Articles producció científica> Bioquímica i Biotecnologia

Combined Ligand- and Receptor-Based Virtual Screening Methodology to Identify Structurally Diverse Protein Tyrosine Phosphatase 1B Inhibitors

  • Datos identificativos

    Identificador: imarina:5132284
    Autores:
    Gimeno, AleixArdid-Ruiz, AndreaJose Ojeda-Montes, MariaTomas-Hernandez, SarahCereto-Massague, AdriaBeltran-Debon, RaulMulero, MiquelValls, CristinaAragones, GerardSuarez, ManuelPujadas, GerardGarcia-Vallve, Santiago
    Resumen:
    Protein tyrosine phosphatase 1B (PTP1B) is a potential drug target for diabetes and obesity. However, designing PTP1B inhibitors that combine potency and bioavailability is a great challenge and new leads are needed to circumvent this problem. Virtual screening (VS) workflows can be used to find new PTP1B inhibitors with little chemical similarity to existing ones. Unfortunately, previous VS workflows for the identification of PTP1B inhibitors have several limitations, such as a small number of experimentally tested compounds and the low bioactivity of those compounds. We developed a VS workflow capable of identifying 15 structurally diverse PTP1B inhibitors from 20 compounds whose bioactivity was tested in vitro. Moreover, we have identified the two PTP1B inhibitors with the highest bioactivity reported by any VS (i.e. IC50 values of 1.4 and 2.1 μM), which can potentially be used as new lead compounds.
  • Otros:

    Autor según el artículo: Gimeno, Aleix; Ardid-Ruiz, Andrea; Jose Ojeda-Montes, Maria; Tomas-Hernandez, Sarah; Cereto-Massague, Adria; Beltran-Debon, Raul; Mulero, Miquel; Valls, Cristina; Aragones, Gerard; Suarez, Manuel; Pujadas, Gerard; Garcia-Vallve, Santiago
    Departamento: Bioquímica i Biotecnologia
    Autor/es de la URV: Aragonès Bargalló, Gerard / ARDID RUIZ, ANDREA / Beltrán Debón, Raúl Alejandro / Cereto Massagué, Adrián José / Garcia Vallve, Santiago / Mulero Abellán, Miguel / OJEDA MONTES, Mª JOSÉ / Pujadas Anguiano, Gerard / Suárez Recio, Manuel / TOMAS HERNÁNDEZ, SARA / Valls Bautista, Cristina
    Palabras clave: Virtual screening Type 2 diabetes mellitus Structure-activity relationship Protein tyrosine phosphatase, non-receptor type 1 Protein tyrosine phosphatase Obesity Molecular structure Models, molecular Ligands Inhibitors Humans Enzyme inhibitors Drug evaluation, preclinical Dose-response relationship, drug type 2 diabetes mellitus protein tyrosine phosphatase obesity inhibitors
    Resumen: Protein tyrosine phosphatase 1B (PTP1B) is a potential drug target for diabetes and obesity. However, designing PTP1B inhibitors that combine potency and bioavailability is a great challenge and new leads are needed to circumvent this problem. Virtual screening (VS) workflows can be used to find new PTP1B inhibitors with little chemical similarity to existing ones. Unfortunately, previous VS workflows for the identification of PTP1B inhibitors have several limitations, such as a small number of experimentally tested compounds and the low bioactivity of those compounds. We developed a VS workflow capable of identifying 15 structurally diverse PTP1B inhibitors from 20 compounds whose bioactivity was tested in vitro. Moreover, we have identified the two PTP1B inhibitors with the highest bioactivity reported by any VS (i.e. IC50 values of 1.4 and 2.1 μM), which can potentially be used as new lead compounds.
    Áreas temáticas: Saúde coletiva Química Pharmacology, toxicology and pharmaceutics (miscellaneous) Pharmacology, toxicology and pharmaceutics (all) Pharmacology & pharmacy Pharmacology Organic chemistry Odontología Molecular medicine Medicina ii Medicina i Materiais Interdisciplinar General pharmacology, toxicology and pharmaceutics General medicine Farmacia Drug discovery Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Ciências ambientais Chemistry, medicinal Biotecnología Biochemistry
    Acceso a la licencia de uso: https://creativecommons.org/licenses/by/3.0/es/
    ISSN: 18607179
    Direcció de correo del autor: adrianjose.cereto@urv.cat cristina.valls@urv.cat manuel.suarez@urv.cat miquel.mulero@urv.cat gerard.aragones@urv.cat santi.garcia-vallve@urv.cat gerard.pujadas@urv.cat raul.beltran@urv.cat
    Identificador del autor: 0000-0001-5583-5695 0000-0003-0122-8253 0000-0002-0348-7497 0000-0003-2598-8089 0000-0001-9691-1906
    Fecha de alta del registro: 2024-09-07
    Versión del articulo depositado: info:eu-repo/semantics/acceptedVersion
    Enlace a la fuente original: https://chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/cmdc.201800267
    URL Documento de licencia: https://repositori.urv.cat/ca/proteccio-de-dades/
    Referencia al articulo segun fuente origial: Chemmedchem. 13 (18): 1939-1948
    Referencia de l'ítem segons les normes APA: Gimeno, Aleix; Ardid-Ruiz, Andrea; Jose Ojeda-Montes, Maria; Tomas-Hernandez, Sarah; Cereto-Massague, Adria; Beltran-Debon, Raul; Mulero, Miquel; Vall (2018). Combined Ligand- and Receptor-Based Virtual Screening Methodology to Identify Structurally Diverse Protein Tyrosine Phosphatase 1B Inhibitors. Chemmedchem, 13(18), 1939-1948. DOI: 10.1002/cmdc.201800267
    DOI del artículo: 10.1002/cmdc.201800267
    Entidad: Universitat Rovira i Virgili
    Año de publicación de la revista: 2018
    Tipo de publicación: Journal Publications
  • Palabras clave:

    Biochemistry,Chemistry, Medicinal,Drug Discovery,Molecular Medicine,Organic Chemistry,Pharmacology,Pharmacology & Pharmacy,Pharmacology, Toxicology and Pharmaceutics (Miscellaneous)
    Virtual screening
    Type 2 diabetes mellitus
    Structure-activity relationship
    Protein tyrosine phosphatase, non-receptor type 1
    Protein tyrosine phosphatase
    Obesity
    Molecular structure
    Models, molecular
    Ligands
    Inhibitors
    Humans
    Enzyme inhibitors
    Drug evaluation, preclinical
    Dose-response relationship, drug
    type 2 diabetes mellitus
    protein tyrosine phosphatase
    obesity
    inhibitors
    Saúde coletiva
    Química
    Pharmacology, toxicology and pharmaceutics (miscellaneous)
    Pharmacology, toxicology and pharmaceutics (all)
    Pharmacology & pharmacy
    Pharmacology
    Organic chemistry
    Odontología
    Molecular medicine
    Medicina ii
    Medicina i
    Materiais
    Interdisciplinar
    General pharmacology, toxicology and pharmaceutics
    General medicine
    Farmacia
    Drug discovery
    Ciências biológicas iii
    Ciências biológicas ii
    Ciências biológicas i
    Ciências ambientais
    Chemistry, medicinal
    Biotecnología
    Biochemistry
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