Identification of new GATA4-small molecule inhibitors by structure-based virtual screening.


:Members of the GATA family of transcription factors are zinc finger proteins that were shown to play evolutionary conserved roles in cell differentiation and proliferation in different organisms. We hypothesized that by finding new molecules that inhibit their function to be crucial in future therapeutical interventions for various diseases. By virtual high throughput screening using a version of glide (Schrodinger®) program with both crystal and NMR structure of GATA C-terminal zinc finger, we identified new small molecular weight chemicals with lead-like properties. We used in vitro cell-based assays to show that these molecules selectively and efficiently inhibit GATA4 activity by inhibiting its interaction with the DNA. In addition we showed that these molecules can block the activation of downstream target genes by GATA4. Moreover these compounds can moderately enhanced a mouse model of myoblast differentiation into myotubes. This might be partially due to decreased GATA4/DNA interaction as shown by gel retardation assays. Further investigation is needed to reach selectivity and efficacy. Our study however do show that in silico screening combined with in vitro studies are efficient tools to unravel new molecules that interact with zinc finger proteins such as GATA4.


Bioorg Med Chem


El-Hachem N,Nemer G




Has Abstract


2011-03-01 00:00:00














  • Synthesis, structural characterization and cell death-inducing effect of novel palladium(II) and platinum(II) saccharinate complexes with 2-(hydroxymethyl)pyridine and 2-(2-hydroxyethyl)pyridine on cancer cells in vitro.

    abstract::Four palladium(II) and platinum(II) saccharinate (sac) complexes with 2-(hydroxymethyl)pyridine (2-hmpy) and 2-(2-hydroxyethyl)pyridine (2-hepy), namely trans-[Pd(2-hmpy)2(sac)2]·H2O (1), trans-[Pt(2-hmpy)2(sac)2]·3H2O (2), trans-[Pd(2-hepy)2(sac)2] (3) and trans-[Pt(2-hepy)2(sac)2] (4), have been synthesized and char...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Ari F,Aztopal N,Icsel C,Yilmaz VT,Guney E,Buyukgungor O,Ulukaya E

    更新日期:2013-11-01 00:00:00

  • Synthesis and characterization of mitoQ and idebenone analogues as mediators of oxygen consumption in mitochondria.

    abstract::Analogues of mitoQ and idebenone were synthesized to define the structural elements that support oxygen consumption in the mitochondrial respiratory chain. Eight analogues were prepared and fully characterized, then evaluated for their ability to support oxygen consumption in the mitochondrial respiratory chain. While...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Duveau DY,Arce PM,Schoenfeld RA,Raghav N,Cortopassi GA,Hecht SM

    更新日期:2010-09-01 00:00:00

  • Studies on 6-chloro-5-(1-naphthyloxy)-2-(trifluoromethyl)-1H-benzimidazole/2-hydroxypropyl-β-cyclodextrin association: Characterization, molecular modeling studies, and in vivo anthelminthic activity.

    abstract::The purpose of this work is to study the molecular association that occurs between 2-hydroxypropyl-β-cyclodextrin (HPβCD) and 6-chloro-5-(1-naphthyloxy)-2-(trifluoromethyl)-1H-benzimidazole (RCB20), an antiparasitic compound recently found by our research group, with poor aqueous solubility. The complex stability cons...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Rojas-Aguirre Y,Yépez-Mulia L,Castillo I,López-Vallejo F,Soria-Arteche O,Hernández-Campos A,Castillo R,Hernández-Luis F

    更新日期:2011-01-15 00:00:00

  • Isolation, structure, and antibacterial activity of thiazomycin A, a potent thiazolyl peptide antibiotic from Amycolatopsis fastidiosa.

    abstract::Thiazolyl peptides are a class of thiazole-rich macrocyclic potent antibacterial agents. Recently, we described thiazomycin, a new member of thiazolyl peptides, discovered by a thiazolyl peptide specific chemical screening. This method also allowed for the discovery of a new thiazolyl peptide, thiazomycin A, which car...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Zhang C,Zink DL,Ushio M,Burgess B,Onishi R,Masurekar P,Barrett JF,Singh SB

    更新日期:2008-10-01 00:00:00

  • Inhibition of the Ser-Thr phosphatases PP1 and PP2A by naturally occurring toxins.

    abstract::The okadaic acid class of naturally occurring toxins is a structurally diverse group of molecules that inhibit the protein phosphatases PP1 and PP2A. Studies providing information about the mode of binding between the toxins and the phosphatases contribute to an overall understanding of the signal transduction pathway...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章,评审


    authors: Sheppeck JE 2nd,Gauss CM,Chamberlin AR

    更新日期:1997-09-01 00:00:00

  • Antikinetoplastid antimitotic activity and metabolic stability of dinitroaniline sulfonamides and benzamides.

