当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Identification and characterization of small molecule inhibitors of a class I histone deacetylase from Plasmodium falciparum.

Identification and characterization of small molecule inhibitors of a class I histone deacetylase from Plasmodium falciparum.

Abstract：

:A library of approximately 2000 small molecules biased toward inhibition of histone deacetylases was assayed for antimalarial activity in a high-throughput P. falciparum viability assay. Active compounds were cross-analyzed for induction of histone hyperacetylation in a human myeloma cell line to identify HDAC inhibitors with selectivity for P. falciparum over the human host. To verify on-target selectivity, pfHDAC-1 was expressed and purified and a biochemical assay for pfHDAC-1 activity was established.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Patel V,Mazitschek R,Coleman B,Nguyen C,Urgaonkar S,Cortese J,Barker RH,Greenberg E,Tang W,Bradner JE,Schreiber SL,Duraisingh MT,Wirth DF,Clardy J

doi

10.1021/jm801654y

subject

Has Abstract

pub_date

2009-04-23 00:00:00

pages

2185-7

issue

8

eissn

0022-2623

issn

1520-4804

journal_volume

52

pub_type

杂志文章

相关文献

JOURNAL OF MEDICINAL CHEMISTRY文献大全
  • MutT Homolog 1 (MTH1): The Silencing of a Target.

    abstract：:MTH1 is a member of the nudix phosphohydrolase superfamily of enzymes, and it is involved in nucleotide pool homeostasis. The protein exerts its scavenging action by hydrolyzing oxidized nucleotides, thus avoiding their misincorporation into replicating DNA. Recent reports have validated its inhibition as a potential ...

    journal_title：Journal of medicinal chemistry

    pub_type： 评论,杂志文章

    doi：10.1021/acs.jmedchem.6b00283

    authors： Papeo G

    更新日期：2016-03-24 00:00:00

  • (-)-Arctigenin as a lead structure for inhibitors of human immunodeficiency virus type-1 integrase.

    abstract：:The natural dibenzylbutyrolactone type lignanolide (-)-arctigenin (2), an inhibitor of human immunodeficiency virus type-1 (HIV-1) replication in infected human cell systems, was found to suppress the integration of proviral DNA into the cellular DNA genome. In the present study 2 was tested with purified HIV-1 integr...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm950387u

    authors： Eich E,Pertz H,Kaloga M,Schulz J,Fesen MR,Mazumder A,Pommier Y

    更新日期：1996-01-05 00:00:00

  • Discovery of Hydrolysis-Resistant Isoindoline N-Acyl Amino Acid Analogues that Stimulate Mitochondrial Respiration.

    abstract：:N-Acyl amino acids directly bind mitochondria and function as endogenous uncouplers of UCP1-independent respiration. We found that administration of N-acyl amino acids to mice improves glucose homeostasis and increases energy expenditure, indicating that this pathway might be useful for treating obesity and associated...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.8b00029

    authors： Lin H,Long JZ,Roche AM,Svensson KJ,Dou FY,Chang MR,Strutzenberg T,Ruiz C,Cameron MD,Novick SJ,Berdan CA,Louie SM,Nomura DK,Spiegelman BM,Griffin PR,Kamenecka TM

    更新日期：2018-04-12 00:00:00

  • Further studies on arylpiperazinyl alkyl pyridazinones: discovery of an exceptionally potent, orally active, antinociceptive agent in thermally induced pain.

    abstract：:A number of pyridazinone derivatives bearing an arylpiperazinylalkyl chain were synthesized and tested icv in a model of acute nociception induced by thermal stimuli in mice (tail flick). The most interesting and potent compound in this series was 6a, which showed an ED(50) = 3.5 microg, a value about 3-fold higher wi...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm900458r

    authors： Biancalani C,Giovannoni MP,Pieretti S,Cesari N,Graziano A,Vergelli C,Cilibrizzi A,Di Gianuario A,Colucci M,Mangano G,Garrone B,Polenzani L,Dal Piaz V

