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Purity: ≥98%
NCGC00244536 (also known as KDM4B Inhibitor B3; KDM4B-IN-B3) is a novel and potent inhibitor of the Histone lysine demethylase KDM4 with an IC50 of 10 nM. NCGC00244536 inhibits the in vivo growth of tumors derived from PC3 cells and ex vivo human PCa explants. Histone lysine demethylase KDM4/JMJD2s are overexpressed in many human tumors including prostate cancer (PCa). NCGC00244536 repressed the transcription of both AR and BMYB-regulated genes. NCGC00244536 is highly selective for a variety of cancer cell lines including PC3 cells that lack AR. NCGC00244536 inhibited the in vivo growth of tumors derived from PC3 cells and ex vivo human PCa explants. A novel mechanism by which KDM4B activates the transcription of Polo-like kinase 1 (PLK1) was identified. NCGC00244536 blocked the binding of KDM4B to the PLK1 promoter. Our studies suggest a potential mechanism-based therapeutic strategy for PCa and tumors with elevated KDM4B/PLK1 expression.
| 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].
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| ln Vivo |
Tumor growth was markedly inhibited by treatment with NCGC00244536, and the animals showed no significant toxicity and appeared normal. Histological evidence unequivocally showed that tumors treated with NCGC00244536 were highly cellular, distinct, and fibrous [1].
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| References |
[1]. Duan L, et al. KDM4/JMJD2 Histone Demethylase Inhibitors Block Prostate Tumor Growth by Suppressing the Expression of AR and BMYB-Regulated Genes. Chem Biol. 2015 Sep 17;22(9):1185-96
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| Molecular Formula |
C25H22N2O2
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| Molecular Weight |
382.46
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| CAS # |
2003260-55-5
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| SMILES |
O=C(NCCCC1=CC=CC=C1)C2=CC=CC(C3=CC(O)=C4N=CC=CC4=C3)=C2
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| 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) |
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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 | 13.0733 mL | 26.1465 mL | |
| 5 mM | 0.5229 mL | 2.6147 mL | 5.2293 mL | |
| 10 mM | 0.2615 mL | 1.3073 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.
Novel KDM4 inhibitors selectively inhibit prostate tumor growth.Chem Biol.2015 Sep 17;22(9):1185-96. |
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KDM4 siRNA and inhibitors inhibited DNA replication of PCa cells.Chem Biol.2015 Sep 17;22(9):1185-96. |
 Cell cycle-dependent PLK1 expression requires KDM4 activity.Chem Biol.2015 Sep 17;22(9):1185-96. |
Compound B3 inhibits AR and critical cell cycle genes inex vivosolid human prostate tumors and growth of PC3 xenograft tumorin vivo.Chem Biol.2015 Sep 17;22(9):1185-96. |
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Inhibition of KDM4B by either siRNA or inhibitors down-regulated the expressions of cell cycle genes including PLK1.
KDM4B interacts with BMYB and activates BMYB-targeted PLK1 transcription.Chem Biol.2015 Sep 17;22(9):1185-96. |
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