Abstract:
:Polycomb repressive complex 2 (PRC2) is an attractive drug target for anti-cancer treatment. Among the three core subunits (EZH2, EED and SUZ12) of PRC2, EZH2 is the catalytic subunit that methylates histone H3 lysine 27 (H3K27), while EED is the regulatory subunit. Besides the small-molecule inhibitors of EZH2, those targeting the protein-protein interaction (PPI) between EZH2 and EED have also been reported. Here, for the first time, we have identified the key residues that contributed most to the EED-EZH2 binding affinity by molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) calculations based on the 200 ns molecular dynamics simulation. Moreover, we report the identification of two novel and potent small-molecule inhibitors (35 and 49) of EZH2-EED interaction (bottom interaction surface) by virtual screening and biological evaluations. Binding modes of the two identified molecules with EED were probed by molecular docking. Additionally, 35 and 49 displayed cellular antiproliferative activity against diffuse large B-cell lymphoma (DLBCL) cancer cell line Toledo whose cell growth was driven by aberrant PRC2 activity. Our findings have provided structural insights for the design of novel EZH2-EED interaction inhibitors to regulate the activity of PRC2 complex.
journal_name
Chem Pharm Bull (Tokyo)journal_title
Chemical & pharmaceutical bulletinauthors
Zhu K,Du D,Yang R,Tao H,Zhang Hdoi
10.1248/cpb.c19-00550subject
Has Abstractpub_date
2020-01-01 00:00:00pages
58-63issue
1eissn
0009-2363issn
1347-5223journal_volume
68pub_type
杂志文章abstract::Two new monodesmosidic triterpene saponins were isolated from the roots of Gypsophila oldhamiana (Caryophyllaceae). Their structures were elucidated on the basis of spectral data to be quillaic acid, alpha-L-arabinopyranosyl-(1-->4)-alpha-L-arabinopyranosyl-(1-->3)-beta-D-xylopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.54.1200
更新日期:2006-08-01 00:00:00
abstract::The effect of regucalcin, a calcium-binding protein isolated from rat liver cytosol, on cytosolic Ca2+/calmodulin-dependent protein kinase activity was investigated. The increase in cytosolic Ca2+/calmodulin-dependent protein kinase activity with passage of incubation time was clearly prevented by the presence of regu...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.38.2216
更新日期:1990-08-01 00:00:00
abstract::The dissolution of oval soft gelatin capsules containing 5 mg of nifedipine dissolved in a water soluble vehicle was evaluated by the rotating dialysis cell (RDC) method and the paddle (PD) method as described in the Japanese Pharmacopoiea (JP) XI. The dissolution pattern of nifedipine obtained by the PD method was li...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.42.333
更新日期:1994-02-01 00:00:00
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
doi:10.1248/cpb.c19-00820
更新日期:2020-01-01 00:00:00
abstract::This paper introduces a new delivery system for rapid and controlled drug release. Mixture of hydrophilic, (poly vinyl alcohol, PVA, and randomly methylated beta-cyclodextrin, RM beta-CD), and hydrophobic (poly D,L-lactide, PLA, and poly D,L-lactide-co-glycoside, PLGA) polymers were electrospun to make a multi-layered...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.58.143
更新日期:2010-02-01 00:00:00
abstract::This paper describes syntheses and doxorubicin-inclusion abilities of beta-cyclodextrin (CyD) derivatives with a hydroquinone alpha-glycoside residue attached at the primary side. The hydroquinone glycoside having an alpha-D-glucosidic or 2-acetamido-2-deoxy-alpha-D-glucosidic linkage became a useful component for pro...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.57.74
更新日期:2009-01-01 00:00:00
abstract::The metabolic pathway of butylated hydroxytoluene (BHT) to the ring-oxygenated metabolites 2,6-di-tert-butylhydroquinone (BHQ) and 2,6-di-tert-butyl-p-benzoquinone (BBQ) was examined in rats. After intraperitoneal administration of 3,5-di-tert-butyl-4-hydroxybenzoic acid (BHT-acid), which had been regarded as one of t...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.39.512
更新日期:1991-02-01 00:00:00
abstract::Melt pelletization of lactose 450 M was carried out in an 8-l high shear mixer using PEG 3000 as the meltable binder. The pore size and size distribution of the melt pellets were determined using mercury intrusion porosimetry. The pore size distribution of melt pellets was found to be bimodal. With a higher binder con...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.48.1639
更新日期:2000-11-01 00:00:00
