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Expert Opinion on Drug Discovery

Matthew D Breyer, Matthias Kretzler
Diabetic kidney disease (DKD) has emerged as major cause of morbidity and mortality. After progressing to renal failure, over 70% of DKD patients are dead with five years. New treatments to slow this progression are desperately needed. Areas covered: This review highlights the current treatment options for people with DKD with a particular focus on angiotensin pathway blockade and the potential use of sodium glucose linked transporter 2 (SGLT2) inhibitors. These treatments are associated with an initial decrease in glomerular filtration rate (GFR) and albuminuria; there is also attention on renal hyperfiltration as therapeutic target...
November 16, 2017: Expert Opinion on Drug Discovery
Xuewei Liu, Danfeng Shi, Shuangyan Zhou, Hongli Liu, Huanxiang Liu, Xiaojun Yao
Molecular dynamics (MD) simulations can provide not only plentiful dynamical structural information on biomacromolecules but also a wealth of energetic information about protein and ligand interactions. Such information is very important to understanding the structure-function relationship of the target and the essence of protein-ligand interactions and to guiding the drug discovery and design process. Thus, MD simulations have been applied widely and successfully in each step of modern drug discovery. Areas covered: In this review, the authors review the applications of MD simulations in novel drug discovery, including the pathogenic mechanisms of amyloidosis diseases, virtual screening and the interaction mechanisms between drugs and targets...
November 15, 2017: Expert Opinion on Drug Discovery
Bernhard Biersack, Khursheed Ahmed, Subhash Padhye, Rainer Schobert
The versatile multicomponent Mannich reaction occupies a salient position in organic chemistry and drug design. Sound knowledge of its scope and variations and of the biological activities of Mannich bases is crucial for the development and improvement of drugs for various diseases. Areas covered: The following article provides an overview of the latest developments in the field of drugs based on the Mannich reaction. Web-based literature searching tools such as PubMed and SciFinder were applied to obtain useful articles...
November 14, 2017: Expert Opinion on Drug Discovery
(no author information available yet)
No abstract text is available yet for this article.
November 9, 2017: Expert Opinion on Drug Discovery
Carolina L Bellera, Mauricio E Di Ianni, Alan Talevi
Although the therapeutic arsenal against ulcerative colitis has greatly expanded (including the revolutionary advent of biologics), there remain patients who are refractory to current medications while the safety of the available therapeutics could also be improved. Molecular topology provides a theoretic framework for the discovery of new therapeutic agents in a very efficient manner, and its applications in the field of ulcerative colitis have slowly begun to flourish. Areas covered: After discussing the basics of molecular topology, the authors review QSAR models focusing on validated targets for the treatment of ulcerative colitis, entirely or partially based on topological descriptors...
November 1, 2017: Expert Opinion on Drug Discovery
Yue Zhong, Yu-Ting Lu, Ying Sun, Zhi-Hao Shi, Nian-Guang Li, Yu-Ping Tang, Jin-Ao Duan
The overexpression of matrix metalloproteinase (MMP) plays an important role in the context of tumor invasion and metastasis, and MMP-2 has been characterized as the most validated target for cancer. Therefore, it is necessary to design matrix metalloproteinase inhibitors (MMPIs) that would be active and selective against MMP-2 but non-selective toward other MMPs. Areas covered: This article clearly describes the structural character of MMP-2 followed by a review of the recent development of selective MMP-2 inhibitors based on their basic structures...
October 31, 2017: Expert Opinion on Drug Discovery
Baihong Guo, Qiang Zhou
No abstract text is available yet for this article.
October 30, 2017: Expert Opinion on Drug Discovery
Amelia Licari, Riccardo Castagnoli, Ilaria Brambilla, Alessia Marseglia, Maria Angela Tosca, Gian Luigi Marseglia, Giorgio Ciprandi
Asthma is a chronic disease with significant heterogeneity in clinical features, disease severity, pattern of underlying disease mechanisms, and responsiveness to specific treatments. While the majority of asthmatic patients are controlled by standard pharmacological strategies, a significant subgroup has limited therapeutic options representing a major unmet need. Ongoing asthma research aims to better characterize distinct clinical phenotypes, molecular endotypes, associated reliable biomarkers, and also to develop a series of new effective targeted treatment modalities...
October 27, 2017: Expert Opinion on Drug Discovery
Jane P F Bai, Ioannis N Melas, Junguk Hur, Ellen Guo
No abstract text is available yet for this article.
October 27, 2017: Expert Opinion on Drug Discovery
Zeyad T Sahli, Frank I Tarazi
Pimavanserin is the first FDA-approved atypical antipsychotic drug indicated for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis (PDP). Areas covered: This review focuses on the preclinical discovery of pimavanserin. It analyzes the pharmacological, behavioral and molecular mechanisms of pimavanserin and their contribution to the therapeutic advantages of the drug as reported in published preclinical and clinical studies, and product labels. Expert opinion: Pimavanserin exhibits a unique pharmacological profile with nanomolar affinity at serotonin 5-HT2A and 5-HT2C receptors...
October 19, 2017: Expert Opinion on Drug Discovery
Danylo Kaminskyy, Anna Kryshchyshyn, Roman Lesyk
Rhodanines, as one of the 4-thiazolidinones subtypes, are recognized as privileged heterocycles in medicinal chemistry. The main achievements include the development of drug-like molecules with numerous biological activities as well as approved drugs. Among rhodanines, 5-ene-rhodanines are of special interest, and are often claimed as pan assay interference compounds due to Michael acceptor functionality. Areas covered: Herein, the synthetic protocols for rhodanines and their transformation are reviewed. Biological activity is briefly discussed as well as biotargets, mode of actions and optimization directions...
