META. 1. A Program for the Evaluation of Metabolic Transformation of Chemicals

Klopman, Gilles; Dimayuga, Mario; Talafous, Joseph

doi:10.1021/ci00022a014

Cited by 146 publications

(78 citation statements)

References 3 publications

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“…QSAR has been applied successfully and extensively to ind predictive models for activity of bioactive agents for the toxicity prediction [26][27][28][29], activity of peptides [30][31][32][33], drug metabolism [34][35][36], gastrointestinal absorption [37][38][39], prediction of pharmacokinetic and ADME properties [40][41][42][43][44], drug resistance and physicochemical properties [45][46][47].…”

Section: Quantitative Structure Activity Relationshipmentioning

confidence: 99%

Introductory Chapter: Some Quantitative Structure Activity Relationship Descriptor

Kandemirli¹

2017

Quantitative Structure-Activity Relationship

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Section: Quantitative Structure Activity Relationshipmentioning

confidence: 99%

Introductory Chapter: Some Quantitative Structure Activity Relationship Descriptor

Kandemirli¹

2017

Quantitative Structure-Activity Relationship

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Section: In Silico Computational Toolsmentioning

confidence: 99%

“…A given compound is fragmented and then passed through all rules to identify putative metabolically labile sites. Expert systems and their databases, such as MetabolExpert (Darvas, 1988), META (Klopman, Dimayuga, Talafous, 1994), METEOR (Testa et al, 2005), MetaDrug (Ekins et al, 2006), and PK/DB (Moda et al, 2008), are examples of in silico methods used to predict drug biotransformation pathways and possible metabolites, that provide a ranked list of most likely metabolites.Metasite (Cruciani et al, 2005) is a computational program for metabolite formation prediction, which combines structural information, by matching the structural complementarity of the substrate and the protein, and rule-based and reactivity methods.The availability of more and more 3D protein structures of P450 paves the way for molecular modeling approaches that zoom in on the atomic details of enzymeligand interactions. Docking is the most commonly used structure-based method, able to predict the site of metabolism of the substrate based on which atoms are exposed or close to the catalytic centre (the heme iron) in order for metabolism to take place (Stjernschantz, Vermeulen, Oostenbrink, 2008).…”

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confidence: 99%

Twenty-six years of HIV science: an overview of anti-HIV drugs metabolism

Andrade

Freitas

Oliveira

2011

Braz. J. Pharm. Sci.

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From the identification of HIV as the agent causing AIDS, to the development of effective antiretroviral drugs, the scientific achievements in HIV research over the past twenty-six years have been formidable. Currently, there are twenty-five anti-HIV compounds which have been formally approved for clinical use in the treatment of AIDS. These compounds fall into six categories: nucleoside reverse transcriptase inhibitors (NRTIs), nucleotide reverse transcriptase inhibitors (NtRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), cell entry inhibitors or fusion inhibitors (FIs), co-receptor inhibitors (CRIs), and integrase inhibitors (INIs). Metabolism by the host organism is one of the most important determinants of the pharmacokinetic profile of a drug. Formation of active or toxic metabolites will also have an impact on the pharmacological and toxicological outcomes. Therefore, it is widely recognized that metabolism studies of a new chemical entity need to be addressed early in the drug discovery process. This paper describes an overview of the metabolism of currently available anti-HIV drugs.Uniterms: AIDS/treatment. Drugs/anti-HIV. Drugs/metabolism. Antiretroviral drugs. Biotransformation.Da identificação do HIV como o agente causador da AIDS, ao desenvolvimento de fármacos antirretrovirais eficazes, os avanços científicos na pesquisa sobre o HIV nos últimos vinte e seis anos foram marcantes. Atualmente, existem vinte e cinco fármacos anti-HIV formalmente aprovados pelo FDA para utilização clínica no tratamento da AIDS. Estes compostos são divididos em seis classes: inibidores nucleosídeos de transcriptase reversa (INTR), inibidores nucleotídeos de transcriptase reversa (INtTR), inibidores não-nucleosídeos de transcriptase reversa (INNTR), inibidores de protease (IP), inibidores da entrada celular ou inibidores de fusão (IF), inibidores de co-receptores (ICR) e inibidores de integrase (INI). O metabolismo consiste em um dos maiores determinantes do perfil farmacocinético de um fármaco. A formação de metabólitos ativos ou tóxicos terá impacto nas respostas farmacológicas ou toxicológicas do fármaco. Portanto, é amplamente reconhecido que estudos do metabolismo de uma nova entidade química devem ser realizados durante as fases iniciais do processo de desenvolvimento de fármacos. Este artigo descreve uma abordagem do metabolismo dos fármacos anti-HIV atualmente disponíveis na terapêutica.Unitermos: AIDS/tratamento. Fármacos/anti-HIV. Fármacos/antirretrovirais. Fármacos/metabolismo. Biotransformação. INTRODUCTIONThe human immunodeficiency virus (HIV) has been established as the causative agent of the acquired immunodeficiency syndrome (AIDS) for over twentysix years now (Barré-Sinoussi et al., 1983). During this time, an unprecedented success has been achieved in discovering anti-HIV drugs as reflected by the fact that there are now more drugs approved for the treatment of HIV than for all other viral infections put together (Mehellou, De Clercq, 2009). Despite this progress...

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“…Для своей работы система использует алгоритм программы PASS. Среди других экспертных систем надо отметить программы TIMES [40], METEOR [41], META [42].…”

Section: рисунокunclassified

Computer-based substrate specifity prediction for cytochrome P450

et al. 2010

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Cytochrome P450 is important class of enzymes metabolizing numerous drugs. The composition and activity of these enzymes are determined the drug distribution in organism, its pharmacological and toxic effect. Thus the prediction of the behaviour of compounds in organism is essential for discovery and development of new drugs in the early stages of this process. The different isoforms of cytochrome P450 can oxidized wide range of chemical compounds and their substrate specifity do not correlate with their taxonomical classification. The main methods of cytochrome P450 substrate specifity prediction is reviewed. These methods divided based on primary informations that used: prediction based on amino acid sequences, ligand-based (pharmacophore and QSAR models) and structure-based (molecular docking, affinity prediction) methods. The common problem of cytochrome P450 substrate prediction and advantage and disadvantages of these methods are discussed.

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META. 1. A Program for the Evaluation of Metabolic Transformation of Chemicals

Cited by 146 publications

References 3 publications

Introductory Chapter: Some Quantitative Structure Activity Relationship Descriptor

Introductory Chapter: Some Quantitative Structure Activity Relationship Descriptor

Twenty-six years of HIV science: an overview of anti-HIV drugs metabolism

Computer-based substrate specifity prediction for cytochrome P450

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