Author, as appears in the article.: Gimeno A, Ardid-Ruiz A, Ojeda-Montes M, Tomás-Hernández S, Cereto-Massagué A, Beltrán-Debón R, Mulero M, Valls C, Aragonès G, Suárez M, Pujadas G, Garcia-Vallvé S

Department: Bioquímica i Biotecnologia

URV's Author/s: Aragonès Bargalló, Gerard / Beltrán Debón, Raúl Alejandro / Cereto Massagué, Adrián José / Garcia Vallve, Santiago / Mulero Abellán, Miguel / Pujadas Anguiano, Gerard / Suárez Recio, Manuel / TOMAS HERNÁNDEZ, SARA / Valls Bautista, Cristina

Keywords: Virtual screening Type 2 diabetes mellitus Protein tyrosine phosphatase Obesity Inhibitors 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: gerard.aragones@urv.cat cristina.valls@urv.cat adrianjose.cereto@urv.cat raul.beltran@urv.cat gerard.pujadas@urv.cat santi.garcia-vallve@urv.cat miquel.mulero@urv.cat manuel.suarez@urv.cat adrianjose.cereto@urv.cat

Author identifier: 0000-0001-5583-5695 0000-0001-9691-1906 0000-0003-2598-8089 0000-0002-0348-7497 0000-0003-0122-8253

Record's date: 2023-02-22

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: http://repositori.urv.cat/ca/proteccio-de-dades/

Papper original source: Chemmedchem. 13 (18): 1939-1948

APA: Gimeno A, Ardid-Ruiz A, Ojeda-Montes M, Tomás-Hernández S, Cereto-Massagué A, Beltrán-Debón R, Mulero M, Valls C, Aragonès G, Suárez M, Pujadas G, Gar (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