Gabor Imre

ChemAxon, Budapeŝto, Budapest, Hungary

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Publications (10)23.55 Total impact

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    ABSTRACT: 3D shape- or volume-based virtual screening is a broadly used approach in drug discovery. In recent years a large number of publications have appeared in which these tools were compared to not only competitive methods but to docking studies as well. Studies often showed that the effectiveness of docking could be highly variable due to a large number of possible confounding factors, while ligand-based, shape-based approaches were more consistent. Here, we describe a novel, fully flexible shape-based virtual screening algorithm that does not require previous 3D conformation or conformer generation. Due to its solid consistency it can easily be used on desktop computers by non-expert scientists. The algorithm is demonstrated in a study for the investigation of ß-secretase inhibitors.
    Journal of Chemical Information and Modeling 02/2014; · 4.30 Impact Factor
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    A Kalaszi, G Imre, M Vargyas
    Journal of Cheminformatics 01/2011; 3:1-1. · 3.59 Impact Factor
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    ABSTRACT: The linear relationship is still the most important tool for establishing connection between correlating features, properties. The name “parameter-free linear relationship” (PFLR) stands for a new formalism, a generalized interpolation scheme, which can be readily used for predicting biological activities or other properties in 3D QSAR manner. Our studies demonstrate the good predictive power of PFLR even when used with a simple set of 3D molecular descriptors without constructing a grid representation of the features. PFLR allows completing most of the computations solely in the space of descriptors, without experimental training data, which, however, bears no importance in the case of 3D QSAR but might be advantageous in other areas where multidimensional linear regression or partial least squares based methods are applicable.
    Journal of Mathematical Chemistry 02/2009; 45(3):598-606. · 1.23 Impact Factor
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    Gabor Imre
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    ABSTRACT: Activation of group II metabotropic glutamate (mGlu2/3) receptors reduces excessive glutamate release that is often associated with neurodegenerative and psychiatric disorders. This finding encouraged the search for potent and selective agonists as potential therapeutic agents. The search led to the discovery of LY379268 {(-)-2-oxa-4-aminobicyclo[3.1.0]hexane-4,6-dicarboxylic acid}, which is a highly potent and systemically available mGlu2/3 receptor agonist. LY379268 was effective in several animal models of stroke, epilepsy, drug abuse, schizophrenia, and pain. Suppression of motor activity is the major side effect of LY379268. Upon repeated administration tolerance develops to this side effect, while the therapeutic effects of LY379268 remain. To date, no clinical data with LY379268 are available. This review article summarizes the preclinical pharmacology of LY379268.
    CNS Drug Reviews 02/2007; 13(4):444-64. · 4.92 Impact Factor
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    ABSTRACT: Most of the drug molecules exhibit their biological activity through binding to the target protein. When the D structure of the binding site is unknown, pure ligand-based approaches are often used to perceive the 3D pharmacophore. However, dealing with conformational flexibility of ligands in such methods is still in the frontline of the current research. The special thermodynamic properties of the binding of flexible molecules, as derived here, show that the probability of the bioactive conformations in solution can determine the likelihood of binding. The binding activities can be obtained experimentally, while the probability of conformations in solution can be computed. Our present paper discusses the thermodynamic basis of performing 3D QSAR studies on molecules, with considerable conformational flexibility. In addition, we supply an algorithm to locate the bioactive conformations. The work is initiated to find the binding conformation of the therapeutically promising mucin epitope pentapeptides.
    Journal of Molecular Structure-theochem - J MOL STRUC-THEOCHEM. 01/2007; 823(1):16-27.
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    ABSTRACT: Acute treatment with LY354740 {1S,2S,5R,6S-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylate monohydrate}, a potent and selective agonist for group II metabotropic glutamate receptors (mGlu2/3), has previously been shown to block some schizophrenia-like effects of N-methyl-D-aspartate (NMDA) receptor antagonists, suggesting a novel therapeutic strategy for schizophrenia. The present study examined the effects of subchronic pretreatment with LY354740 (0.3, 3 and 10 mg/kg i.p.) on ketamine-evoked (12 mg/kg s.c.) prepulse inhibition deficits, hyperlocomotion and c-fos expression. At all doses, LY354740 failed to reverse both behavioral and neuronal effects of the ketamine. These results therefore do not support the putative antipsychotic role of LY354740.