October 11, 2017: Expert Opinion on Drug Discovery
Silvia Maria Lavezzi, Elisa Borella, Letizia Carrara, Giuseppe De Nicolao, Paolo Magni, Italo Poggesi
Drug attrition in oncology clinical development is higher than other therapeutic areas. In this context, pharmacometric modeling represents a useful tool to explore drug efficacy in earlier phases of clinical development, anticipating overall survival using quantitative model-based metrics. Furthermore, modeling approaches can be used to characterize earlier the safety and tolerability profile of drug candidates, and, thus, the risk-benefit ratio and the therapeutic index, supporting the design of optimal treatment regimens and accelerating the whole process of clinical drug development...
October 3, 2017: Expert Opinion on Drug Discovery
Daniela Rossi, Marilù Tarantino, Giacomo Rossino, Marta Rui, Markus Juza, Simona Collina
Over the last 30 years, the scientific community has directed its efforts towards the identification of enantioselective approaches to obtain the desired active enantiomer. Accordingly, efficient production of single enantiomers from small to large scale, throughout Drug Discovery (DD) programs, has become of great interest and a fundamental challenge. Areas covered: This review focuses on two fundamental strategies for preparing enantiomers in high yields and with an excellent enantiomeric excess (ee). Separation of racemates, enantioselective synthesis procedures, and integrated approaches have been extensively reviewed, to offer a guide that enables the selection of the suitable methodology for producing pure enantiomers in scales from small to large...
October 3, 2017: Expert Opinion on Drug Discovery
Kathryn K Chadman
Autism spectrum disorder (ASD) is characterized by deficits in social communication and restricted interests/repetitive behaviors, for which there are currently no approved drug treatments. The core symptoms of ASD vary widely in severity and are often accompanied by other neuropsychiatric disorders. Drug discovery has been challenging because of the lack of understanding of the underlying pathophysiology of ASD as well as the heterogeneity of symptoms and symptom severity. Areas covered: In this review, the author discusses animal models of ASD used as targets for drug discovery, focusing primarily on non-syndromic models, primarily rodents...
October 3, 2017: Expert Opinion on Drug Discovery
Antonio Gómez-Outes, Minerva García-Fuentes, Mª Luisa Suárez-Gea
In the last decade, several direct oral anticoagulants (DOAC) targeting thrombin (dabigatran) or activated factor X (FXa) (rivaroxaban, apixaban and edoxaban) have been marketed for a number of indications related to prophylaxis and treatment of thrombotic diseases. All these drugs are effective in preventing thrombosis, but are associated with an increased bleeding risk. Areas covered: This review includes a summary of new targets for anticoagulation (e.g.: FXIa, FXIIa, protein disulfide isomerase, polyphosphates, etc...
September 27, 2017: Expert Opinion on Drug Discovery
Elizabeth C M de Lange, Willem van den Brink, Yumi Yamamoto, Wilhelmus E A de Witte, Yin Cheong Wong
CNS drug development has been hampered by inadequate consideration of CNS pharmacokinetic (PK), pharmacodynamics (PD) and disease complexity (reductionist approach). Improvement is required via integrative model-based approaches. Areas covered: The authors summarize factors that have played a role in the high attrition rate of CNS compounds. Recent advances in CNS research and drug discovery are presented, especially with regard to assessment of relevant neuro-PK parameters. Suggestions for further improvements are also discussed...
September 21, 2017: Expert Opinion on Drug Discovery
Hongbo Guo, Hui Peng, Andrew Emili
To ​​​​understand and manipulate biochemical processes and signaling pathways, the knowledge of endogenous protein-metabolite interactions would be extremely helpful. Recent developments in precision mass spectrometry, high-throughput proteomics and sensitive metabolomic profiling are beginning to converge on a possible solution, heralding a new era of global metabolome-proteome 'interactome' studies that promise to change biomedical research and drug discovery. Areas covered: Here, we review innovative mass spectrometry-based methods and recent pioneering studies aimed at elucidating the physical associations of small molecule ligands with cellular proteins...
September 21, 2017: Expert Opinion on Drug Discovery
Teruo Murakami
In pharmacotherapy, drugs are mostly taken orally to be absorbed systemically from the small intestine, and some drugs are known to have preferential absorption sites in the small intestine. It would therefore be valuable to know the absorption sites of orally administered drugs and the influencing factors. Areas covered:In this review, the author summarizes the reported absorption sites of orally administered drugs, as well as, influencing factors and experimental techniques. Information on the main absorption sites and influencing factors can help to develop ideal drug delivery systems and more effective pharmacotherapies...
September 17, 2017: Expert Opinion on Drug Discovery
Lidia Bravo, Juan Antonio Mico, Esther Berrocoso
Tramadol is an opioid drug that, unlike classic opioids, also modulates the monoaminergic system by inhibiting noradrenergic and serotoninergic reuptake. For this reason, tramadol is considered an atypical opioid. These special pharmacological characteristics have made tramadol one of the most commonly prescribed analgesic drugs to treat moderate to severe pain. Areas covered: The aim of this review is to provide a historical description of the biochemistry, pharmacokinetics and particularly, the mechanisms of action of tramadol...
September 17, 2017: Expert Opinion on Drug Discovery
(no author information available yet)
No abstract text is available yet for this article.
September 13, 2017: Expert Opinion on Drug Discovery
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