当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Discovery of new inhibitors of Cdc25B dual specificity phosphatases by structure-based virtual screening.

Discovery of new inhibitors of Cdc25B dual specificity phosphatases by structure-based virtual screening.

Abstract：

:Cell division cycle 25 (Cdc25) proteins are highly conserved dual specificity phosphatases that regulate cyclin-dependent kinases and represent attractive drug targets for anticancer therapies. To discover more potent and diverse inhibitors of Cdc25 biological activity, virtual screening was performed by docking 2.1 million compounds into the Cdc25B active site. An initial subset of top-ranked compounds was selected and assayed, and 15 were found to have enzyme inhibition activity at micromolar concentration. Among these, four structurally diverse inhibitors with a different inhibition profile were found to inhibit human MCF-7, PC-3, and K562 cancer cell proliferation and significantly affect the cell cycle progression. A subsequent hierarchical similarity search with the most active reversible Cdc25B inhibitor found led to the identification of an additional set of 19 ligands, three of which were confirmed as Cdc25B inhibitors with IC(50) values of 7.9, 4.2, and 9.9 μM, respectively.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Lavecchia A,Di Giovanni C,Pesapane A,Montuori N,Ragno P,Martucci NM,Masullo M,De Vendittis E,Novellino E

doi

10.1021/jm201624h

subject

Has Abstract

pub_date

2012-05-10 00:00:00

pages

4142-58

issue

9

eissn

0022-2623

issn

1520-4804

journal_volume

55

pub_type

杂志文章

相关文献

JOURNAL OF MEDICINAL CHEMISTRY文献大全
  • Further studies on the Dmt-Tic pharmacophore: hydrophobic substituents at the C-terminus endow delta antagonists to manifest mu agonism or mu antagonism.

    abstract：:Twenty N- and/or C-modified Dmt-Tic analogues yielded similar K(i) values with either [(3)H]DPDPE (delta(1) agonist) or [(3)H]N, N(Me)(2)-Dmt-Tic-OH (delta antagonist). N-Methylation enhanced delta antagonism while N-piperidine-1-yl, N-pyrrolidine-1-yl, and N-pyrrole-1-yl were detrimental. Dmt-Tic-X (X = -NHNH(2), -NH...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm990165m

    authors： Salvadori S,Guerrini R,Balboni G,Bianchi C,Bryant SD,Cooper PS,Lazarus LH

    更新日期：1999-12-02 00:00:00

  • Alkyl esters of 3-adenin-9-yl-2-hydroxypropanoic acid: a new class of broad-spectrum antiviral agents.

    abstract：:A new class of acyclic adenosine analogues is described which exhibit broad-spectrum antiviral activity and are apparently targeted at S-adenosyl-L-homocysteine hydrolase. The compounds are all alkyl (i.e., methyl, ethyl, 1-propyl, 2-propyl, 1-butyl, 2-butyl, 2-methylpropyl, tert-butyl, 1-pentyl, 3-methylbutyl, 1-octy...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00381a004

    authors： De Clercq E,Holý A

    更新日期：1985-03-01 00:00:00

  • Bispyridinium cyclophanes: novel templates for human choline kinase inhibitors.

    abstract：:The synthesis and biological activities of four novel bispyridinium cyclophanes as choline kinase (ChoK) inhibitors are presented. Their synthetic methodology has been optimized according to dilution, temperature, and reaction time and provides pure bispyridinium cyclophanes in high yields very easily. One of these cy...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm030792i

    authors： Conejo-García A,Campos JM,Sánchez-Martín RM,Gallo MA,Espinosa A

    更新日期：2003-08-14 00:00:00

  • Identification of structurally diverse growth hormone secretagogue agonists by virtual screening and structure-activity relationship analysis of 2-formylaminoacetamide derivatives.

    abstract：:Two molecules with known growth hormone secretagogue (GHS) agonist activity were used as templates to computationally screen approximately 80000 compounds. A total of 108 candidate compounds were selected, and five of them were found to be active in the low-micromolar range in both cell-based and direct binding assays...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm040103i

    authors： Shoda M,Harada T,Kogami Y,Tsujita R,Akashi H,Kouji H,Stahura FL,Xue L,Bajorath J

