Although science and technology have progressed rapidly, de novo drug development has been a costly and time-consuming process over the past decades. In this scenario, drug repurposing has appeared as an alternative tool to accelerate the drug development process. Herein, we applied such an approach to the highly popular human Carbonic Anhydrase (hCA) VA drug target, that is involved in ureagenesis, gluconeogenesis, lipogenesis, and in the metabolism regulation. Albeit several hCA inhibitors have been designed and are currently in clinical use, serious drug interactions have been reported due to their poor selectivity. In this perspective, the drug repurposing approach could be a useful tool for investigating the drug promiscuity/polypharmacology profile. In this chapter, we describe a combination of virtual screening techniques and in vitro assays aimed to identify novel selective hCA VA inhibitors and to repurpose drugs known for other clinical indications.

From Homology Modeling to the Hit Identification and Drug Repurposing: A Structure-Based Approach in the Discovery of Novel Potential Anti-Obesity Compounds

Artese, Anna;Ortuso, Francesco;Alcaro, Stefano
2021-01-01

Abstract

Although science and technology have progressed rapidly, de novo drug development has been a costly and time-consuming process over the past decades. In this scenario, drug repurposing has appeared as an alternative tool to accelerate the drug development process. Herein, we applied such an approach to the highly popular human Carbonic Anhydrase (hCA) VA drug target, that is involved in ureagenesis, gluconeogenesis, lipogenesis, and in the metabolism regulation. Albeit several hCA inhibitors have been designed and are currently in clinical use, serious drug interactions have been reported due to their poor selectivity. In this perspective, the drug repurposing approach could be a useful tool for investigating the drug promiscuity/polypharmacology profile. In this chapter, we describe a combination of virtual screening techniques and in vitro assays aimed to identify novel selective hCA VA inhibitors and to repurpose drugs known for other clinical indications.
978-1-0716-1208-8
978-1-0716-1209-5
Anti-obesity drugs
Carbonic anhydrase VA
Drug design
Drug repurposing
Molecular docking
Selectivity
Virtual screening
Anti-Obesity Agents
Carbonic Anhydrase Inhibitors
Drug Design
Drug Repositioning
In Vitro Techniques
Ligands
Models, Chemical
Molecular Docking Simulation
Molecular Dynamics Simulation
Molecular Structure
Small Molecule Libraries
Software
Structure-Activity Relationship
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.12317/81029
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