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Start Over Author "Mandrup Bertozzi S" Topic drug design
2 results on '"Mandrup Bertozzi S"'

1. Multitarget Compounds for Bipolar Disorder: From Rational Design to Preliminary Pharmacokinetic Evaluation.

Author

Di Martino RMC, Bottegoni G, Seghetti F, Russo D, Penna I, De Simone A, Ottonello G, Mandrup Bertozzi S, Armirotti A, Bandiera T, Belluti F, and Cavalli A

Subjects
Antipsychotic Agents chemical synthesis, Antipsychotic Agents chemistry, Bipolar Disorder metabolism, Dose-Response Relationship, Drug, Glycogen Synthase Kinase 3 beta antagonists & inhibitors, Glycogen Synthase Kinase 3 beta metabolism, Humans, Molecular Structure, Receptors, Dopamine D3 agonists, Receptors, Dopamine D3 metabolism, Structure-Activity Relationship, Antipsychotic Agents pharmacokinetics, Bipolar Disorder drug therapy, Drug Design
Abstract

Due to the complex and multifactorial nature of bipolar disorder (BD), single-target drugs have traditionally provided limited relief with no disease-modifying effects. In line with the polypharmacology paradigm, we attempted to overcome these limitations by devising two series of multitarget-directed ligands endowed with both a partial agonist profile at dopamine receptor D3 (D3R) and inhibitory activity against glycogen synthase kinase 3 beta (GSK-3β). These are two structurally unrelated targets that play independent, yet connected, roles in cognition and mood regulation. Two compounds (7 and 10) emerged as promising D3R/GSK-3β multitarget-directed ligands with nanomolar activity at D3R and low-micromolar inhibition of GSK-3β, thereby confirming, albeit preliminarily, the feasibility of our strategy. Furthermore, 7 showed promising drug-like properties in stability and pharmacokinetic studies., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Published
2020
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2. Multitarget Compounds for Bipolar Disorder: From Rational Design to Preliminary Pharmacokinetic Evaluation

Author

Giuliana Ottonello, Sine Mandrup Bertozzi, Francesca Seghetti, Tiziano Bandiera, Andrea Cavalli, Debora Russo, Ilaria Penna, Alessio De Simone, Rita Maria Concetta Di Martino, Giovanni Bottegoni, Andrea Armirotti, Federica Belluti, Di Martino R.M.C., Bottegoni G., Seghetti F., Russo D., Penna I., De Simone A., Ottonello G., Mandrup Bertozzi S., Armirotti A., Bandiera T., Belluti F., and Cavalli A.

Subjects
Bipolar Disorder, enzymes, receptors, Pharmacology, 01 natural sciences, Biochemistry, Partial agonist, drug discovery, Structure-Activity Relationship, Pharmacokinetics, Dopamine receptor D3, Drug Discovery, medicine, Humans, Bipolar disorder, General Pharmacology, Toxicology and Pharmaceutics, Receptor, GSK3B, polypharmacology, Glycogen Synthase Kinase 3 beta, Dose-Response Relationship, Drug, Molecular Structure, 010405 organic chemistry, Drug discovery, Chemistry, molecular modeling, Organic Chemistry, Receptors, Dopamine D3, Rational design, medicine.disease, 0104 chemical sciences, enzyme, 010404 medicinal & biomolecular chemistry, Drug Design, Molecular Medicine, Antipsychotic Agents
Abstract

Due to the complex and multifactorial nature of bipolar disorder (BD), single-target drugs have traditionally provided limited relief with no disease-modifying effects. In line with the polypharmacology paradigm, we attempted to overcome these limitations by devising two series of multitarget-directed ligands endowed with both a partial agonist profile at dopamine receptor D3 (D3R) and inhibitory activity against glycogen synthase kinase 3 beta (GSK-3β). These are two structurally unrelated targets that play independent, yet connected, roles in cognition and mood regulation. Two compounds (7 and 10) emerged as promising D3R/GSK-3β multitarget-directed ligands with nanomolar activity at D3R and low-micromolar inhibition of GSK-3β, thereby confirming, albeit preliminarily, the feasibility of our strategy. Furthermore, 7 showed promising drug-like properties in stability and pharmacokinetic studies.

Published
2020

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