    更新日期：2009-12-10 00:00:00

  • The development of cyclic sulfolanes as novel and high-affinity P2 ligands for HIV-1 protease inhibitors.

    abstract：:Design and synthesis of a novel series of protease inhibitors incorporating conformationally constrained cyclic ligands for the S2-substrate binding site of HIV-1 protease is described. We recently reported urethanes of 3-tetrahydrofuranyl as P2 ligands for HIV-1 protease inhibitors. Subsequently, we have found that t...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00034a016

    authors： Ghosh AK,Lee HY,Thompson WJ,Culberson C,Holloway MK,McKee SP,Munson PM,Duong TT,Smith AM,Darke PL

    更新日期：1994-04-15 00:00:00

  • Discovery of danoprevir (ITMN-191/R7227), a highly selective and potent inhibitor of hepatitis C virus (HCV) NS3/4A protease.

    abstract：:HCV serine protease NS3 represents an attractive drug target because it is not only essential for viral replication but also implicated in the viral evasion of the host immune response pathway through direct cleavage of key proteins in the human innate immune system. Through structure-based drug design and optimizatio...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm400164c

    authors： Jiang Y,Andrews SW,Condroski KR,Buckman B,Serebryany V,Wenglowsky S,Kennedy AL,Madduru MR,Wang B,Lyon M,Doherty GA,Woodard BT,Lemieux C,Geck Do M,Zhang H,Ballard J,Vigers G,Brandhuber BJ,Stengel P,Josey JA,Beigelm

    更新日期：2014-03-13 00:00:00

  • N- and 2-substituted N-(phenylsulfonyl)glycines as inhibitors of rat lens aldose reductase.

    abstract：:A variety of N-(phenylsulfonyl)-N-phenylglycines 5, N-(phenylsulfonyl)-2-phenylglycines 6, and N-(phenylsulfonyl)anthranilic acids 7 were prepared as analogues of the N-(phenylsulfonyl)glycine 1 aldose reductase inhibitors. In the rat lens assay, several derivatives of 5 display greater inhibitory activity than the co...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00121a027

    authors： DeRuiter J,Borne RF,Mayfield CA

    更新日期：1989-01-01 00:00:00

  • Structure-Activity Relationship, Drug Metabolism and Pharmacokinetics Properties Optimization, and in Vivo Studies of New Brain Penetrant Triple T-Type Calcium Channel Blockers.

    abstract：:Despite the availability of numerous antiepileptic drugs, 20-30% of epileptic patients are pharmacoresistant with seizures not appropriately controlled. Consequently, new strategies to address this unmet medical need are required. T-type calcium channels play a key role in neuronal excitability and burst firing, and s...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.6b01356

    authors： Siegrist R,Pozzi D,Jacob G,Torrisi C,Colas K,Braibant B,Mawet J,Pfeifer T,de Kanter R,Roch C,Kessler M,Moon R,Corminboeuf O,Bezençon O

    更新日期：2016-12-08 00:00:00

  • Structure-activity relationships in the trans-hexahydroindolo[4,3-ab]phenanthridine ("benzergoline") series. 2. Resolution, absolute configuration, and dopaminergic activity of the selective D1 agonist CY 208-243 and its implication for an "extended rotam

    abstract：:4,6,6a,7,8,12b-Hexahydroindolo[4,3-ab]phenanthridines ("benzergolines") was the first structural class of potent and selective dopamine D1 agonists lacking a catechol group. In order to determine the enantioselectivity of the 7-methyl derivative in the adenylate cyclase assay, its 5,5a-dihydro precursor was resolved a...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00060a004

    authors： Seiler MP,Floersheim P,Markstein R,Widmer A

    更新日期：1993-04-16 00:00:00

  • Shooting for selective druglike G-quadruplex binders: evidence for telomeric DNA damage and tumor cell death.