    更新日期：2004-08-12 00:00:00

  • Synthesis and evaluation of 2,3-dihydrobenzofuran analogues of the hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane: drug discrimination studies in rats.

    abstract：:Two analogues, 6-(2-aminopropyl)-5-methoxy-2,3-dihydrobenzofuran and 6-(2-aminopropyl)-5-methoxy-2-methyl-2,3-dihydrobenzofuran, of the hallucinogenic agent 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) were synthesized and tested in the two-lever drug discrimination paradigm. In rats trained to discriminate s...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00152a022

    authors： Nichols DE,Hoffman AJ,Oberlender RA,Riggs RM

    更新日期：1986-02-01 00:00:00

  • Isoform-selective substrates of nitric oxide synthase.

    abstract：:Because of the double-edged nature of NO, the development of isoform-selective NOS substrates is a highly desirable goal. Given the striking similarity in the heme active sites of the three NOS isoforms, it presents an challenging problem. Several N-aryl-N'-hydroxyguanidines have recently been shown as substrates that...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm0340703

    authors： Jia Q,Cai T,Huang M,Li H,Xian M,Poulos TL,Wang PG

    更新日期：2003-06-05 00:00:00

  • New Insights into Human 17β-Hydroxysteroid Dehydrogenase Type 14: First Crystal Structures in Complex with a Steroidal Ligand and with a Potent Nonsteroidal Inhibitor.

    abstract：:17β-HSD14 is a SDR enzyme able to oxidize estradiol and 5-androstenediol using NAD(+). We determined the crystal structure of this human enzyme as the holo form and as ternary complexes with estrone and with the first potent, nonsteroidal inhibitor. The structures reveal a conical, rather large and lipophilic binding ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.6b00293

    authors： Bertoletti N,Braun F,Lepage M,Möller G,Adamski J,Heine A,Klebe G,Marchais-Oberwinkler S

    更新日期：2016-07-28 00:00:00

  • The enantiomeric specificity of the antihypertensive activity of 1-(phenylthio)-2-aminopropane, a synthetic substrate analogue for dopamine beta-monooxygenase.

    abstract：:We have found that (R,S)-1-(phenylthio)-aminopropane (4a), a synthetic alternate substrate for the terminal enzyme of norepinephrine biosynthesis, dopamine beta-monooxygenase (DBM), is both an indirect sympathomimetic and a potent antihypertensive agent in spontaneously hypertensive rats. We demonstrate herein that th...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00107a031

    authors： Herman HH,Husain PA,Colbert JE,Schweri MM,Pollock SH,Fowler LC,May SW

    更新日期：1991-03-01 00:00:00

  • Conformation-function relationship of vitamin D: conformational analysis predicts potential side-chain structure.

    abstract：:In previous studies, we have grouped regions in space occupied by the vitamin D side chain into four: A, G, EA, and EG. We showed that the receptor (VDR) affinity of 1alpha,25-dihydroxyvitamin D3 derivatives increases, in terms of side-chain region, in the order EG, G, A, and EA. We called this the active space group ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm970761l

    authors： Yamada S,Yamamoto K,Masuno H,Ohta M

    更新日期：1998-04-23 00:00:00

  • 2-{3-[4-(Alkylsulfinyl)phenyl]-1-benzofuran-5-yl}-5-methyl-1,3,4-oxadiazole derivatives as novel inhibitors of glycogen synthase kinase-3beta with good brain permeability.

    abstract：:Glycogen synthase kinase 3beta (GSK-3beta) inhibition is expected to be a promising therapeutic approach for treating Alzheimer's disease. Previously we reported a series of 1,3,4-oxadiazole derivatives as potent and highly selective GSK-3beta inhibitors, however, the representative compounds 1a,b showed poor pharmaco...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm900647e

    authors： Saitoh M,Kunitomo J,Kimura E,Iwashita H,Uno Y,Onishi T,Uchiyama N,Kawamoto T,Tanaka T,Mol CD,Dougan DR,Textor GP,Snell GP,Takizawa M,Itoh F,Kori M

    更新日期：2009-10-22 00:00:00

  • Nitrogen bridgehead compounds. 44. New antiallergic 4H-pyrido[1,2-a]pyrimidin-4-ones. 4.

