A novel tamoxifen derivative, ridaifen-F, is a nonpeptidic small-molecule proteasome inhibitor

Hasegawa, Makoto; Yasuda, Yo; Tanaka, Makoto; Nakata, Kenya; Umeda, Eri; Wang, Yanwen; Watanabe, Chihiro; Uetake, Shoko; Kunoh, Tatsuki; Shionyu, Masafumi; Sasaki, Ryuzo; Shiina, Isamu; Mizukami, Tamio

doi:10.1016/j.ejmech.2013.11.009

Cited by 18 publications

(10 citation statements)

References 45 publications

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“…Non-competitive inhibition of 20S proteasome has been observed for the PA activity of quinoline 5-AHQ (Fig. 1), 3f and for the ChT-L activity of oxadiazoles, 9a tamoxifen derivatives 17 or peptide derivatives. 16a,18 Fig.…”

Section: Introductionmentioning

confidence: 87%

“…Such a competitive inhibition mechanism has been reported mainly for the ChT-L activity of non-covalent peptide derivatives 16 and also for the PA activity of tamoxifen derivatives. 17 The PA activity was inhibited non-competitively. 15 Inhibitor 6e binds with an equal affinity to the enzyme alone or the enzyme in complex with the substrate (K i = K' i = 13.2 ± 0.6 µM).…”

Section: Introductionmentioning

confidence: 97%

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Synthesis of novel 3-(quinazol-2-yl)-quinolines via SNAr and aluminum chloride-induced (hetero) arylation reactions and biological evaluation as proteasome inhibitors

Boualia

Debache

Boulcina

et al. 2020

Tetrahedron Letters

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Section: Introductionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 97%

Synthesis of novel 3-(quinazol-2-yl)-quinolines via SNAr and aluminum chloride-induced (hetero) arylation reactions and biological evaluation as proteasome inhibitors

Boualia

Debache

Boulcina

et al. 2020

Tetrahedron Letters

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“…Later, in 2014, in order to analyze the binding mode of ridaifen-F (a nonpeptidic small-molecule proteasome inhibitor based on tamoxifen) derivatives of the proteasome, docking studies were performed [144]. The crystallographic structure of the yeast 20S proteasome complexed with fellutamide B (PDB ID: 3D29) was used for docking calculations of the ridaifen-F derivatives.…”

Section: Computer-aided Drug Designmentioning

confidence: 99%

“…The possible ligand-binding site was detected through application of Site Finder of MOE 2010.10, with the Connection Distance parameter set to 1.9 Å. Docking calculations were carried out using ASEDock. The output results suggested that the presence of two homopiperidine rings and the relationship between the homopiperidine rings and the side structures at the X position are important for the inhibition of the proteasome by ridaifen-F derivatives [144].…”

Section: Computer-aided Drug Designmentioning

confidence: 99%

Computational Approaches for the Discovery of Human Proteasome Inhibitors: An Overview

et al. 2016

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Abstract:Proteasome emerged as an important target in recent pharmacological research due to its pivotal role in degrading proteins in the cytoplasm and nucleus of eukaryotic cells, regulating a wide variety of cellular pathways, including cell growth and proliferation, apoptosis, DNA repair, transcription, immune response, and signaling processes. The last two decades witnessed intensive efforts to discover 20S proteasome inhibitors with significant chemical diversity and efficacy. To date, the US FDA approved to market three proteasome inhibitors: bortezomib, carfilzomib, and ixazomib. However new, safer and more efficient drugs are still required. Computer-aided drug discovery has long being used in drug discovery campaigns targeting the human proteasome. The aim of this review is to illustrate selected in silico methods like homology modeling, molecular docking, pharmacophore modeling, virtual screening, and combined methods that have been used in proteasome inhibitors discovery. Applications of these methods to proteasome inhibitors discovery will also be presented and discussed to raise improvements in this particular field.

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“…One of the RIDs, RID-G, could induce caspase-independent atypical cell death involving mitochondrial dysfunction in human neoplastic hematopoietic cell lines (5), and has been indicated to interact with calmodulin, heterogeneous nuclear ribonucleoproteins A2/B1 and zinc finger protein 638 during its cancer cell growth inhibition (6). RID-F may serve as a proteasome inhibitor, and inhibit chymotrypsin-like, trypsin-like and peptidylglutamyl peptide hydrolase activities (7,8). These findings suggest that the various mechanisms of RID-mediated cancer cell growth inhibition should be considered in future study.…”

Section: Introductionmentioning

confidence: 99%

Anti‑proliferative effect of ridaifen‑B on hepatoma cells

et al. 2018

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Abstract. Ridaifens (RIDs), a novel series of tamoxifen derivatives, exhibit a potent growth-inhibitory effect against numerous tumor cells regardless of the expression of estrogen receptors, and are thus promising candidates as novel anti-tumor drugs. RID-B is a first generation RIDs, and inhibits the proliferation of several tumor cell lines. However, the potentially growth inhibitory effect of RID-B against hepatoma cells, and the detailed mechanism underlying RID-B-mediated tumor cell death remain to be elucidated. The purpose of the current study was to evaluate the anti-proliferative effect of RID-B against hepatoma cells. The anti-proliferative effect of RID-B against human hepatoma Huh-7 cells was investigated by cell proliferation assay using WST-1 reagent, and caspase-3 activity was evaluated by using specific fluorescent substrate. In addition, DNA fragmentation in Huh-7 cells induced by RID-B was estimated by terminal deoxynucleotidyl transferase dUTP nick-end labelling assay, and binding of RID-B to double-stranded DNA was confirmed by mass spectrometry. RID-B (0.5, 1 and 2 µM) inhibited the growth of Huh-7 cells, seemingly dose-dependently, but did not inhibit the growth of normal primary rat hepatocytes in the same concentration range. Furthermore, the caspase-3 activity of Huh-7 cells was increased by RID-B (0.5 and 5 µM), and the anti-proliferative effect of RID-B (1 µM) on Huh-7 cells was partially suppressed by the addition of the caspase inhibitor, Z-VAD-FMK. Additionally, RID-B (10 µM) directly bound to double-stranded DNA, and the addition of DNA suppressed RID-B-mediated cell growth inhibition and DNA fragmentation in Huh-7 cells. From these data, it may be concluded that RID-B inhibited cell growth and induced apoptosis via activating caspase-3 and binding to DNA directly, leading to DNA fragmentation in hepatoma cells.

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A novel tamoxifen derivative, ridaifen-F, is a nonpeptidic small-molecule proteasome inhibitor

Cited by 18 publications

References 45 publications

Synthesis of novel 3-(quinazol-2-yl)-quinolines via SNAr and aluminum chloride-induced (hetero) arylation reactions and biological evaluation as proteasome inhibitors

Synthesis of novel 3-(quinazol-2-yl)-quinolines via SNAr and aluminum chloride-induced (hetero) arylation reactions and biological evaluation as proteasome inhibitors

Computational Approaches for the Discovery of Human Proteasome Inhibitors: An Overview

Anti‑proliferative effect of ridaifen‑B on hepatoma cells

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