Abstract:
:In this article we introduce a molecular docking algorithm called MolDock. MolDock is based on a new heuristic search algorithm that combines differential evolution with a cavity prediction algorithm. The docking scoring function of MolDock is an extension of the piecewise linear potential (PLP) including new hydrogen bonding and electrostatic terms. To further improve docking accuracy, a re-ranking scoring function is introduced, which identifies the most promising docking solution from the solutions obtained by the docking algorithm. The docking accuracy of MolDock has been evaluated by docking flexible ligands to 77 protein targets. MolDock was able to identify the correct binding mode of 87% of the complexes. In comparison, the accuracy of Glide and Surflex is 82% and 75%, respectively. FlexX obtained 58% and GOLD 78% on subsets containing 76 and 55 cases, respectively.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Thomsen R,Christensen MHdoi
10.1021/jm051197esubject
Has Abstractpub_date
2006-06-01 00:00:00pages
3315-21issue
11eissn
0022-2623issn
1520-4804journal_volume
49pub_type
杂志文章abstract::Farnesoid X receptor (FXR) agonists are emerging as important potential therapeutics for the treatment of nonalcoholic steatohepatitis (NASH) patients, as they exert positive effects on multiple aspects of the disease. FXR agonists reduce lipid accumulation in the liver, hepatocellular inflammation, hepatic injury, an...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.9b01621
更新日期:2020-04-23 00:00:00
abstract::Fragment-based drug design exploits initial screening of low molecular weight compounds and their concomitant affinity improvement. The multitude of possible chemical modifications highlights the necessity to obtain structural information about the binding mode of a fragment. Herein we describe a novel NMR methodology...
journal_title:Journal of medicinal chemistry
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abstract::Stereoisomers of fenoterol and six fenoterol derivatives have been synthesized and their binding affinities for the beta2 adrenergic receptor (Kibeta2-AR), the subtype selectivity relative to the beta1-AR (Kibeta1-AR/Kibeta2-AR) and their functional activities were determined. Of the 26 compounds synthesized in the st...
journal_title:Journal of medicinal chemistry
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更新日期:2007-06-14 00:00:00
abstract::A significant improvement in agonist activity of the previously described 2-aryloctahydrophenanthrene-2,3,7-triol series of dissociated glucocorticoid receptor agonists (DAGRs) was achieved by modifying the substitution at C3 from (S)-3-hydroxy to (R)-3-hydroxy-3-methyl. The IC50 of the prototype 13 in the efficacy as...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
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更新日期:2015-03-26 00:00:00
abstract::A series of substituted 4,6-dihydrospiro[[1,2,3]triazolo[4,5-b]pyridine-7,3'-indoline]-2',5(3H)-dione analogues were synthesized and evaluated as potent dengue virus inhibitors. Throughout a structure-activity relationship exploration on the amide of the indolone moiety, a wide range of substitutions were found to be ...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.9b00698
更新日期:2019-09-12 00:00:00
abstract::Acid ceramidase (AC) is an intracellular cysteine amidase that catalyzes the hydrolysis of the lipid messenger ceramide. By regulating ceramide levels in cells, AC may contribute to the regulation of cancer cell proliferation and senescence and to the response to cancer therapy. We recently identified the antitumoral ...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm301879g
更新日期:2013-05-09 00:00:00
abstract::The important enzyme 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) is known to regulate intracellular levels of biologically active steroids, namely, androgens and estrogens. In an effort to develop potent inhibitors of 17 beta-HSD for reducing the levels of active steroids, we found that steroidal spiro-gamma-la...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00022a018
更新日期:1995-10-27 00:00:00
abstract::A series of different synthetic approaches to novel GABA uptake inhibitors are described, leading to examples which are derivatives of nipecotic acid and guvacine, substituted at nitrogen by 4,4-diaryl-3-butenyl or 2-(diphenylmethoxy)ethyl moieties. The in vitro value for inhibition of [3H]-GABA uptake in rat synaptos...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00064a005
更新日期:1993-06-11 00:00:00
