Abstract:
:Enzymatic and post-translational modifications (PTMs) such as ubiquitination, acetylation, and methylation occur at lysine residues. The PTMs play critical roles in the regulation of the protein functions, and thus, various cellular processes. In addition, aberrations of the PTMs are associated with various diseases, such as cancer and neurodegenerative disorders. Therefore, we hypothesized that modulation of the PTMs and normalization of the PTM abnormalities could be useful as methods to control various cellular mechanisms and as a therapeutic strategy, respectively. To modulate the PTMs, we have focused on lysine-modifying enzymes and have pursued drug discovery researches on ubiquitination inducers, lysine deacetylase (KDAC) inhibitors, and lysine demethylase (KDM) inhibitors. For the identification of the modulators, we have used not only conventional drug design, such as structure-based drug design (SBDD) and ligand-based drug design (LBDD), but also "strategic chemistry approaches," such as drug design based on enzyme catalytic mechanism. As a result, we have identified several modulators which have pharmacological effects in animal models or in cellular studies. In this review, focusing on the drug design based on enzyme catalytic mechanism, our drug discovery researches have been discussed.
journal_name
Chem Pharm Bull (Tokyo)journal_title
Chemical & pharmaceutical bulletinauthors
Itoh Ydoi
10.1248/cpb.c19-00741subject
Has Abstractpub_date
2020-01-01 00:00:00pages
34-45issue
1eissn
0009-2363issn
1347-5223journal_volume
68pub_type
杂志文章,评审abstract::The aim of this study was to evaluate the effects of Magnolin (MGL) on inhibition of human breast cancer cells, and explore the underlying molecular mechanisms. The viability of the treated cells was assessed with the Cell Counting Kit-8 (CCK-8) assay, and the proliferation was analyzed in terms of EdU uptake, colony ...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
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更新日期:2020-01-01 00:00:00
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journal_title:Chemical & pharmaceutical bulletin
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journal_title:Chemical & pharmaceutical bulletin
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doi:10.1248/cpb.c17-00485
更新日期:2017-01-01 00:00:00
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journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.39.2207
更新日期:1991-09-01 00:00:00
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journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
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pub_type: 杂志文章
doi:10.1248/cpb.40.1016
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journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.56.1357
更新日期:2008-09-01 00:00:00
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journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.c14-00516
更新日期:2015-01-01 00:00:00
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journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.54.1535
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journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.40.575
更新日期:1992-03-01 00:00:00
abstract::Three new compounds were isolated from a MeOH extract of the leaves of Syzygium samarangense, one new cyanogenic glucoside, taxiphyllin 6'-O-gallate (1), one new megastigmane glucoside, actinidioionoside 6'-O-gallate (2), and one new sulfated flavonoid rhamnoside, myricetrin 2″-O-sulfate (3), together with 14 known co...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.c14-00352
更新日期:2014-01-01 00:00:00
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journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
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更新日期:1997-12-01 00:00:00
abstract::The structures of new neo-lignans, isoamericanol A (1) and americanol A (2) isolated from the seeds of Phytolacca americana have been elucidated on the basis of spectroscopic data and then confirmed by chemical correlation with the previously known isoamericanin A (3) and americanin A (4). Isoamericanol A, americanol ...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.40.252
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journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
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更新日期:1989-09-01 00:00:00
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journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
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更新日期:2005-12-01 00:00:00
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journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.50.1341
更新日期:2002-10-01 00:00:00
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journal_title:Chemical & pharmaceutical bulletin
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journal_title:Chemical & pharmaceutical bulletin
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journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
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journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.52.995
更新日期:2004-08-01 00:00:00
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journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.c14-00138
更新日期:2014-01-01 00:00:00
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journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
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更新日期:2006-07-01 00:00:00
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journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
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journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章,评审
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更新日期:2017-01-01 00:00:00
abstract::Three new glycosides, 7-deoxyloganic acid beta-D-glucopyranosyl ester (1), (3R)-hydrangenol 8,4'-di-O-beta-D-glucopyranoside (2), and (6R,7E,9R)-megastigma-4,7-dien-3-one 9,13-di-O-beta-D-glucopyranoside (3), have been isolated from the leaves of Hydrangea macrophylla subsp. serrata (THUNB.) MAKINO (Saxifragaceae). Th...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
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更新日期:2008-04-01 00:00:00
abstract::Two enkephalin-containing peptides, peptide E and dynorphin(1-24), were synthesized by conventional solution methods employing a new Trp derivative, Nin-(2,4,6-triisopropylphenylsulfonyl)tryptophan [Trp(Tps)]. All protecting groups employed including the Tps group were removed by treatment with 1 M trifluoromethanesul...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.37.2631
更新日期:1989-10-01 00:00:00
abstract::A new glycosyl inositolphosphoceramide-type ganglioside, CSP2, was obtained from the polar lipid fraction of the chloroform/methanol extract of the feather star Comanthina schlegeli together with a known same type of ganglioside CJP2. The structure of this ganglioside has been determined on the basis of chemical and s...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.55.1649
更新日期:2007-11-01 00:00:00
abstract::The compound tentatively named TL-1 was isolated from Talaromyces luteus as a metabolite having monoamine oxidase (MAO) inhibitory potency. TL-1 showed mixed-type inhibition of MAO in mouse liver when kynuramine was used as a substrate, and the IC50 was 6.6 microM. The inhibition constants (Ki) for MAO-A and -B in mou...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.37.206
更新日期:1989-01-01 00:00:00
abstract::We discovered that the reactivity of some conjugated and electron-deficient hydrocarbons was quite different in the presence of transition metal catalysts. In this review we report our development and applications of the highly selective palladium and nickel-catalyzed cycloaddition reactions of unsaturated hydrocarbon...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章,评审
doi:10.1248/cpb.53.1069
更新日期:2005-09-01 00:00:00