FAF-Drugs: free ADME/tox filtering of compound collections

Miteva, Maria A.; Violas, Stephanie; Montès, Matthieu; Gomez, David; Tufféry, Pierre; Villoutreix, Bruno O.

doi:10.1093/nar/gkl065

Cited by 125 publications

(86 citation statements)

References 47 publications

(27 reference statements)

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“…Absorption, distribution, metabolism, and excretion/tox filtering was performed with Filter (OpenEye Scientific Software, Santa Fe, NM) and FAF-Drugs (41). The remaining 304,000 molecules were docked by using the rigid-body docking package FRED (OpenEye Scientific Software) into the closed (PDE ID code 1CZV) and open crystal (PDE ID code 1CZT or 1CZS) forms of the FV C2 domain.…”

Section: Methodsmentioning

confidence: 99%

Design of protein–membrane interaction inhibitors by virtual ligand screening, proof of concept with the C2 domain of factor V

Segers

Spérandio

Sack

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Most orally bioavailable drugs on the market are competitive inhibitors of catalytic sites, but a significant number of targets remain undrugged, because their molecular functions are believed to be inaccessible to drug-like molecules. This observation specifically applies to the development of small-molecule inhibitors of macromolecular interactions such as protein-membrane interactions that have been essentially neglected thus far. Nonetheless, many proteins containing a membrane-targeting domain play a crucial role in health and disease, and the inhibition of such interactions therefore represents a very promising therapeutic strategy. In this study, we demonstrate the use of combined in silico structure-based virtual ligand screening and surface plasmon resonance experiments to identify compounds that specifically disrupt protein-membrane interactions. Computational analysis of several membrane-binding domains revealed they all contain a druggable pocket within their membrane-binding region. We applied our screening protocol to the second discoidin domain of coagulation factor V and screened >300,000 drug-like compounds in silico against two known crystal structure forms. For each C2 domain structure, the top 500 molecules predicted as likely factor V-membrane inhibitors were evaluated in vitro. Seven drug-like hits were identified, indicating that therapeutic targets that bind transiently to the membrane surface can be investigated costeffectively, and that inhibitors of protein-membrane interactions can be designed.computational chemistry ͉ discoidin domain ͉ surface plasmon resonance

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Section: Methodsmentioning

confidence: 99%

Design of protein–membrane interaction inhibitors by virtual ligand screening, proof of concept with the C2 domain of factor V

Segers

Spérandio

Sack

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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“…Lipinski rule: Each possible drug must comply with several basic criteria, such as its low production cost, be soluble, stable, but must also comply with scales associated with its pharmacological properties of absorption, distribution, metabolism, Excretion and toxicity (ADME-T) [9]. This method is based essentially on Lipinski's rule 5 [10,11] Calculation of interactions "enzyme-similar": To study the interactions between the MetAP2 enzyme and the similar we use a specific PubChem library.…”

Section: Inhibition Of 5jfr By Flex Xmentioning

confidence: 99%

Use of molecular docking in the search for new anti-angiogenic agents

Boucherit¹,

Zouaghi²,

Sara³

et al. 2017

Cancer Rep Rev

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Angiogenesis, the growth of new blood capillaries from preexisting vessels, is a crucial process in the development and spread of cancers. The inhibition of angiogenesis thus appears as a promising therapy for cancer. Methionine aminopeptidase type 2 (MetAP2) is a metallo-enzyme considered today as an attractive target for the fight against cancer because its inhibition blocks the process of angiogenesis and therefore tumor progression. The aim of this work is to study the inhibition of MetAP II by molecular docking methods in order to discover new anti-angiogenic agents. FlexX is the molecular docking program used. Thus, this software allows predicting protein-inhibitor interactions. It was used to study the inhibition of 5JFR, a human MetAP II, by various molecules in order to discover the best inhibitors of this enzyme. The evaluation of the interaction energy of these inhibitors made it possible to identify those exhibiting the best inhibitory effect. These are compounds 6KP and A84, whose docking scores are -32.33 and -32.92 Kj/mol, respectively. The virtual screening of a similar collection of 370 of the compound 6KP and 139 of the compound A84 from PubChem revealed the compounds CID_66896495 and CID_11740546 as best inhibitors of MetAP II with an interaction energy equal to -40.27 KJ / mol for the first and -35.93 Kj / mol for the second. Finally, the Lipinski rule was performed to verify the pharmacokinetic properties of these two similar; they fit perfectly within the margin of the criteria imposed by Lipinski.

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“…Los fármacos ingresan al organismo generalmente vía oral, y el o los principios activos que contiene el fármaco, es o son expuesto(s) para su absorción en el intestino delgado, a través de las vellosidades que éste posee, después que los jugos gástricos del estómago han realizado su trabajo de liberarlos. Cuando el medicamento ya se encuentra en el torrente sanguíneo, éste se distribuye, metaboliza y elimina (Miteva et al, 2006).…”

Section: Persistencia De Principios Activos Farmacéuticos En El Aguaunclassified

Contaminantes Emergentes en Aguas: Metabolitos de Fármacos. Una Revisión.

Tejada

Quiñonez

Peña

2014

Rev. Fac. Cienc. Básicas

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<p class="Default">El medio ambiente acuático se ha visto afectado en gran medida por los residuos provenientes de compuestos farmacéuticos, estos no solo afectan los procesos biológicos utilizados para el tratamiento de aguas residuales municipales, sino que también sobrepasan los límites de la potabilización. El objetivo de este artículo es realizar una revisión acerca de los aspectos de consideración con respecto a esta problemática, además las características físico químicas, y su detección en el agua, refiriéndose a esto último no solo como la identificación de estos contaminantes sino también la proporción de ello. En este contexto se discuten las limitaciones que se llevan a cabo con el cuidado de los cuerpos de agua no solo en la disposición de aguas residuales sino también del consumo humano.</p>

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FAF-Drugs: free ADME/tox filtering of compound collections

Cited by 125 publications

References 47 publications

Design of protein–membrane interaction inhibitors by virtual ligand screening, proof of concept with the C2 domain of factor V

Design of protein–membrane interaction inhibitors by virtual ligand screening, proof of concept with the C2 domain of factor V

Use of molecular docking in the search for new anti-angiogenic agents

Contaminantes Emergentes en Aguas: Metabolitos de Fármacos. Una Revisión.

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