abstract::The sea anemone peptide APETx2 is a potent and selective blocker of acid-sensing ion channel 3 (ASIC3). APETx2 is analgesic in a variety of rodent pain models, but the lack of knowledge of its pharmacophore and binding site on ASIC3 has impeded development of improved analogues. Here we present a detailed structure-ac...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm501400p
更新日期:2014-11-13 00:00:00
abstract::By use of the effectively cleaved beta-secretase (BACE) substrate (1), incorporation of a statine in P(1) resulted in a weak inhibitor 13 of the enzyme. Further substitution of P(1)'-Asp by P(1)'-Val in 13 results in a potent inhibitor 22 of BACE. Removal of the P(10)-P(5) residues on the N-terminal part of inhibitor ...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm0155695
更新日期:2002-01-17 00:00:00
abstract::The IAPs are key regulators of the apoptotic pathways and are commonly overexpressed in many cancer cells. IAPs contain one to three BIR domains that are crucial for their inhibitory function. The pro-survival properties of XIAP come from binding of the BIR domains to the pro-apoptotic caspases. The BIR3 domain of XIA...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm400732v
更新日期:2013-10-24 00:00:00
abstract::N-Myristoyltransferase (NMT) is an attractive antiprotozoan drug target. A lead-hopping approach was utilized in the design and synthesis of novel benzo[b]thiophene-containing inhibitors of Plasmodium falciparum (Pf) and Plasmodium vivax (Pv) NMT. These inhibitors are selective against Homo sapiens NMT1 (HsNMT), have ...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm301474t
更新日期:2013-01-10 00:00:00
abstract::Four nucleoside analogues ( 1- 4) containing a common heterocyclic base, 4(7)-amino-6(5) H-imidazo[4,5- d]pyridazin-7(4)one, were screened against calf-intestine adenosine deaminase. Compounds 1 and 3 with K(i) values of 10-12 microM are more than four times as potent inhibitors of ADA compared with 2 and 4, with K(i)...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm700931t
更新日期:2008-02-14 00:00:00
abstract::1-beta-D-Arabinofuranosylthymine (aThy; ara-T) is a potent selective anti herpes simplex virus drug. Its anhydro analogue, 2,2'-anhydro-aThy, was shown to be 9-fold less active and at least 3-fold less toxic than aThy. This compound was relatively stable at physiological pH and in strong acid but was rapidly hydrolyze...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00354a025
更新日期:1982-12-01 00:00:00
abstract::We recently described a number of inhibitors of P450(17 alpha), the key enzyme of androgen biosynthesis. Here, we report the synthesis and activity of novel 17-imidazolyl, pyrazolyl, and isoxazolyl androstene derivatives as potential agents for the treatment of prostatic cancer. A number of 17-(4'-Imidazolyl) derivati...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm970337k
更新日期:1997-09-26 00:00:00
abstract::TYK2 is an emerging drug target for various human autoimmune diseases. However, discovery of selective TYK2 inhibitor over other JAK family members (i.e., JAK1, 2, 3) by targeting the catalytically active site (Janus Homologue 1 (JH1) domain) is challenging. This Viewpoint discusses the discovery of a series of N-meth...
journal_title:Journal of medicinal chemistry
pub_type: 评论,杂志文章
doi:10.1021/acs.jmedchem.9b01612
更新日期:2019-10-24 00:00:00
abstract::Polycomb Repressive Complex 2 (PRC2) modulates the chromatin structure and transcriptional repression by trimethylation lysine 27 of histone H3 (H3K27me3), a process that necessitates the protein-protein interaction (PPI) between the catalytic subunit EZH2 and EED. Deregulated PRC2 is intimately involved in tumorigene...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm501230c
更新日期:2014-11-26 00:00:00
abstract::An improved method for the synthesis of cardiac glycosides was used to prepare 3 beta-glucosides of digitoxigenin derivatives in which the 17 beta side chain was CH=CHX (X = COOH, CONH2, COCH3, CN, or COOR). We compared the inotropic activity of the compounds with that of digitoxigenin glucoside using guinea pig left ...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00352a025
更新日期:1982-10-01 00:00:00
abstract::We have prepared azabicyclo[3.2.1] derivatives (C-3-substituted tropanes) that bind with high affinity to the dopamine transporter and inhibit dopamine reuptake. Within the series, 3-[2-[bis-(4-fluorophenyl)methoxy]ethylidene]-8-methyl-8-azabicyclo[3.2.1]octane (8) was found to have the highest affinity and selectivit...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm0101592
更新日期:2001-11-08 00:00:00