    European Journal of Pharmacology 09/2006; 544(1-3):77-81. · 2.59 Impact Factor
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    ABSTRACT: One of the functions of group II metabotropic glutamate receptors (mGluR2/3) is to modulate glutamate release. Thus, targeting mGluR2/3s might be a novel treatment for several psychiatric disorders associated with inappropriate glutamatergic neurotransmission, such as schizophrenia. In an effort to evaluate the antipsychotic properties of LY379268, a potent and selective mGluR2/3 agonist, we examined its effect on ketamine-evoked hyperlocomotion and sensorimotor gating deficit (PPI) in rats, an animal model of schizophrenia. We also measured the ex vivo tissue level of glutamate (Glu), dopamine (DA) and serotonin (5-HT) as well as the DA metabolites DOPAC and the major 5-HT metabolite HIAA to determine the neurochemical effects of ketamine (12 mg/kg) and LY379268 (1 mg/kg) in the dentate gyrus (DG). While LY379268 (1-3 mg/kg) reduced ketamine-evoked hyperlocomotion (12 mg/kg), it could not restore ketamine-evoked PPI deficits (4-12 mg/kg). In the DG we found that ketamine decreased Glu and DA levels, as well as HIAA/5-HT turnover, and that LY379268 could prevent ketamine effects on Glu level but not on monoamine transmission. These results may indicate that the inability of LY379268 to reverse PPI deficits is attributable to its lack of effect on ketamine-induced changes in monoamine transmission, but that LY379268 can prevent ketamine-evoked changes in glutamate, which is sufficient to block hyperlocomotion. In addition to the partial effectiveness of LY379268 in the ketamine model of schizophrenia, we observed a dual effect of LY379268 on anxious states, whereby a low dose of this compound (1 mg/kg) produced anxiolytic effects, while a higher dose (3 mg/kg) appeared to be anxiogenic. Additional work is needed to address a possible role of LY379268 in schizophrenia and anxiety treatment.
    Pharmacology Biochemistry and Behavior 08/2006; 84(3):392-9. · 2.61 Impact Factor
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    ABSTRACT: The present dose-response study sought to determine the effects of subanesthetic dosages (4-16 mg/kg) of ketamine on locomotion, sensorimotor gating (PPI), working memory, as well as c-fos expression in various limbic regions implicated in the pathogenesis of schizophrenia. In addition, we examined whether ketamine-induced locomotion was influenced by the dark/light cycle. We found that ketamine increased locomotor activity in a dose dependent manner, but found no influence of the dark-light cycle. Additionally, ketamine dose-dependently interrupted PPI, resulting in prepulse facilitation at doses of 8 and 12 mg/kg. The dose of 12 mg/kg also induced impairments in working memory assessed by the discrete-trial delayed-alternation task. C-fos expression indicated that the dose-dependent behavioral effects of ketamine might be related to changes in the activity of limbic regions, notably hippocampus and amygdala.
    Brain Research Bulletin 05/2006; 69(3):338-45. · 2.94 Impact Factor
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    ABSTRACT: In the field of computational chemistry it is usual to have only a partial set of structural information about compounds, like the connectivity or the formula. Individual studies can easily be performed using ‘human interfaces’ for building input structures. However, automatic, ‘batch’ processes cannot be applied on a large number of molecules if they imply human intervention. Studies, like QSAR, pharamacophore analysis, reaction prediction might need full, complete 3D information for the compounds of interest. The widespread tools used for structure determination (force-fields or quantum chemical methods) even require a complete set of initial 3D coordinates.Our approach intends on generating globally valid set of 3D coordinates for small and medium sized molecules, based on local structural criteria. Over against iterative, backtrack based structure predicting algorithms, our method is capable of satisfying partially inconsistent requirements. Such situations are common for structures holding polycyclic, rigid details.Goals mentioned above can be achieved using coordinates interpreted in a space with a Minkowski metric. Our coordinate assignment process is divided into the following parts: (I) Automatic generation of distance criteria based on chemically relevant local properties, such as bond stretches, bond angles, dihedral angles, etc. (II) Multi-dimensional coordinate assignment which fulfills all the criteria. (III) Geometry optimization using a force field extended to the multi-dimensional Minkowski space. The optimization eliminates the over-3D components and yields the 3D coordinates.
    Journal of Molecular Structure THEOCHEM s 666–667:51–59. · 1.37 Impact Factor
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Publication Stats

133 Citations
23.55 Total Impact Points

Institutions

  • 2011
    • ChemAxon
      Budapeŝto, Budapest, Hungary
  • 2009
    • Eötvös Loránd University
      Budapeŝto, Budapest, Hungary
  • 2007
    • Gedeon Richter Plc
      Budapeŝto, Budapest, Hungary
  • 2006
    • University of Groningen
      • Department of Psychiatry
      Groningen, Province of Groningen, Netherlands