    abstract::N(1)-Phenyl-3,5-dinitro-N(4),N(4)-di-n-propylsulfanilamide (1) and N(1)-phenyl-3,5-dinitro-N(4),N(4)-di-n-butylsulfanilamide (2) show potent in vitro antimitotic activity against kinetoplastid parasites but display poor in vivo activity. Seventeen new dinitroaniline sulfonamide and eleven new benzamide analogs of thes...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: George TG,Johnsamuel J,Delfín DA,Yakovich A,Mukherjee M,Phelps MA,Dalton JT,Sackett DL,Kaiser M,Brun R,Werbovetz KA

    更新日期:2006-08-15 00:00:00

  • Bacterial biofilm formation inhibitory activity revealed for plant derived natural compounds.

    abstract::Use of herbal plant remedies to treat infectious diseases is a common practice in many countries in traditional and alternative medicine. However to date there are only few antimicrobial agents derived from botanics. Based on microbiological screening tests of crude plant extracts we identified four compounds derived ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Artini M,Papa R,Barbato G,Scoarughi GL,Cellini A,Morazzoni P,Bombardelli E,Selan L

    更新日期:2012-01-15 00:00:00

  • Preparation of yuanhuacine and relative daphne diterpene esters from Daphne genkwa and structure-activity relationship of potent inhibitory activity against DNA topoisomerase I.

    abstract::Two new daphne diterpene esters Yuanhuajine (2) and Yuanhuagine (4), together with three known daphne diterpene esters yuanhuacine (1), yuanhuadine (3), and yuanhuapine (5), were isolated and identified from Daphne genkwa, a traditional Chinese medicine. Their structures were elucidated by a combination of UV, IR, MS ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Zhang S,Li X,Zhang F,Yang P,Gao X,Song Q

    更新日期:2006-06-01 00:00:00

  • Design, synthesis, and biological evaluation of new phosphodiesterase type 4 inhibitors.

    abstract::The design, synthesis, and biological evaluation of new phosphodiesterase type 4 inhibitors, which possess new templates instead of a cyclohexane ring, are described. The mode of interaction with the enzyme is discussed based on the structure-activity relationship (SAR) data obtained for the synthesized inhibitors. Fu...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Ochiai H,Odagaki Y,Ohtani T,Ishida A,Kusumi K,Kishikawa K,Yamamoto S,Takeda H,Obata T,Kobayashi K,Nakai H,Toda M

    更新日期:2004-10-01 00:00:00

  • Database of bioactive ring systems with calculated properties and its use in bioisosteric design and scaffold hopping.

    abstract::A system for identification of bioisosteric scaffolds is presented. The system uses a database of over 7000 scaffolds extracted from bioactive molecules. Scaffolds in the database are characterized by their size, shape, pharmacophore features and several ADME descriptors. Also properties characterizing electron-donati...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Ertl P

    更新日期:2012-09-15 00:00:00

  • Discovery of novel thiourea derivatives as potent and selective beta3-adrenergic receptor agonists.

    abstract::In the search for potent and selective human beta3-adrenergic receptor (AR) agonists as potential drugs for the treatment of obesity and noninsulin-dependent (type II) diabetes, we prepared a novel series of phenoxypropanolamine derivatives containing the thiourea moiety and evaluated their biological activities at hu...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Maruyama T,Seki N,Onda K,Suzuki T,Kawazoe S,Hayakawa M,Matsui T,Takasu T,Ohta M

    更新日期:2009-08-01 00:00:00

  • Amides as bioisosteres of triazole-based geranylgeranyl diphosphate synthase inhibitors.

    abstract::Geranylgeranyl diphosphate synthase (GGDPS) inhibitors are of potential therapeutic interest as a consequence of their activity against the bone marrow cancer multiple myeloma. A series of bisphosphonates linked to an isoprenoid tail through an amide linkage has been prepared and tested for the ability to inhibit GGDP...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Goetz DB,Varney ML,Wiemer DF,Holstein SA

    更新日期:2020-08-15 00:00:00

  • 1-Methylpyridinium-4-(4-phenylmethanethiosulfonate) iodide, MTS-MPP+, a novel scanning cysteine accessibility method (SCAM) reagent for monoamine transporter studies.

