Author, as appears in the article.: 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
Department: Bioquímica i Biotecnologia
URV's Author/s: 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
Keywords: 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
Abstract: 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.
Thematic Areas: 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
licence for use: https://creativecommons.org/licenses/by/3.0/es/
ISSN: 18607179
Author's mail: 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
Author identifier: 0000-0001-5583-5695 0000-0003-0122-8253 0000-0002-0348-7497 0000-0003-2598-8089 0000-0001-9691-1906
Record's date: 2024-09-07
Papper version: info:eu-repo/semantics/acceptedVersion
Link to the original source: https://chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/cmdc.201800267
Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
Papper original source: Chemmedchem. 13 (18): 1939-1948
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
Article's DOI: 10.1002/cmdc.201800267
Entity: Universitat Rovira i Virgili
Journal publication year: 2018
Publication Type: Journal Publications
Repositori URV