abstract::Understanding the "limits and boundaries" of the central nervous system (CNS) property space is a critical aspect of modern CNS drug design. Medicinal chemists are often guided by the physicochemical properties of marketed CNS drugs, which are heavily biased toward "traditional" aminergic targets and commonly describe...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章,收录出版
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更新日期:2017-07-27 00:00:00
abstract::Mono- and diphenylpyridazine ureido derivatives, structurally related to DuP 128, were synthesized and tested for their inhibitory activity against ACAT isolated from rat liver microsomes. Several compounds displayed ACAT inhibition in the micromolar range. The amino derivatives 4a-c were also tested against hACAT-1 a...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm050703x
更新日期:2005-12-01 00:00:00
abstract::S1P5 is one of 5 receptors for sphingosine-1-phosphate and is highly expressed on endothelial cells within the blood-brain barrier, where it maintains barrier integrity in in vitro models (J. Neuroinflamm. 2012, 9, 133). Little more is known about the effects of S1P5 modulation due to the absence of tool molecules wit...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.5b00928
更新日期:2015-12-10 00:00:00
abstract::A series of both aliphatic and aromatic amides and aromatic amidines derived from 2-amino-1,10-phenanthroline (3) according to the Topliss scheme were synthesized and subsequently tested for antimycoplasmal potency. Although the compounds themselves showed no activity, in the presence of a nontoxic copper concentratio...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00107a045
更新日期:1991-03-01 00:00:00
abstract::Investigation of tricyclic heterocycles related to the 2-arylpyrazolo[4,3-c]quinolin-3(5H)-ones, structures with high affinity for the benzodiazepine (BZ) receptor, led to the synthesis of 2-phenyl-[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one, a compound with 4 nM binding affinity to the BZ receptor. Analogues were prep...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00105a044
更新日期:1991-01-01 00:00:00
abstract::A series of pyridine-2-carboxaldehyde N-oxide and pyridine-2-carboxaldehyde (thio)phosphoric hydrazones and two cupric chelates was synthesized. The hydrazones, chelates, and combinations of hydrazones and cupric chloride were tested against mice bearing P388 lymphocytic leukemia, Sarcoma 180, or Ehrlich carcinoma asc...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00209a011
更新日期:1978-11-01 00:00:00
abstract::[(Pyridylmethyl)sulfinyl]benzimidazoles 1 (PSBs) are a class of highly potent antisecretory (H+,K+)-ATPase inhibitors which need to be activated by acid to form their active principle, the cyclic sulfenamide 4. Selective inhibitors of the (H+,K+)-ATPase in vivo give rise to the nonselective thiophile 4 solely at low p...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00084a010
更新日期:1992-03-20 00:00:00
abstract::The ability of a series of substituted kynurenic acids, thienopyridinonecarboxylic acids, and related compounds to inhibit the binding of nerve growth factor (NGF) to the p75 NGF receptor (NGFR) was evaluated in a radioligand binding assay that utilized a biotinylated derivative of the extracellular domain of p75 NGFR...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00022a008
更新日期:1995-10-27 00:00:00
abstract::Alkenylidene bisphenols are prepared by condensation of an appropriate phenol with a haloacetaldehyde, followed by base-induced elimination, or by condensation of the corresponding aryl methyl ether, elimination, and deprotection of the phenol with boron tribromide. The resulting compounds may be further elaborated by...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00194a022
更新日期:1979-08-01 00:00:00
abstract::The discovery of isozyme-selective histone deacetylase (HDAC) inhibitors is critical for understanding the biological functions of individual HDACs and for validating HDACs as drug targets. The isozyme HDAC10 contributes to chemotherapy resistance and has recently been described to be a polyamine deacetylase, but no s...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.8b01936
更新日期:2019-05-09 00:00:00
abstract::To find Delta(8)-Delta(7) sterol isomerase (EBP) selective ligands, various arylpiperazines previously studied and structurally related to some sigma receptors ligands were preliminarily screened. Consequently, a novel series of 2- or 2,6-disubstituted (CH(3), CH(3)O, Cl, F) cis- and trans-4-(4-aryl)cyclohexyl-1-(2-py...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm800965b
更新日期:2008-12-11 00:00:00