    abstract：:The weak antiallergic activity of 6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidine-3-carbox yli c acid (1) in the rat reaginic passive cutaneous anaphylaxis test was enhanced by the introduction of an (arylamino)methylene moiety into position 9 of the pyridopyrimidine ring. Compound 34, (+)-6(S)-methyl-9-[...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00376a003

    authors： Hermecz I,Horváth A,Mészáros Z,De Vos C,Rodriguez L

    更新日期：1984-10-01 00:00:00

  • Structure-activity relationships in a series of newly synthesized 1-amino-substituted ellipticine derivatives.

    abstract：:The synthesis of a series of 1-amino-substituted pyrido[4,3-b]carbazole derivatives, based on the substitution of corresponding 1-chloroellipticines, is reported. The cytotoxic properties on tumor cells grown in vitro, the in vivo acute toxicity of the most potent in vitro cytotoxic compounds, and the antitumor proper...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00185a012

    authors： Ducrocq C,Wendling F,Tourbez-Perrin M,Rivalle C,Tambourin P,Pochon F,Bisagni E,Chermann JC

    更新日期：1980-11-01 00:00:00

  • Pyrrolopyrazinedione-based inhibitors of human hormone-sensitive lipase.

    abstract：:The regulation of lipid metabolism and it's effect on glucose control and diabetes has received intense interest. Hormone-sensitive lipase (HSL) is a vital enzyme in lipid metabolism. A series of novel pyrrolopyrazinediones has been discovered that demonstrate submicromolar activity both in the enzyme assay and in a (...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm020460y

    authors： Slee DH,Bhat AS,Nguyen TN,Kish M,Lundeen K,Newman MJ,McConnell SJ

    更新日期：2003-03-27 00:00:00

  • Substituted (pyrroloamino)pyridines: potential agents for the treatment of Alzheimer's disease.

    abstract：:A novel series of substituted (pyrroloamino)pyridines was synthesized, and the compounds were evaluated for cholinomimetic-like properties in vitro (inhibition of [3H]quinuclidinyl benzilate binding) and in vivo (reversal of scopolamine-induced dementia) as potential agents for the treatment of Alzheimer's disease. Co...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm950644v

    authors： Davis L,Olsen GE,Klein JT,Kapples KJ,Huger FP,Smith CP,Petko WW,Cornfeldt M,Effland RC

    更新日期：1996-01-19 00:00:00

  • A comparative molecular field analysis model for 6-arylpyrrolo[2,1-d] [1,5]benzothiazepines binding selectively to the mitochondrial benzodiazepine receptor.

    abstract：:A series of 42 6-arylpyrrolo[2,1-d][1,5]benzothiazepines, which we have recently described as selective ligands of the mitochondrial benzodiazepine receptor (MBR) (Fiorini I.; et al. J. Med. Chem. 1994, 37, 1427-1438), have been investigated using the comparative molecular field analysis (CoMFA) approach. The resultin...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00050a007

    authors： Greco G,Novellino E,Fiorini I,Nacci V,Campiani G,Ciani SM,Garofalo A,Bernasconi P,Mennini T

    更新日期：1994-11-25 00:00:00

  • Synthesis of a tetronic acid library focused on inhibitors of tyrosine and dual-specificity protein phosphatases and its evaluation regarding VHR and cdc25B inhibition.

    abstract：:Selective inhibitors of protein tyrosine phosphatases (PTPs) and dual-specificity phosphatases (DSPs) are expected to be useful tools for clarifying the biological functions of the PTPs themselves and also to be candidates for novel therapeutics. We planned a library approach for the identification of PTP/DSP inhibito...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm0100741

    authors： Sodeoka M,Sampe R,Kojima S,Baba Y,Usui T,Ueda K,Osada H

    更新日期：2001-09-27 00:00:00

  • Synthesis, DNA cross-linking activity, and cytotoxicity of dimeric mitomycins.

    abstract：:Dimeric DNA cross-linking compounds have emerged as important new antitumor agents. We report the synthesis and biochemical evaluation of a select set of dimeric mitomycins in which the two mitomycin units are tethered at either the mitomycin C(7) amino or the aziridine N(1a) positions. Significantly, mitomycin C (1) ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm010090y

    authors： Na Y,Li VS,Nakanishi Y,Bastow KF,Kohn H

    更新日期：2001-10-11 00:00:00

  • Highly potent, orally active diester macrocyclic human renin inhibitors.