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Gallardo-Godoy A,Torres-Altoro MI,White KJ,Barker EL,Nichols DE

    更新日期:2007-01-01 00:00:00

  • Design, synthesis and herbicidal activity of new iron chelating motifs for HPPD-inhibitors.

    abstract::HPPD (p-hydroxyphenylpyruvate dioxygenase) is a herbicidal target that all major companies active in plant protection research have worked on intensely in the last decade. Several modern herbicides with this mode of action have been introduced recently, or are currently in development. The activity of all commercializ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Witschel M

    更新日期:2009-06-15 00:00:00

  • Synthesis and biological evaluation of novel irreversible serine protease inhibitors using amino acid based sulfonyl fluorides as an electrophilic trap.

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Brouwer AJ,Ceylan T,Jonker AM,van der Linden T,Liskamp RM

    更新日期:2011-04-01 00:00:00

  • Variations in the C-unit of bedaquiline provides analogues with improved biology and pharmacology.

    abstract::Analogues of the anti-tuberculosis drug bedaquiline, bearing a 3,5-dimethoxy-4-pyridyl C-unit, retain high anti-bacterial potency yet exert less inhibition of the hERG potassium channel, in vitro, than the parent compound. Two of these analogues (TBAJ-587 and TBAJ-876) are now in preclinical development. The present s...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Sutherland HS,Tong AST,Choi PJ,Blaser A,Franzblau SG,Cooper CB,Upton AM,Lotlikar M,Denny WA,Palmer BD

    更新日期:2020-01-01 00:00:00

  • Discovery of novel quinoline-based mTOR inhibitors via introducing intra-molecular hydrogen bonding scaffold (iMHBS): The design, synthesis and biological evaluation.

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Ma X,Lv X,Qiu N,Yang B,He Q,Hu Y

    更新日期:2015-12-15 00:00:00

  • Synthesis of 3,6-diazabicyclo[3.1.1]heptanes as novel ligands for the opioid receptors.

    abstract::In an effort to improve diazabicycloalkane-based opioid receptor ligands, N-3(6)-arylpropenyl-N-6(3)-propionyl-3,6-diazabicyclo[3.1.1]heptanes (3A,Ba-i) were synthesized and their affinity and selectivity towards mu-, delta- and kappa-receptors were evaluated. The results of the current study revealed a number of comp...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Loriga G,Manca I,Murineddu G,Chelucci G,Villa S,Gessi S,Toma L,Cignarella G,Pinna GA

    更新日期:2006-02-01 00:00:00

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    abstract::In order to discover novel multidrug resistance (MDR) reversal agents for efficient cancer chemotherapy, the unsymmetrical curcumin mimics with various amide moieties (6-19) were synthesized and evaluated their MDR reversal activities in MDR cell line KBV20C. Among the tested compounds, 13, 16, and 17 showed potent MD...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Um Y,Cho S,Woo HB,Kim YK,Kim H,Ham J,Kim SN,Ahn CM,Lee S

    更新日期:2008-04-01 00:00:00

  • A topological substructural approach applied to the computational prediction of rodent carcinogenicity.

    abstract::The carcinogenic activity has been investigated by using a topological substructural molecular design approach (TOPS-MODE). A discriminant model was developed to predict the carcinogenic and noncarcinogenic activity on a data set of 189 compounds. The percentage of correct classification was 76.32%. The predictive pow...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Helguera AM,Cabrera Pérez MA,González MP,Ruiz RM,González Díaz H

    更新日期:2005-04-01 00:00:00

  • Synthesis of both enantiomers of hydroxypipecolic acid derivatives equivalent to 5-azapyranuronic acids and evaluation of their inhibitory activities against glycosidases.

    abstract::We have synthesized 3-hydroxy- and 3,4,5-trihydroxypipecolic acid derivatives corresponding to 5-aza derivatives of uronic acids and evaluated their inhibitory activities against various glycosidases including beta-glucuronidase. Compounds 4 and 5 were chosen as common intermediates for the synthesis of 3,4,5-trihydro...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Yoshimura Y,Ohara C,Imahori T,Saito Y,Kato A,Miyauchi S,Adachi I,Takahata H

    更新日期:2008-09-01 00:00:00

  • Studies on anti-HIV quinolones: new insights on the C-6 position.

    abstract::The 6-desfluoroquinolones which have been developed by our group represent a promising class of compounds for the treatment of HIV infection since they act on transcriptional regulation, a crucial step in the replication cycle that has not been clinically exploited, yet. Focussing attention on the N-1 and C-6 position...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Massari S,Daelemans D,Manfroni G,Sabatini S,Tabarrini O,Pannecouque C,Cecchetti V

    更新日期:2009-01-15 00:00:00

  • 5-demethylovalicin, as a methionine aminopeptidase-2 inhibitor produced by Chrysosporium.

