Combined ligand- and receptor-based virtual screening methodology to identify structurally diverse PTP1B inhibitors.
A new article published at ChemMedChem by the Cheminformatics & Nutrition Group
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.
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