ML324

製品コードS7296 バッチS729602

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C21H23N3O2
分子量 349.43 CAS No. 1222800-79-4
Solubility (25°C)* 体外 DMSO 43 mg/mL warmed with 50ºC water bath (123.05 mM)
Ethanol 6 mg/mL warmed with 50ºC water bath (17.17 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 ML324 is a selective inhibitor of jumonji histone demethylase (JMJD2) with IC50 of 920 nM.
in vitro ML324 exhibits good Caco-2 cell permeability, and possesses excellent microsomal stability in the presence of both mouse and rat liver microsomes. ML324 demonstrates potent anti-viral activity against both herpes simplex virus (HSV) and human cytomegalovirus (hCMV) infection by inhibiting viral IE gene expression. [1]
in vivo In a mouse ganglia explant model of latently infected mice, ML324 suppresses the formation of HSV plaques, and blocks HSV-1 reactivation. [1]

プロトコル(参考用のみ)

キナーゼアッセイ AlphaScreen Assay
Inhibition of JMJD2E is assessed using the histone demethylase AlphaScreen assay. This assay uses a biotinylated peptide substrate and relies on detection of the product methyl mark using a specific antibody coupled to protein-A acceptor beads and a Steptavidin donor bead to capture the peptide. The assay is performed in 384-well plate format using white proxiplates. All steps are carried out in assay buffer (50 mM HEPES pH 7.5, 0.1% (w/v) BSA and 0.01 % (v/v) Tween-20). FAS is dissolved fresh each day in 20 mM HCl to a concentration of 400 mM and diluted to 1 mM in deionized water. All other components are dissolved fresh each day in deionized water. For IC50 determinations, 4.9 μL of assay buffer containing JMJD2E enzyme (2 nM final concentration) is transferred to wells of a 384-well proxiplate. Titrations of compound (0.1 μL) are transferred to each well and the enzyme is allowed to pre-incubate for 15 min with compound (final concentration of DMSO is 1%). The enzyme reaction is initiated by addition of 5 μL of a substrate mix consisting of 2-OG (10 μM final concentration), FAS (1 μM final concentration), L-Ascorbic Acid (100 μM final concentration) and biotinylated peptide substrate (30 nM final concentration) and the reaction allowed to proceed for 20 min at room temperature. The enzyme reaction is stopped by addition of 5 μL of EDTA (7.5 mM final concentration in assay buffer). Streptavidin Donor beads (0.08 mg/mL) and Protein-A conjugated acceptor beads (0.08 mg/mL) are pre-incubated for 1 hr with anti-H3-K9Me2 antibody (0.2 μg/mL, Abcam). The presence of biotin-H3-product is detected by addition of 5 μL of the pre-incubated AlphaScreen beads (final concentrations of 0.02 mg/mL with respect to acceptor and donor beads). Detection is allowed to proceed for 1 hr at room temperature and the assay plates are read on a BMG Pherastar FS plate reader. Data are normalized to the no enzyme control and the IC50 is determined from the nonlinear regression curve fit using GraphPad Prism 5.
動物実験 動物モデル Mouse ganglia explant model of latently infected mice
投薬量 ~50 μM
投与方法 --

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Methionine restriction promotes cGAS activation and chromatin untethering through demethylation to enhance antitumor immunity [ Cancer Cell, 2023, 41(6):1118-1133.e12] PubMed: 37267951
Priming therapy by targeting enhancer-initiated pathways in patient-derived pancreatic cancer cells [ EBioMedicine, 2023, 92:104602] PubMed: 37148583
Evaluation of Histone Demethylase Inhibitor ML324 and Acyclovir against Cyprinid herpesvirus 3 Infection [ Viruses, 2023, 15(1)163] PubMed: 36680202
Inhibition of histone demethylase KDM4 by ML324 induces apoptosis through the unfolded protein response and Bim upregulation in hepatocellular carcinoma cells [ Chem Biol Interact, 2022, 353:109806] PubMed: 34999051
Inhibitors of Jumonji C domain-containing histone lysine demethylases overcome cisplatin and paclitaxel resistance in non-small cell lung cancer through APC/Cdh1-dependent degradation of CtIP and PAF15 [ Cancer Biol Ther, 2022, 23(1):65-75] PubMed: 35100078
PDI inhibitor LTI6426 enhances panobinostat efficacy in preclinical models of multiple myeloma [ Cancer Chemother Pharmacol, 2022, 89(5):643-653] PubMed: 35381875
Essential role of the histone lysine demethylase KDM4A in the biology of malignant pleural mesothelioma (MPM) [ Br J Cancer, 2021, 10.1038/s41416-021-01441-7] PubMed: 34088988
Disruption of the Plasmodium falciparum Life Cycle through Transcriptional Reprogramming by Inhibitors of Jumonji Demethylases. [ ACS Infect Dis, 2020, 8;6(5):1058-1075] PubMed: 32272012
JMJD2 promotes acquired cisplatin resistance in non-small cell lung carcinoma cells. [ Oncogene, 2019, 38(28):5643-5657] PubMed: 30967636
Epigenetic Reprogramming with Antisense Oligonucleotides Enhances the Effectiveness of Androgen Receptor Inhibition in Castration-Resistant Prostate Cancer [ Cancer Res, 2018, 78(20):5731-5740] PubMed: 30135193

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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