Drug discovery today
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Drug discovery today · Feb 2021
ReviewExpanded Access Programs, compassionate drug use, and Emergency Use Authorizations during the COVID-19 pandemic.
The US Food and Drug Administration (FDA) Expanded Access (EA) Program, which allows for compassionate uses of unapproved therapeutics and diagnostics outside of clinical trials, has gained significant traction during the Coronavirus 2019 (COVID-19) pandemic. While development of vaccines has been the major focus, uncertainties around new vaccine safety and effectiveness have spawned interest in other pharmacological options. ⋯ Here, we review the US experience in 2020 with pharmacological EA and EUA approvals during the pandemic. We also provide a description of, and clinical rationale for, each of the EA- or EUA-approved drugs (e.g. remdesivir, convalescent plasma, propofol 2%, hydroxychloroquine, ruxolitinib, bamlanivimab, baricitinib, casirivimab plus imdevimab) during the pandemic and concluding reflections on the EA program and its potential future uses.
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly become a global health pandemic. The lack of effective treatments, coupled with its etiology, has resulted in more than 400,000 deaths at the time of writing. ⋯ However, several avenues remain unexplored, including disrupting E and M protein oligomerization, outcompeting host glycan-virus interactions, interfering with the heparan sulfate proteoglycans-virus interaction, and others. In this review, we highlight some of these opportunities while summarizing the drugs currently in use against coronavirus 2019 (COVID-19).
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Drug discovery today · Oct 2019
ReviewDrug repurposing: a promising tool to accelerate the drug discovery process.
Traditional drug discovery and development involves several stages for the discovery of a new drug and to obtain marketing approval. It is necessary to discover new strategies for reducing the drug discovery time frame. Today, drug repurposing has gained importance in identifying new therapeutic uses for already-available drugs. ⋯ Numerous strategies to discover new indications for FDA-approved drugs are discussed in this article. Drug repurposing has therefore become a productive approach for drug discovery because it provides a novel way to explore old drugs for new use but encounters several challenges. Some examples of different approaches are reviewed here.
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Chemoinformatics is an established discipline focusing on extracting, processing and extrapolating meaningful data from chemical structures. With the rapid explosion of chemical 'big' data from HTS and combinatorial synthesis, machine learning has become an indispensable tool for drug designers to mine chemical information from large compound databases to design drugs with important biological properties. To process the chemical data, we first reviewed multiple processing layers in the chemoinformatics pipeline followed by the introduction of commonly used machine learning models in drug discovery and QSAR analysis. Here, we present basic principles and recent case studies to demonstrate the utility of machine learning techniques in chemoinformatics analyses; and we discuss limitations and future directions to guide further development in this evolving field.
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Drug discovery today · Aug 2018
ReviewN-acylethanolamine hydrolyzing acid amidase inhibition: tools and potential therapeutic opportunities.
N-acylethanolamines (NAEs) (e.g., N-palmitoylethanolamine, N-arachidonoylethanolamine, N-oleoylethanolamine) are bioactive lipids involved in many physiological processes including pain, inflammation, anxiety, cognition and food intake. Two enzymes are responsible for the hydrolysis of NAEs and therefore regulate their endogenous levels and effects: fatty acid amide hydrolase (FAAH) and N-acylethanolamine-hydrolyzing acid amidase (NAAA). ⋯ An increasing number of studies describe the synthesis and pharmacological characterization of NAAA inhibitors. Recent medicinal chemistry efforts have led to the development of potent and stable inhibitors that enable studying the effects of NAAA inhibition in preclinical disease models, notably in the context of pain and inflammation.