New approaches to drug discovery and development: a mechanism-based approach to pharmaceutical research and its application to BNP7787, a novel chemoprotective agent

2003 ◽  
Vol 52 (0) ◽  
pp. 3-15 ◽  
Author(s):  
Frederick H. Hausheer ◽  
Harry Kochat ◽  
Aulma R. Parker ◽  
Daoyuan Ding ◽  
Shije Yao ◽  
...  
2021 ◽  
Vol 23 (4) ◽  
Author(s):  
Nadia Terranova ◽  
Karthik Venkatakrishnan ◽  
Lisa J. Benincosa

AbstractThe exponential increase in our ability to harness multi-dimensional biological and clinical data from experimental to real-world settings has transformed pharmaceutical research and development in recent years, with increasing applications of artificial intelligence (AI) and machine learning (ML). Patient-centered iterative forward and reverse translation is at the heart of precision medicine discovery and development across the continuum from target validation to optimization of pharmacotherapy. Integration of advanced analytics into the practice of Translational Medicine is now a fundamental enabler to fully exploit information contained in diverse sources of big data sets such as “omics” data, as illustrated by deep characterizations of the genome, transcriptome, proteome, metabolome, microbiome, and exposome. In this commentary, we provide an overview of ML applications in drug discovery and development, aligned with the three strategic pillars of Translational Medicine (target, patient, dose) and offer perspectives on their potential to transform the science and practice of the discipline. Opportunities for integrating ML approaches into the discipline of Pharmacometrics are discussed and will revolutionize the practice of model-informed drug discovery and development. Finally, we posit that joint efforts of Clinical Pharmacology, Bioinformatics, and Biomarker Technology experts are vital in cross-functional team settings to realize the promise of AI/ML-enabled Translational and Precision Medicine.


Author(s):  
Shuxing Zhang

Machine learning techniques have been widely used in drug discovery and development, particularly in the areas of cheminformatics, bioinformatics and other types of pharmaceutical research. It has been demonstrated they are suitable for large high dimensional data, and the models built with these methods can be used for robust external predictions. However, various problems and challenges still exist, and new approaches are in great need. In this Chapter, the authors will review the current development of machine learning techniques, and especially focus on several machine learning techniques they developed as well as their application to model building, lead discovery via virtual screening, integration with molecular docking, and prediction of off-target properties. The authors will suggest some potential different avenues to unify different disciplines, such as cheminformatics, bioinformatics and systems biology, for the purpose of developing integrated in silico drug discovery and development approaches.


2012 ◽  
Vol 107 (7) ◽  
pp. 831-845 ◽  
Author(s):  
Anna Caroline C Aguiar ◽  
Eliana MM da Rocha ◽  
Nicolli B de Souza ◽  
Tanos CC França ◽  
Antoniana U Krettli

2007 ◽  
Vol 4 (3) ◽  
pp. 294-301
Author(s):  
Neeraj Upmanyu ◽  
Gopal Garg ◽  
Archana Dolly ◽  
Pradeep Mishra

Ever since Nuclear Magnetic Resonance (NMR) spectroscopy hit the analytical scene; its capabilities and applications continue to evolve. Originally designed as a way to verify the structure of relatively small compounds, the technology of NMR has exploded and become a valuable means for studying protein structure. NMR has proved to be a valuable tool in pharmaceutical research, as it has entered new arena of drug discovery and structural genomics. NMR can provide information on the three-dimensional structures of small molecules in solution, high-molecular-weight complexes, and the details of enzyme mechanisms that can be used to aid in drug design. In the present scenario, the availability of high magnetic fields; improved software, high resolution probes, and electronics; more versatile pulse programmers; and most importantly the development of 2D, 3D and 4D NMR, have revolutionized the field of drug discovery and development.


2012 ◽  
pp. 1460-1482
Author(s):  
Shuxing Zhang

Machine learning techniques have been widely used in drug discovery and development, particularly in the areas of cheminformatics, bioinformatics and other types of pharmaceutical research. It has been demonstrated they are suitable for large high dimensional data, and the models built with these methods can be used for robust external predictions. However, various problems and challenges still exist, and new approaches are in great need. In this Chapter, the authors will review the current development of machine learning techniques, and especially focus on several machine learning techniques they developed as well as their application to model building, lead discovery via virtual screening, integration with molecular docking, and prediction of off-target properties. The authors will suggest some potential different avenues to unify different disciplines, such as cheminformatics, bioinformatics and systems biology, for the purpose of developing integrated in silico drug discovery and development approaches.


2016 ◽  
Vol 12 ◽  
pp. 2694-2718 ◽  
Author(s):  
Sumudu P Leelananda ◽  
Steffen Lindert

The process for drug discovery and development is challenging, time consuming and expensive. Computer-aided drug discovery (CADD) tools can act as a virtual shortcut, assisting in the expedition of this long process and potentially reducing the cost of research and development. Today CADD has become an effective and indispensable tool in therapeutic development. The human genome project has made available a substantial amount of sequence data that can be used in various drug discovery projects. Additionally, increasing knowledge of biological structures, as well as increasing computer power have made it possible to use computational methods effectively in various phases of the drug discovery and development pipeline. The importance of in silico tools is greater than ever before and has advanced pharmaceutical research. Here we present an overview of computational methods used in different facets of drug discovery and highlight some of the recent successes. In this review, both structure-based and ligand-based drug discovery methods are discussed. Advances in virtual high-throughput screening, protein structure prediction methods, protein–ligand docking, pharmacophore modeling and QSAR techniques are reviewed.


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