abstract::A series of 5-(pyridin-4-yl)-N-substituted-1,3,4-oxadiazol-2-amines (3a-d), 5-(pyridin-4-yl)-N-substituted-1,3,4-thiadiazol-2-amines (4a-d) and 5-(pyridin-4-yl)-4-substituted-1,2,4-triazole-3-thiones (5a-d) were obtained by the cyclization of hydrazinecarbothioamide derivatives 2a-d derived from isonicotinic acid hydr...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.c15-00059
更新日期:2015-01-01 00:00:00
abstract::In order to gain an understanding of protein binding of sulfadimethoxine (SDM) and its major metabolite, N4-acetylsulfadimethoxine (N4-AcSDM), the binding of SDM and N4-AcSDM to human and rabbit serum albumin (HSA and RSA) was investigated using circular dichroism (CD), fluorescence and dialysis techniques. The CD spe...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.37.498
更新日期:1989-02-01 00:00:00
abstract::A new class of mono and bis heterocycles-styrylsulfonylmethyl 1,3,4-oxadiazoles, pyrazolyl/isoxazolyl-1,3,4-oxadiazoles were prepared and studied their antioxidant activity. The compound methyl substituted 2-(p-methylphenylamino-sulfonylmethyl)-5-[Z-(p-methylstyrylsulfonylmethyl)]-1,3,4-oxadiazole displayed slightly h...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.c13-00652
更新日期:2013-01-01 00:00:00
abstract::In the pharmaceutical preparation of a controlled release drug, it is very important and necessary to understand the entire release properties. As the first step, the dissolution test under various conditions is selected for the in vitro test, and usually the results are analyzed following Drug Approval and Licensing ...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.54.1091
更新日期:2006-08-01 00:00:00
abstract::A nondestructive, efficient, and rapid method for quantitative analysis of two bioactive components (salidroside and p-tyrosol) in Rhodiola crenulata, a traditional Tibetan medicine, by Fourier transform near-infrared (FT-NIR) spectroscopy was developed. Near-infrared diffuse reflectance spectra in the range of 4000 t...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.c15-00558
更新日期:2016-01-01 00:00:00
abstract::A new cardenolide diglycoside (1) was isolated from Nerium oleander together with ten known cardenolide diglycosides 2-11. The structure of compound 1 was established on the basis of their spectroscopic data. The in vitro anti-inflammatory activity of compounds 1-11 was examined on the basis of inhibitory activity aga...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.59.371
更新日期:2011-01-01 00:00:00
abstract::Two new diarylheptanoids, designated muricarpones A and B, together with three known diarylheptanoids, 1,7-di-(3',4'-dihydroxyphenyl)-4-hepten-3-one, 1-(3',4'-dihydroxyphenyl)-7-(4''-hydroxyphenyl)-4-hepten-3-one, and 1,7-bis(p-hydroxyphenyl)-4-hepten-3-one, were isolated from the rhizomes of Amomum muricarpum ELMER (...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.54.139
更新日期:2006-01-01 00:00:00
abstract::The intercalation reaction of diclofenac sodium (DFS) with layered inorganic compounds, gamma-titanium phosphate (gamma-TiP), proton type titanium oxide (H-TiO2) and sodium type synthetic mica (Na-TSM), was examined on. The direct reaction of DFS in ethanol-water mixed solvent resulted in the large amount accommodatio...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.53.1396
更新日期:2005-11-01 00:00:00
abstract::In order to understand the relation between the electronic structure of neurotransmitters and the brain, a model of the brain based on absolute hardness (eta) and absolute electronegativity (chi) is described. It was found that the coordinate r(chi, eta) of electronic structures of neurotransmitters obtained using the...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.52.517
更新日期:2004-05-01 00:00:00
abstract::Four new compounds 1-4 were obtained from an oxidative coupling reaction of (E)-isorhapontigenin using FeCl(3) as oxidant. Their structures and stereochemistry were determined on the basis of spectroscopic evidence [UV, IR, MS, (1)H-, (13)C-NMR, NOE and 2D NMR], and their possible formation mechanisms were also discus...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.52.238
更新日期:2004-02-01 00:00:00
abstract::The interaction between FSM-16 and flurbiprofen (FBP) in the mesopores of FSM-16 was investigated by using three types of FSM-16 with different pore diameters, i.e., FSM-16(Oc), FSM-16(Do) and FSM-16(Doc) (pore diameters 16.0, 21.6, 45.0 A, respectively). Solid dispersions of 30% FBP-70% FSM-16 were prepared by solven...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.53.974
