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| Targets |
The primary target is KDM4 (histone lysine demethylase 4), a family of enzymes that remove methyl groups from histone H3 lysine 9 and 36, thereby regulating gene expression and chromatin structure. KDM4B-IN-B3 specifically inhibits KDM4 with an IC50 of 10 nM. The compound blocks the binding of KDM4B to the PLK1 promoter, suppressing the expression of AR and BMYB-regulated genes. By inhibiting KDM4 activity, the compound alters histone methylation patterns and gene expression, leading to anticancer effects. The high potency (10 nM IC50) indicates strong binding affinity and effective enzyme inhibition.
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| ln Vitro |
NCGC00244536 exhibits over 100-fold selectivity against immortalized epithelial cell lines PrEC1 and PrEC4, and high sensitivity (IC50=40 nM) against rapidly proliferating AR-negative PC3 cells. NCGC00244536 inhibits androgen-stimulated LNCaP cell growth and efficiently blocks AR cell lines, including VCaP and LNCaP, with an IC50 in the submicromolar range. With a micromolar IC50, NCGC00244536 also successfully suppresses the growth of various cancer cell lines, such as the MDA-MB2 and MCF-7 breast cancer cell lines[1].
KDM4B-IN-B3 inhibits KDM4 enzymatic activity with an IC50 of 10 nM. It shows over 100-fold selectivity for immortalized epithelial cell lines PrEC1 and PrEC4, with high sensitivity to rapidly proliferating AR-negative PC3 cells (IC50=40 nM). The compound inhibits androgen-stimulated LNCaP cell growth and effectively blocks AR cell lines including VCaP and LNCaP with IC50 values in the sub-micromolar range. It also successfully inhibits the growth of various cancer cell lines, including MDA-MB-231 and MCF-7 breast cancer cell lines, with micromolar IC50 values. |
| ln Vivo |
In addition to showing no substantial harm and appearing normal, treatment with NCGC00244536 greatly slowed the growth of the tumors in the animals. The highly cellular, distinct, and fibrotic tumors treated with NCGC00244536 were clearly shown by histological data [1].
KDM4B-IN-B3 inhibits the in vivo growth of tumors derived from PC3 cells and ex vivo human prostate cancer explants. Treatment significantly slows tumor growth in animals. Histological data clearly shows highly cellular, fibrotic tumors in NCGC00244536-treated animals. Importantly, treatment shows no substantial harm and animals appear normal, suggesting a favorable safety profile. The compound's efficacy in both cell line-derived xenografts and patient-derived explants demonstrates its potential as a therapeutic agent for KDM4-driven cancers. |
| Enzyme Assay |
No specific non-cell assay protocol is available for KDM4B-IN-B3. For KDM4 inhibitors, standard cell-free assays use recombinant KDM4 enzyme and biotinylated histone H3 peptides as substrates. After compound incubation, demethylation is detected by AlphaScreen, ELISA, or mass spectrometry to determine IC50 values. These assays can provide quantitative data on the compound's potency and selectivity for different KDM4 family members. Kinetic studies may also be performed to determine the mechanism of inhibition (competitive, non-competitive, or uncompetitive).
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| Cell Assay |
No specific cell-based assay protocol is available for KDM4B-IN-B3. For KDM4 inhibitors, cellular assays involve treatment of cancer cell lines (e.g., PC3, LNCaP, MDA-MB-231, MCF-7) with compound for 48-72 hours. Following treatment, cell viability is measured using MTT or CellTiter-Glo assays to determine IC50 values. Additionally, western blot analysis of histone methylation marks (H3K9me3, H3K36me3) can confirm target engagement and demonstrate the compound's ability to modulate histone methylation in cells. Gene expression analysis by qPCR can assess changes in AR-regulated and other target genes.
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| Animal Protocol |
In vivo efficacy is evaluated using a PC3 cell-derived xenograft model in immunocompromised mice. The compound is administered (route not specified) for 2-4 weeks. Tumor volume is measured regularly, and animals are monitored for body weight and general health. At the end of the study, tumors are collected for histological analysis to assess treatment effects on tumor cellularity, fibrosis, and other pathological features. Ex vivo human prostate cancer explants may also be used to evaluate compound efficacy in patient-derived tissues.
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| ADME/Pharmacokinetics |
No detailed pharmacokinetic data is publicly available for KDM4B-IN-B3. The compound has a molecular weight of 382.45 and formula C25H22N2O2. It has 2 hydrogen bond donors, 3 hydrogen bond acceptors, and 6 rotatable bonds. The molecular complexity is rated at 519. The compound is soluble in DMSO. Powder can be stored at -20°C for 3 years or at 4°C for 2 years; in solvent at -80°C for 6 months or at -20°C for 1 month. Comprehensive pharmacokinetic studies would be required for therapeutic development.
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| Toxicity/Toxicokinetics |
No detailed toxicology data is publicly available for KDM4B-IN-B3. Preliminary in vivo studies indicate no substantial harm and normal appearance of treated animals. Comprehensive toxicology would require standard GLP studies including genotoxicity, hERG cardiac safety, and repeated-dose toxicity in two species. The compound's selectivity for KDM4 over other histone demethylases may contribute to a favorable safety profile. However, as an epigenetic modifier, careful evaluation of potential long-term effects on gene expression and cellular differentiation would be necessary. The compound is for research use only.
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| References | |
| Additional Infomation |
KDM4B-IN-B3 is also known as NCGC00244536 and NCGC-00244536. It has a molecular weight of 382.45, formula C25H22N2O2, and purity ≥98%. The chemical name is 3-(8-hydroxy-6-quinolinyl)-N-(3-phenylpropyl)-benzamide. It appears as a light yellow to green yellow solid powder. The SMILES notation is O([H])C1=C2C(C([H])=C([H])C([H])=N2)=C([H])C(=C1[H])C1C([H])=C([H])C([H])=C(C(N([H])C([H])([H])C([H])([H])C([H])([H])C2C([H])=C([H])C([H])=C([H])C=2[H])=O)C=1[H]. The compound has an HS Tariff Code of 2934.99.9001. No clinical trial status has been identified.
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| Molecular Formula |
C25H22N2O2
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| Molecular Weight |
382.4544
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| Exact Mass |
382.17
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| Elemental Analysis |
C, 78.51; H, 5.80; N, 7.32; O, 8.37
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| CAS # |
2003260-55-5
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| PubChem CID |
127030711
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| Appearance |
Light yellow to green yellow solid powder
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
29
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| Complexity |
519
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O([H])C1=C2C(C([H])=C([H])C([H])=N2)=C([H])C(=C1[H])C1C([H])=C([H])C([H])=C(C(N([H])C([H])([H])C([H])([H])C([H])([H])C2C([H])=C([H])C([H])=C([H])C=2[H])=O)C=1[H]
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| Synonyms |
KDM4B-IN-B3; KDM4B IN B3; KDM4BINB3; NCGC00244536; NCGC-00244536; NCGC 00244536;
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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 : ~36.67 mg/mL (~95.88 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.75 mg/mL (7.19 mM) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 27.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 + to the above solution and mix evenly; then add 450 μL normal saline to 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 | 2.6147 mL | 13.0736 mL | 26.1472 mL | |
| 5 mM | 0.5229 mL | 2.6147 mL | 5.2294 mL | |
| 10 mM | 0.2615 mL | 1.3074 mL | 2.6147 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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