Search results for "polypharmacology"
showing 6 items of 6 documents
Kinase Inhibitors in Multitargeted Cancer Therapy
2017
The old-fashioned anticancer approaches, aiming in arresting cancer cell proliferation interfering with non-specific targets (e.g. DNA), have been replaced, in the last decades, by more specific target oriented ones. Nonetheless, single-target approaches have not always led to optimal outcomes because, for its complexity, cancer needs to be tackled at various levels by modulation of several targets. Although at present, combinations of individual single-target drugs represent the most clinically practiced therapeutic approaches, the modulation of multiple proteins by a single drug, in accordance with the polypharmacological strategy, has become more and more appealing. In the perspective of…
Drugs Polypharmacology by in Silico Methods: New Opportunities in Drug Discovery
2016
Background Polypharmacology, defined as the modulation of multiple proteins rather than a single target to achieve a desired therapeutic effect, has been gaining increasing attention since 1990s, when industries had to withdraw several drugs due to their adverse effects, leading to permanent injuries or death, with multi-billiondollar legal damages. Therefore, if up to then the "one drug one target" paradigm had seen many researchers interest focused on the identification of selective drugs, with the strong expectation to avoid adverse drug reactions (ADRs), very recently new research strategies resulted more appealing even as attempts to overcome the decline in productivity of the drug dis…
Strategies to gain novel Alzheimer’s disease diagnostics and therapeutics using modulators of ABCA transporters
2021
Adenosine-triphosphate-(ATP)-binding cassette (ABC) transport proteins are ubiquitously present membrane-bound efflux pumps that distribute endo- and xenobiotics across intra- and intercellular barriers. Discovered over 40 years ago, ABC transporters have been identified as key players in various human diseases, such as multidrug-resistant cancer and atherosclerosis, but also neurodegenerative diseases, such as Alzheimer���s disease (AD). Most prominent and well-studied are ABCB1, ABCC1, and ABCG2, not only due to their contribution to the multidrug resistance (MDR) phenotype in cancer, but also due to their contribution to AD. However, our understanding of other ABC transporters is limited…
Binding mode analysis of ABCA7 for the prediction of novel Alzheimer's disease therapeutics
2021
Graphical abstract
Multi or Single-Kinase Inhibitors to Counteract Drug Resistance in Cancer: What is New?
2023
The concept of protein kinase inhibition starts from the groundbreaking research on the role of these proteins in the regulation of fundamental processes, including proliferation, cell cycle, apoptosis, metabolism, and inflammation. Kinase genetic mutations, as well as overexpression and dysregulation, can contribute to the development of several diseases, including neoplasms, leading to relapses and resistance to standard drug chemotherapy [1-3].
DRUDIT: Web-based DRUgs DIscovery Tools to design small molecules as modulators of biological targets
2019
Abstract Motivation New in silico tools to predict biological affinities for input structures are presented. The tools are implemented in the DRUDIT (DRUgs DIscovery Tools) web service. The DRUDIT biological finder module is based on molecular descriptors that are calculated by the MOLDESTO (MOLecular DEScriptors TOol) software module developed by the same authors, which is able to calculate more than one thousand molecular descriptors. At this stage, DRUDIT includes 250 biological targets, but new external targets can be added. This feature extends the application scope of DRUDIT to several fields. Moreover, two more functions are implemented: the multi- and on/off-target tasks. These tool…