更新日期:2005-08-01 00:00:00
abstract::The anti-anginal drug Ranolazine, a partial fatty acid oxidation (pFOX) inhibitor, is thought to modulate the metabolism during myocardial ischemia by activating pyruvate dehydrogenase activity to promote glucose oxidation. Ranolazine and its five principal metabolites: CVT-2512, CVT-2513, CVT-2514, CVT-2738 and CVT-4...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.57.1218
更新日期:2009-11-01 00:00:00
abstract::A new gluco indole alkaloid, 3,4-dehydro-5-carboxystrictosidine, was obtained from Peruvian Uña de Gato (Cat's Claw, original plant: Uncaria tomentosa) together with two known gluco indole alkaloids. This compound was the first example of isolation of a gluco monoterpenoid indole alkaloid having a 3,4-dihydro-beta-car...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.48.1410
更新日期:2000-10-01 00:00:00
abstract::Colon-specific drug delivery systems (CDDS) can improve the bioavailability of drug through the oral route. A novel formulation for oral administration using pH-enzyme Di-dependent chitosan mcirospheres (MS) and 5-Fu as a model drug has been investigated for colon-specific drug delivery by the emulsification/chemical ...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.56.963
更新日期:2008-07-01 00:00:00
abstract::An examination was made on the effect of fumaric acid on an experimental systemic candidiasis. Male ICR mice were innoculated into the tail veins with 10(6) yeast cells of Candida albicans and treated with daily intraperitoneal injections of fumaric acid at the dose of 40 mg/kg/d. The results indicated that the admini...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.39.3077
更新日期:1991-11-01 00:00:00
abstract::A new flavonol triglycoside, isorhamnetin 3-O-beta-D-xylopyranosyl-(1"-->3)-alpha-L-rhamnopyranosyl-(1'''-->6")-beta-D-galactopyranoside, has been isolated from the leaves of Hammada scoparia together with two known compounds, isorhamnetin 3-O-beta-D-apiofuranosyl-(1'''-->2")[alpha-L-rhamnopyranosyl-(1"-->6")]-beta-D-...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.50.1268
更新日期:2002-09-01 00:00:00
abstract::A novel series of N-arylpiperazine-1-carboxamide derivatives was synthesized and their androgen receptor (AR) antagonist activities and in vivo antiandrogenic properties were evaluated. Reporter assays indicated that trans-2,5-dimethylpiperazine derivatives are potent AR antagonists, and in this series trans-N-4-[4-cy...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.53.402
更新日期:2005-04-01 00:00:00
abstract::As part of the search for new topical antiinflammatory agents, various 21-substituted corticosteroids having sulfur-containing moieties were prepared and tested for vasoconstrictive activity in humans. A structure-activity relationship study revealed that substitution of the 21-hydroxy group with a lower alkyl-thio gr...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.37.1795
更新日期:1989-07-01 00:00:00
abstract::Three new carotenoids with a 3-methoxy-5-keto-5,6-seco-4,6-cyclo-beta end group (1-3) have been isolated from the seeds of Pittosporum tobira. Their structures were elucidated by detailed analyses of nuclear magnetic resonance and UV data. ...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.49.985
更新日期:2001-08-01 00:00:00
abstract::In the search for a practical route to ornithine bisurethane derivatives useful for peptide synthesis, we elaborated the simple and efficient (86% yield) synthesis of N(epsilon)-tert-butoxycarbonyl-L-ornithine copper(II) complex (1). This served as substrate for obtaining N(epsilon)-tert-butoxycarbonyl-L-ornithine (2)...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.49.1189
更新日期:2001-09-01 00:00:00
abstract::2,8-Dimethyl-1-oxa-8-azaspiro[4,5]decan-3-one (17), designed by incorporating the tetrahydrofuran ring moiety of muscarone into an 8-azaspiro[4,5]decane skeleton, and related 1-oxa-8-azaspiro[4.5]decanes were synthesized and assessed as M1 muscarinic agonists for the symptomatic treatment of dementia of Alzheimer's ty...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.43.842
更新日期:1995-05-01 00:00:00
abstract::Arginine-vasopressin (AVP) was acylated with various acyl azides (2a-j) in pH 9.1 buffer to give AVP derivatives (11a-j) modified at the tyrosine side chain with a carbohydrate via a spacer arm. Glycoconjugates of AVP modified at the N-terminal amide (12a-e) were also synthesized from AVP and carboxylic acids (3a-e) u...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.46.1530
更新日期:1998-10-01 00:00:00