    abstract::5-Demethylovalicin was isolated from the fermentation broth Chrysosporium lucknowense and the structure was identified by spectroscopic methods. 5-Demethylovalicin inhibited the recombinant human MetAP-2 (IC(50)=17.7 nM) and the growth of human umbilical vein endothelial cells (HUVEC; IC(50)=100 nM) in cell proliferat...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Son KH,Kwon JY,Jeong HW,Kim HK,Kim CJ,Chang YH,Choi JD,Kwon BM

    更新日期:2002-01-01 00:00:00

  • The 3-D QSAR study of anticancer 1-N-substituted imidazo- and pyrrolo-quinoline-4,9-dione derivatives by CoMFA and CoMSIA.

    abstract::The 3-D QSAR analysis with new imidazo- and pyrrolo-quinolinedione derivatives was conducted by Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA). When crossvalidation value (q(2)) is 0.844 at four components, the Pearson correlation coefficient (r(2)) of the C...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Suh ME,Kang MJ,Park SY

    更新日期:2001-11-01 00:00:00

  • Secondary assembly of bile salts mediated by beta-cyclodextrin-terbium(III) complex.

    abstract::A fluorescent cyclodextrin-Tb(III) complex is successfully synthesized and can include bile salts in its hydrophobic cavities. Therefore, it can efficiently induce the secondary assembly of small bile salt primary micelles to large micelle aggregates, and the aggregation process can be easily observed by transmission ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Liu Y,Zhang N,Chen Y,Chen GS

    更新日期:2006-10-01 00:00:00

  • Investigation of chalcones and benzochalcones as inhibitors of breast cancer resistance protein.

    abstract::Breast cancer resistance protein (BCRP/ABCG2) belongs to the ATP binding cassette family of transport proteins. BCRP has been found to confer multidrug resistance in cancer cells. A strategy to overcome resistance due to BCRP overexpression is the investigation of potent and specific BCRP inhibitors. The aim of the cu...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Juvale K,Pape VF,Wiese M

    更新日期:2012-01-01 00:00:00

  • Synthesis of hydrolysis-resistant pyridoxal 5'-phosphate analogs and their biochemical and X-ray crystallographic characterization with the pyridoxal phosphatase chronophin.

    abstract::A set of phosphonic acid derivatives (1-4) of pyridoxal 5'-phosphate (PLP) was synthesized and characterized biochemically using purified murine pyridoxal phosphatase (PDXP), also known as chronophin. The most promising compound 1 displayed primarily competitive PDXP inhibitory activity with an IC50 value of 79μM, whi...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Knobloch G,Jabari N,Stadlbauer S,Schindelin H,Köhn M,Gohla A

    更新日期:2015-06-15 00:00:00

  • 3'-Hydroxy-3,4'-dimethoxyflavone blocks tubulin polymerization and is a potent apoptotic inducer in human SK-MEL-1 melanoma cells.

    abstract::Flavonoids are naturally occurring polyphenolic compounds and are among the most promising anticancer agents. A series of flavonols and their 3-methyl ether derivatives were synthesized and assessed for cytotoxicity. It was found that 3'-hydroxy-3,4'-dimethoxyflavone (flavonoid 7a) displayed strong cytotoxicity agains...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Estévez-Sarmiento F,Said M,Brouard I,León F,García C,Quintana J,Estévez F

    更新日期:2017-11-01 00:00:00

  • Synthesis and biology of bis-xylosylated dihydroxynaphthalenes.

    abstract::The 10 analogous bis-xylosylated dihydroxynaphthalenes have been synthesized and their chemical and biological properties investigated. The yield of the xylosylation reactions can be correlated to the electrostatic potential, and thus to the nucleophilicity, for the oxygen atoms of the dihydroxynaphthalenes. The bis-x...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Johnsson R,Mani K,Ellervik U

    更新日期:2007-04-15 00:00:00

  • Novel 3,6-bis(imidazolidine)acridines as effective photosensitizers for photodynamic therapy.

    abstract::The photoeffect of new proflavine derivatives with DNA-binding and antitumour activities, 3,6-bis((1-alkyl-5-oxo-imidazolidin-2-yliden)imino)acridine hydrochlorides (AcrDIMs), was studied to evaluate them as potential photosensitizers for photodynamic antitumor therapy. EPR measurements showed that superoxide radical ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Cižeková L,Grolmusová A,Ipóthová Z,Barbieriková Z,Brezová V,Hunáková L,Imrich J,Janovec L,Dovinová I,Paulíková H

    更新日期:2014-09-01 00:00:00