    abstract：:Replacing one amide bond in macrocyclic renin inhibitors of the general structure 1 and 2 with an ester linkage gave glutamate-derived inhibitors 3 and serine-derived inhibitors 4. While this oxygen-for-nitrogen exchange had little effect on potency in the glutamate series, potency was dramatically increased in the se...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00099a004

    authors： Weber AE,Steiner MG,Krieter PA,Colletti AE,Tata JR,Halgren TA,Ball RG,Doyle JJ,Schorn TW,Stearns RA

    更新日期：1992-10-16 00:00:00

  • Protein structure determination using a combination of comparative modeling and NMR spectroscopy. Application to the response regulator protein, Spo0F.

    abstract：:A practical combination of comparative modeling and NMR spectroscopy was used to generate a three-dimensional structure of the response regulator protein, Spo0F. The backbone structure obtained compares to the Spo0F Y13S mutant X-ray structure with an rmsd of 2.0 A. We provide results which suggest that structures obt...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm970156i

    authors： Podlogar BL,Leo GC,McDonnell PA,Loughney DA,Caldwell GW,Barrett JF

    更新日期：1997-10-10 00:00:00

  • Novel synthesis of the hexahydroimidazo[1,5b]isoquinoline scaffold: application to the synthesis of glucocorticoid receptor modulators.

    abstract：:The first stereoselective synthesis of the hexahydroimidazo[1,5b]isoquinoline (HHII) scaffold as a surrogate for the steroidal A-B ring system is described. The structure-activity relationships of the analogs derived from this scaffold show that the basic imidazole moiety is tolerated by the glucocorticoid receptor (G...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm901551w

    authors： Xiao HY,Wu DR,Malley MF,Gougoutas JZ,Habte SF,Cunningham MD,Somerville JE,Dodd JH,Barrish JC,Nadler SG,Dhar TG

    更新日期：2010-02-11 00:00:00

  • Synthesis, resolution, absolute stereochemistry, and enantioselectivity of 3',4'-dihydroxynomifensine.

    abstract：:3',4'-Dihydroxynomifensine, 8-amino-1,2,3,4-tetrahydro-4-(3,4-dihydroxyphenyl)-2-methylisoquinoli ne (1a), is an agonist of dopamine receptors in central and peripheral systems. Since this dopamine receptor agonist bears an asymmetric center at position 4, its synthesis and resolution were undertaken as part of a stud...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00367a006

    authors： Dandridge PA,Kaiser C,Brenner M,Gaitanopoulos D,Davis LD,Webb RL,Foley JJ,Sarau HM

    更新日期：1984-01-01 00:00:00

  • Structure-activity relationships for the carboxy-terminus truncated analogues of angiotension II, a new class of angiotensin II antagonists.

    abstract：:A series of analogues of the recently reported angiotensin II (AII) antagonist [Sar1]AII-(1-7)-amide or des-Phe8[Sar1]AII (3) have been prepared by solid-phase synthesis and purified by reverse-phase liquid chromatography. The agonist and antagonist properties of these carboxy-truncated analogues of AII were determine...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00167a030

    authors： Bovy PR,O'Neal JM,Olins GM,Patton DR,McMahon EG,Palomo M,Koepke JP,Salles KS,Trapani AJ,Smits GJ

    更新日期：1990-05-01 00:00:00

  • Antitumor activity and toxicity of novel nitroheterocyclic phosphoramidates.

    abstract：:A series of novel nitroheterocyclic phosphoramidates has been evaluated for antitumor activity in murine and xenograft tumor models and for toxicity in mice. Significant increases in lifespan and long-term survivors were noted in L1210 leukemia and B16 melanoma models, and both complete and partial tumor regressions w...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm000359y

    authors： Borch RF,Liu J,Joswig C,Baggs RB,Dexter DL,Mangold GL

    更新日期：2001-01-04 00:00:00

  • Synthetic HIV V3 Glycopeptide Immunogen Carrying a N334 N-Glycan Induces Glycan-Dependent Antibodies with Promiscuous Site Recognition.