    abstract：:Targeting of DNA secondary structures, such as G-quadruplexes, is now considered an appealing opportunity for drug intervention in anticancer therapy. So far, efforts made in the discovery of chemotypes able to target G-quadruplexes mainly succeeded in the identification of a number of polyaromatic compounds featuring...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm301019w

    authors： Cosconati S,Rizzo A,Trotta R,Pagano B,Iachettini S,De Tito S,Lauri I,Fotticchia I,Giustiniano M,Marinelli L,Giancola C,Novellino E,Biroccio A,Randazzo A

    更新日期：2012-11-26 00:00:00

  • 1,4-Oxazine β-Secretase 1 (BACE1) Inhibitors: From Hit Generation to Orally Bioavailable Brain Penetrant Leads.

    abstract：:1,4-Oxazines are presented, which show good in vitro inhibition in enzymatic and cellular BACE1 assays. We describe lead optimization focused on reducing the amidine pKa while optimizing interactions in the BACE1 active site. Our strategy permitted modulation of properties such as permeation and especially P-glycoprot...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.5b01101

    authors： Rombouts FJ,Tresadern G,Delgado O,Martínez-Lamenca C,Van Gool M,García-Molina A,Alonso de Diego SA,Oehlrich D,Prokopcova H,Alonso JM,Austin N,Borghys H,Van Brandt S,Surkyn M,De Cleyn M,Vos A,Alexander R,Macdonald G,Mo

    更新日期：2015-10-22 00:00:00

  • Discovery of N-((3R,4R)-4-Fluoro-1-(6-((3-methoxy-1-methyl-1H-pyrazol-4-yl)amino)-9-methyl-9H-purin-2-yl)pyrrolidine-3-yl)acrylamide (PF-06747775) through Structure-Based Drug Design: A High Affinity Irreversible Inhibitor Targeting Oncogenic EGFR Mutants

    abstract：:Mutant epidermal growth factor receptor (EGFR) is a major driver of non-small-cell lung cancer (NSCLC). Marketed first generation inhibitors, such as erlotinib, effect a transient beneficial response in EGFR mutant NSCLC patients before resistance mechanisms render these inhibitors ineffective. Secondary oncogenic EGF...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.6b01894

    authors： Planken S,Behenna DC,Nair SK,Johnson TO,Nagata A,Almaden C,Bailey S,Ballard TE,Bernier L,Cheng H,Cho-Schultz S,Dalvie D,Deal JG,Dinh DM,Edwards MP,Ferre RA,Gajiwala KS,Hemkens M,Kania RS,Kath JC,Matthews J,Murra

    更新日期：2017-04-13 00:00:00

  • Synthesis and antiviral activity of 4-benzyl pyridinone derivatives as potent and selective non-nucleoside human immunodeficiency virus type 1 reverse transcriptase inhibitors.

    abstract：:Several 4-benzyl analogues of 5-ethyl-6-methyl-4-(phenylthio)pyridin-2(1H)-ones were synthesized and evaluated for their anti-HIV-l activities. Key transformations include metalation at the 4-C-position of 5-ethyl-2-methoxy-6-methyl-3-pivaloylaminopyridine (5) and its coupling with benzyl bromide or benzaldehyde deriv...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm0009437

    authors： Dollé V,Nguyen CH,Legraverend M,Aubertin AM,Kirn A,Andreola ML,Ventura M,Tarrago-Litvak L,Bisagni E

    更新日期：2000-10-19 00:00:00

  • Reducing the peptidyl features of caspase-3 inhibitors: a structural analysis.

    abstract：:Caspases are cysteine proteases that specifically cleave Asp-Xxx bonds. They are key agents in inflammation and apoptosis and are attractive targets for therapy against inflammation, neurodegeneration, ischemia, and cancer. Many caspase structures are known, but most involve either peptide or protein inhibitors, unatt...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm0305523

    authors： Becker JW,Rotonda J,Soisson SM,Aspiotis R,Bayly C,Francoeur S,Gallant M,Garcia-Calvo M,Giroux A,Grimm E,Han Y,McKay D,Nicholson DW,Peterson E,Renaud J,Roy S,Thornberry N,Zamboni R

