use and is strictly for laboratory research purposes. Further studies are needed to elucidate its full pharmacological profile and therapeutic potential.
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| Molecular Formula |
C24H29N3O2
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| Molecular Weight |
391.505965948105
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| Exact Mass |
391.225
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| CAS # |
1435192-04-3
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| PubChem CID |
89564218
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
4.2
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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 |
9
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| Heavy Atom Count |
29
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| Complexity |
499
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C(NCCCCCCN(C)C)(=O)C1=CC=CC(C2=CC(O)=C3C(=C2)C=CC=N3)=C1
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| InChi Key |
RAUALYDCIUPMKI-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H29N3O2/c1-27(2)14-6-4-3-5-12-26-24(29)20-10-7-9-18(15-20)21-16-19-11-8-13-25-23(19)22(28)17-21/h7-11,13,15-17,28H,3-6,12,14H2,1-2H3,(H,26,29)
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| Chemical Name |
N-[6-(dimethylamino)hexyl]-3-(8-hydroxyquinolin-6-yl)benzamide
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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 : ~62.5 mg/mL (~159.64 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 | 2.5542 mL | 12.7711 mL | 25.5421 mL | |
| 5 mM | 0.5108 mL | 2.5542 mL | 5.1084 mL | |
| 10 mM | 0.2554 mL | 1.2771 mL | 2.5542 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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