Identification of Natural Compound Radicicol as a Potent FTO Inhibitor

Wang, Ruiyong; Han, Zhifu; Liu, Bingjie; Zhou, Bin; Wang, Ning; Jiang, Qingwei; Qiao, Yan; Song, Chuanjun; Chai, Jijie; Chang, Junbiao

doi:10.1021/acs.molpharmaceut.8b00522

Cited by 65 publications

(58 citation statements)

References 45 publications

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“…Our previous results showed that radicicol, CHTB, and N‐CDPCB can bind to FTO. It was found that CHTB‐FTO complex has the highest binding affinity followed by 1d, radicicol, and N‐CDPCB as shown in Table .…”

Section: Resultsmentioning

confidence: 96%

“…Enzymatic activity assays in vitro were carried out as described previously . Analogues at varying concentrations (3.0 μM, 6.0 μM, 10.0 μM, 15.0 μM, 30.0 μM, 50.0 μM, 100.0 μM, and 150.0 μM) were used in the assays.…”

Section: Methodsmentioning

confidence: 99%

“…Analogues at varying concentrations (3.0 μM, 6.0 μM, 10.0 μM, 15.0 μM, 30.0 μM, 50.0 μM, 100.0 μM, and 150.0 μM) were used in the assays. The solutions were analyzed by LC‐MS as described in previous publications . The mode was Liquid chromatography‐mass spectrometry (LC‐MS) Multiple Reaction Monitoring (MRM).…”

Section: Methodsmentioning

confidence: 99%

“…The mode was Liquid chromatography‐mass spectrometry (LC‐MS) Multiple Reaction Monitoring (MRM). The drug concentration providing 50% inhibition (IC 50 ) was obtained from dose‐response curves fitted with GraphPad Prism 6.0 as described previously …”

Section: Methodsmentioning

confidence: 99%

“…FTO inhibitors have been reported, such as rhein, α‐ketoglutarate (αKG) analogues, meclofenamic acid, radicicol, and so on . Previous work in our group showed that 4‐chloro‐6‐(6'‐chloro‐7'‐hydroxy‐2',4',4,‐trimethyl‐chroman‐2'‐yl)benzene‐1,3‐diol (CHTB) and N‐(5‐chloro‐2,4‐dihydroxyphenyl)‐1‐phenylcyclobutanecarboxamide (N‐CDPCB) are inhibitors of FTO .…”

Section: Introductionmentioning

confidence: 99%

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The role of chlorine atom on the binding between 2‐phenyl‐1H‐benzimidazole analogues and fat mass and obesity‐associated protein

Wang

Han

et al. 2018

J of Molecular Recognition

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In this work, nine 2‐phenyl‐1H‐benzimidazole structural analogues were screened for potential inhibitor of the fat mass and obesity‐associated protein (FTO) by isothermal titration calorimetry (ITC). The results show that the binding between 6‐chloro‐2‐phenyl‐1H‐benzimidazole (1d) and FTO was dominated by entropy. Results of enzymatic activity assays provided an IC50 value of 24.65 μM for 1d. Our previous results and comparison of nine structural analogues indicated that the chlorine atom was crucial for the binding of small molecules with FTO. The identification of novel small molecules may provide information for the design of FTO inhibitors and the treatment of leukemia.

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Section: Resultsmentioning

confidence: 96%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The role of chlorine atom on the binding between 2‐phenyl‐1H‐benzimidazole analogues and fat mass and obesity‐associated protein

Wang

Han

et al. 2018

J of Molecular Recognition

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Bovine β‐casein binding studies of a Schiff base ligand: fluorescence and circular dichroism approaches

2020

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In this study, a Schiff base derived from a heterocyclic moiety was synthesized and characterized. The in vitro binding behaviour of this ligand with β‐casein (β‐CN) was investigated using biophysical techniques. For evaluation, thermodynamics variables of interactions between the Schiff base ligand and β‐CN, such as fluorescence at different temperatures, were measured. The results showed that the Schiff base ligand possessed considerable associated binding to β‐CN and that the procedure was enthalpy driven. The β‐CN conformation was also changed to give a further unfolded structure. Fluorescence resonance energy transfer was used to estimate the interval between donor (β‐CN) and acceptor (Schiff base ligand). All these experimental results proposed that β‐CN might act as carrier protein for the Schiff base ligand to deliver it to the target molecules.

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Anti‐cancer effect of entacaponeon esophageal cancer cells via apoptosis induction and cell cycle modulation

et al. 2022

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Background: Esophageal cancer (EC) is the sixth leading cause of cancer-related death, despite many advances in treatment, the survival of patients still remains poor.In recent years, the N6-methyladenosine (m6A) has been introduced as one of the most important modifications at the epitranscriptome level, with an important role in the mRNA regulation in various diseases, such as cancers. The m6A is regulated by different factors, including FTO as a demethylase. The m6A modification, especially through FTO overexpression has an oncogenic role in different cancer types such as EC. Recent studies showed that entacapone, a catechol-o-methyl transferase (COMT) inhibitor currently applied for Parkinson's disease, can inhibit FTO enzyme.Aims: In this study, we aimed to investigate the effect of entacapone as an FTO inhibitor on the m6A level and also apoptosis and cell cycle response in KYSE-30 and YM-1 of esophageal squamous cancer cell (ESCC) lines.Methods: Cell toxicity and IC50 of entacapone were evaluated using The MTT assay in YM-1 and KYSE-30 cells. Cells were treated into two groups: DMSO (control) and entacapone (mean IC 50 ). Total RNA was extracted, and m6A levels were measured via the ELISA method. Subsequently, the apoptosis and cell cycle dys-regulation were detected by annexin-V-FITC/PI staining and PI staining via flow cytometry.Results: Entacapone has the cytotoxicity effect on both esophageal cancer cell lines compared to normal PBMC cells. As well, entacapone treatment (140 μM) can induce apoptosis (KYSE-30: 50%. YM-1:22.6%) and has a modulatory effect on cell cycle progression in both YM-1 and KYSE-30 cells (p-value<.05). However, no significant difference in the m6A concentration was observed. Conclusion:Our findings suggested that entacapone has the inhibitory effect on ESCC cell lines through induction of the apoptosis and modulation of the cell cycle without toxicity on the normal PBMC.

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Identification of Natural Compound Radicicol as a Potent FTO Inhibitor

Cited by 65 publications

References 45 publications

The role of chlorine atom on the binding between 2‐phenyl‐1H‐benzimidazole analogues and fat mass and obesity‐associated protein

The role of chlorine atom on the binding between 2‐phenyl‐1H‐benzimidazole analogues and fat mass and obesity‐associated protein

Bovine β‐casein binding studies of a Schiff base ligand: fluorescence and circular dichroism approaches

Anti‐cancer effect of entacaponeon esophageal cancer cells via apoptosis induction and cell cycle modulation

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