    更新日期：2004-05-06 00:00:00

  • Function of the D-alanine:D-alanine ligase lid loop: a molecular modeling and bioactivity study.

    abstract：:D-Alanine:D-alanine ligase (Ddl) is an essential ATP-dependent bacterial enzyme involved in peptidoglycan biosynthesis. Discovery of Ddl inhibitors not competitive with ATP has proven to be difficult because the Ddl bimolecular d-alanine binding pocket is very restricted, as is accessibility to the active site for lar...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm3006965

    authors： Hrast M,Vehar B,Turk S,Konc J,Gobec S,Janežič D

    更新日期：2012-08-09 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

  • Computer-assisted structure-activity studies of chemical carcinogens. Aromatic amines.

    abstract：:Studies of molecular structure-carcinogenicity relations for a set of 157 aromatic amines are reported. A computer-assisted approach using pattern-recognition methods was used to develop a series of discriminants for aromatic amino carcinogenic potential. The 157 compounds were divided into subsets according to tumor ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00135a003

    authors： Yuta K,Jurs PC

    更新日期：1981-03-01 00:00:00

  • Design of rat renin inhibitory peptides.

    abstract：:Because several well-studied strains of rats manifest spontaneous hypertension, we set out to design a renin inhibitor suitable for use in this species. On the basis of the sequence of the renin substrate, a series of substrate analogue inhibitory peptides were synthesized by systematically modifying the P5, P3, P2, P...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00117a003

    authors： Hui KY,Holtzman EJ,Quinones MA,Hollenberg NK,Haber E

    更新日期：1988-09-01 00:00:00

  • 1-Aryl-3,5-dihydro-4H-2,3-benzodiazepin-4-ones: novel AMPA receptor antagonists.

    abstract：:Our previous publication (Eur. J. Pharmacol. 1995, 294, 411-422) reported preliminary chemical and biological studies of some 2,3-benzodiazepines, analogues of 1-(4-aminophenyl)-4-methyl-7,8-(methylenedioxy)-5H-2,3-benzodiazepine (1, GYKI 52466), which have been shown to possess significant anticonvulsant activity. Th...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm960506l

    authors： Chimirri A,De Sarro G,De Sarro A,Gitto R,Grasso S,Quartarone S,Zappalà M,Giusti P,Libri V,Constanti A,Chapman AG

    更新日期：1997-04-11 00:00:00

  • Synthesis and antibacterial properties of methylsulfinyl and methylsulfonyl analongs of some nitrofurans.

    abstract：:The sulfoxides 5-methylsulfinyl-2-furaldehyde semicarbazone (2) and 1-[(5-methylsulfinyl-2-fufurylidene)amino]hydantoin (3) as well as the sulfones 1-[(5-methylsulfonyl-2-furfurylidene)animo]hydantoin (1) and 1-(5-methylsulfonly-2-furyl)-2-(6-amino-3-p-ridazyl)ethylene hydrochloride (4) have been prepared and tested f...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00245a030

    authors： Ekström B,Ovesson M,Pring BG

    更新日期：1975-11-01 00:00:00

  • Targeting the MKK7-JNK (Mitogen-Activated Protein Kinase Kinase 7-c-Jun N-Terminal Kinase) Pathway with Covalent Inhibitors.

    abstract：:The protein kinase MKK7 is linked to neuronal development and the onset of cancer. The field, however, lacks high-quality functional probes that would allow for the dissection of its detailed functions. Against this background, we describe an effective covalent inhibitor of MKK7 based on the pyrazolopyrimidine scaffol...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.9b00102

    authors： Wolle P,Hardick J,Cronin SJF,Engel J,Baumann M,Lategahn J,Penninger JM,Rauh D

    更新日期：2019-03-14 00:00:00

  • Improved delivery through biological membranes. 1. Synthesis and properties of 1-methyl-1,6-dihydropyridine-2-carbaldoxime, a pro-drug of N-methylpyridinium-2-carbaldoxime chloride.

