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 / Gimeno Vives, Aleix / 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; aleix.gimeno@urv.cat; aleix.gimeno@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
Fecha de alta del registro: 2025-03-22
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
Repositori URV