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 Ptpn1 protein, human 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: 2024-11-23
Versión del articulo depositado: info:eu-repo/semantics/acceptedVersion
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
Entidad: Universitat Rovira i Virgili
Año de publicación de la revista: 2018
Tipo de publicación: Journal Publications
Repositori URV