    abstract：:A dihydropyridine-pyridine type redox pro-drug system was developed for delivering quaternary pyridinium salts through biological membranes. As a first application, the dihydropyridine derivative of N-methylpyridinium-2-carbaldoxime chloride (2-PAM) was synthesized using a reduction-addition-elimination sequence. The ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00223a017

    authors： Bodor N,Shek E,Higuchi T

    更新日期：1976-01-01 00:00:00

  • Optimization of Potent ATAD2 and CECR2 Bromodomain Inhibitors with an Atypical Binding Mode.

    abstract：:Most bromodomain inhibitors mimic the interactions of the natural acetylated lysine (KAc) histone substrate through key interactions with conserved asparagine and tyrosine residues within the binding pocket. Herein we report the optimization of a series of phenyl sulfonamides that exhibit a novel mode of binding to no...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.0c00021

    authors： Lucas SCC,Atkinson SJ,Bamborough P,Barnett H,Chung CW,Gordon L,Mitchell DJ,Phillipou A,Prinjha RK,Sheppard RJ,Tomkinson NCO,Watson RJ,Demont EH

    更新日期：2020-05-28 00:00:00

  • Bispyridinium dienes: histone deacetylase inhibitors with selective activities.

    abstract：:A novel synthetic route to the cyclostellettamines 1 using as the key step a microwave-mediated macrocyclic ring-closing metathesis of precursors bispyridinium dienes 10 followed by catalytic hydrogenation has been developed. The open-chain bispyridinium dienes 10 showed uniformly higher histone deacetylase (HDAC) inh...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm070028m

    authors： Pérez-Balado C,Nebbioso A,Rodríguez-Graña P,Minichiello A,Miceli M,Altucci L,de Lera AR

    更新日期：2007-05-17 00:00:00

  • Bisphosphonate inhibition of phosphoglycerate kinase: quantitative structure-activity relationship and pharmacophore modeling investigation.

    abstract：:We report the results of a three-dimensional quantitative structure-activity relationship (3D-QSAR) and pharmacophore modeling investigation of the interaction of the enzyme 3-phosphoglycerate kinase (PGK) with aryl and alkyl bisphosphonates. For the human enzyme, the IC50 values are predicted within a factor of 2 ove...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm0604833

    authors： Kotsikorou E,Sahota G,Oldfield E

    更新日期：2006-11-16 00:00:00

  • Detailed analysis of scoring functions for virtual screening.

    abstract：:We present a comprehensive study of the performance of fast scoring functions for library docking using the program FlexX as the docking engine. Four scoring functions, among them two recently developed knowledge-based potentials, are evaluated on seven target proteins whose binding sites represent a wide range of siz...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm0003992

    authors： Stahl M,Rarey M

    更新日期：2001-03-29 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

  • Design, synthesis, and biological activity of m-tyrosine-based 16- and 17-membered macrocyclic inhibitors of hepatitis C virus NS3 serine protease.

    abstract：:The limited efficacy and considerable side effects of currently available therapies for the treatment of hepatitis C virus (HCV) infection have prompted significant efforts toward the development of safe and effective new therapeutics. The pentapeptide alpha-ketoamides of type 1 were weak HCV inhibitors with a binding...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm050323b

    authors： Chen KX,Njoroge FG,Pichardo J,Prongay A,Butkiewicz N,Yao N,Madison V,Girijavallabhan V

    更新日期：2005-10-06 00:00:00

  • Trypanocidal activity of conformationally restricted pentamidine congeners.

    abstract：:A series of conformationally restricted congeners of pentamidine in which the flexible pentyl bridge of pentamidine was replaced by trans-1,2-bismethylenecyclopropyl, phenyl, pyridinyl, piperazinyl, homopiperazinyl, and piperidinyl groups were synthesized. The compounds were evaluated for trypanocidal activity in vitr...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm020375q

    authors： Donkor IO,Huang TL,Tao B,Rattendi D,Lane S,Vargas M,Goldberg B,Bacchi C

    更新日期：2003-03-13 00:00:00