    abstract：:The N332 high-mannose glycan on the HIV-1 gp120 V3-loop is the target of many bNAbs. About 17% HIV isolates carry the N332 to N334 mutation, but the antibody recognition of the N334 N-glycan and its immunogenicity are not well characterized. Here we report the chemoenzymatic synthesis, antigenicity, and immunogenicity...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.8b01290

    authors： Cai H,Zhang RS,Orwenyo J,Giddens J,Yang Q,LaBranche CC,Montefiori DC,Wang LX

    更新日期：2018-11-21 00:00:00

  • Potent fibrinolysis inhibitor discovered by shape and electrostatic complementarity to the drug tranexamic acid.

    abstract：:Protein-protein interfaces provide an important class of drug targets currently receiving increased attention. The typical design strategy to inhibit protein-protein interactions usually involves large molecules such as peptides and macrocycles. One exception is tranexamic acid (TXA), which, as a lysine mimetic, inhib...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm301818g

    authors： Boström J,Grant JA,Fjellström O,Thelin A,Gustafsson D

    更新日期：2013-04-25 00:00:00

  • Mapping the turkey erythrocyte beta receptor: a distance geometry approach.

    abstract：:Extensions and refinements of the receptor mapping method as originally developed by Crippen are presented. In a set of newly developed algorithms measures are taken to reduce the number of required energy parameters to a statistically acceptable degree. The most important measure is the incorporation of lipophilicity...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00152a017

    authors： Linschoten MR,Bultsma T,IJzerman AP,Timmerman H

    更新日期：1986-02-01 00:00:00

  • Design, synthesis, and structure--activity relationship studies for a new imidazole series of J774 macrophage specific acyl-CoA:cholesterol acyltransferase (ACAT) inhibitors.

    abstract：:Acyl-CoA:cholesterol acyltransferase (ACAT) is the primary enzyme involved in intracellular cholesterol esterification. Arterial wall infiltration by macrophages and subsequent uncontrolled esterification of cholesterol leading to foam cell formation is believed to be an important process which leads to the developmen...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00007a004

    authors： Maduskuie TP Jr,Wilde RG,Billheimer JT,Cromley DA,Germain S,Gillies PJ,Higley CA,Johnson AL,Pennev P,Shimshick EJ

    更新日期：1995-03-31 00:00:00

  • Pharmacophore based receptor modeling: the case of adenosine A3 receptor antagonists. An approach to the optimization of protein models.

    abstract：:To design and synthesize new potent and selective antagonists of the human A(3) adenosine receptor, pharmacophoric hypotheses were generated with the software Catalyst for a comprehensive set of compounds retrieved from previous literature. Three of these pharmacophores were used to drive the optimization of a molecul...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm051112+

    authors： Tafi A,Bernardini C,Botta M,Corelli F,Andreini M,Martinelli A,Ortore G,Baraldi PG,Fruttarolo F,Borea PA,Tuccinardi T

    更新日期：2006-07-13 00:00:00

  • Immuno-suppressive effect of blocking the CD28 signaling pathway in T-cells by an active component of Echinacea found by a novel pharmaceutical screening method.

    abstract：:AFTIR (after flowing through immobilized receptor) is a novel method for screening herbal extracts for pharmaceutical properties. Using AFTIR, we identified Cynarin in Echinacea purpurea by its selective binding to chip immobilized CD28, a receptor of T-cells, which is instrumental to immune functioning. The results o...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm0509039

    authors： Dong GC,Chuang PH,Forrest MD,Lin YC,Chen HM

    更新日期：2006-03-23 00:00:00

  • Synthesis and anticonvulsant properties of 2,3,3a,4-tetrahydro-1H-pyrrolo[1,2-a]benzimidazol-1-ones.

    abstract：:A series of 2,3,3a,4-tetrahydro-1H-pyrrolo[1,2-a]benzimidazol-1-ones were synthesized and evaluated for anticonvulsant activity in DBA/2 mice against sound-induced seizures and in rats against maximal electroshock-induced seizures. Most of the derivatives showed an anticonvulsant effect better than that of valproate, ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00121a019

    authors： Chimirri A,De Sarro A,De Sarro G,Grasso S,Trimarchi GR,Zappalà M

    更新日期：1989-01-01 00:00:00