Science Current Events | Science News |

Automated design for drug discovery

December 13, 2012
A system of 'automated design' for new drugs could help develop the complex therapies needed for many medical conditions while also improving drug safety and efficiency, new research from the University of Dundee has shown.

The 'Moneyball' approach taken by the research team utilises the principles of advanced statistical and data analysis which have seen to be increasingly influential in areas as varied as sport, finance and in forecasting the recent US Presidential election.

As more complex drugs are needed to treat more complicated problems - particularly in areas such as neuroscience, infectious diseases and cancer - the task facing biologists and chemists is daunting. However, researchers at the College of Life Sciences at Dundee, in collaboration with partners in North America, have shown that an automated computational process analysing huge amounts of existing data could provide a valuable new tool in drug discovery.

The innovative approach taken by the research team mimics the creative process of human chemists, where drug molecules are steadily improved through successive cycles of design and selection.

"One of the things that makes drug discovery so hard is that you're trying to improve several different properties at the same time," said Professor Andrew Hopkins, Chair of Medicinal Informatics at Dundee. "Evolution is a mechanism than can be applied to solving these kinds of optimisation problems, and the iterative process of adaption and selection of hundreds of thousand of possible solutions can be simulated in a computer.

"We have effectively proved the concept of automated design of new compounds, showing that by using algorithms to process massive amounts of data we can tackle problems of huge complexity. The system solves the design problem by using computational evolution to mimic the design process of human chemists but running it on a very large scale."

The research is published in the journal Nature. The research team's work is funded by the Biotechnology and Biological Sciences Research Council.

Drugs have to be able to deliver their primary effects and not present adverse side effects or toxicity that render them unsafe. But for complex conditions drugs also have to be designed to hit multiple targets. Designing drugs to this kind of multi-target profile is a complex and exceedingly difficult task for medicinal chemistry.

Professor Hopkins and colleagues developed an automated adaptive design approach that can mimic the creative, iterative process of medicinal chemists by using computational evolution of large numbers of compounds. They initially used it to look at an existing drug, Donepezil, which is used in treating Alzheimer's Disease.

"Professor Sir James Black, the Nobel Laureate and former Chancellor of the University, proposed that 'the most fruitful basis for the discovery of a new drug is to start with an old drug' and we followed that advice," said Professor Hopkins.

"We took the structure of Donepezil as a starting point and from there the system evolved its structure, computationally, over many generations to a variety of different profiles across a range of drug targets. The predicted profiles were then tested experimentally and we found that 75% of them were confirmed to be correct.

"This proof of concept shows that we could make significant advances in discovering and designing complex drugs, which could lead to improvements in safety and efficacy, while also potentially reducing the cost of drug discovery, which is a high-risk and expensive process."

Professor Hopkins said improvements in data capture and management were key to developing the research.

"Just a few years ago this would not have been possible because we need the existing drug data to build on and it was not held in a way that it could be analysed like this. But there have been significant developments, aided by groups like ChEMBL in Cambridge, who are funded by The Wellcome Trust, in making drug design data available in a format computers can process. What we have found particularly exciting is the way the algorithm has been able to learn from the human experience of drug design and mimic it on a massive scale to solve complex design problems."

This phenomenon is reflected in the name of a new spin out company which has been formed to commercialise the technology - ex scientia - which is the Latin for "from knowledge".

University of Dundee

Related Drug Discovery Current Events and Drug Discovery News Articles

BU researchers discover that Klotho is neuroprotective against Alzheimer's disease
Boston University School of Medicine researchers may have found a way to delay or even prevent Alzheimer's disease (AD).

Anti-pain agent shrinks oral cancers, leaves healthy tissues alone
Mouse models of human oral cancer treated with an agent called capsazepine showed dramatic tumor shrinkage without damage to surrounding tissues, researchers from the School of Dentistry and School of Medicine at The University of Texas Health Science Center at San Antonio found.

Potential new flu drugs target immune response, not virus
The seriousness of disease often results from the strength of immune response, rather than with the virus, itself.

Drug's effect on Alzheimer's may depend on severity of disease
A cancer drug that has shown promise against Alzheimer's disease in mice and has begun early clinical trials has yielded perplexing results in a novel mouse model of AD that mimics the genetics and pathology of the human disease more closely than any other animal model.

Innovative Technique May Transform the Hunt for New Antibiotics and Cancer Therapies
Antibiotic resistance is depleting our arsenal against deadly diseases and infections, such as tuberculosis and Staph infections, but recent research shows promise to speed up the drug discovery process.

UGA researchers use nanoparticles to enhance chemotherapy
University of Georgia researchers have developed a new formulation of cisplatin, a common chemotherapy drug, that significantly increases the drug's ability to target and destroy cancerous cells.

Potential Alzheimer's drug prevents abnormal blood clots in the brain
Without a steady supply of blood, neurons can't work. That's why one of the culprits behind Alzheimer's disease is believed to be the persistent blood clots that often form in the brains of Alzheimer's patients, contributing to the condition's hallmark memory loss, confusion and cognitive decline.

New transdermal SARM drug for muscle-wasting offers hope for older cancer patients
Muscle wasting that occurs as a result of cancer negatively impacts the well-being and recovery prospects of millions of patients, particularly the rapidly-growing elderly populations in Western societies.

Stanford bioengineers invent a way to speed up drug discovery
Think of the human body as an intricate machine whose working parts are proteins: molecules that change shape to enable our organs and tissues to perform tasks such as breathing or eating or thinking.

How a new approach to funding Alzheimer's research could pay off
More than 5 million Americans suffer from Alzheimer's disease, the affliction that erodes memory and other mental capacities, but no drugs targeting the disease have been approved by the U.S. Food and Drug Administration since 2003.
More Drug Discovery Current Events and Drug Discovery News Articles

Drug Discovery and Development: Technology in Transition, 2e

Drug Discovery and Development: Technology in Transition, 2e
by Raymond G Hill (Author)

The modern pharmacopeia has enormous power to alleviate disease, and owes its existence almost entirely to the work of the pharmaceutical industry. This book provides an introduction to the way the industry goes about the discovery and development of new drugs. The first part gives a brief historical account from its origins in the mediaeval apothecaries' trade, and discusses the changing understanding of what we mean by disease, and what therapy aims to achieve, as well as summarising case histories of the discovery and development of some important drugs. The second part focuses on the science and technology involved in the discovery process: the stages by which a promising new chemical entity is identified, from the starting point of a medical need and an idea for addressing it. A...

Drug Discovery: Practices, Processes, and Perspectives

Drug Discovery: Practices, Processes, and Perspectives
by Jie Jack Li (Editor), E. J. Corey (Editor)

Sets forth the history, state of the science, and future directions of drug discoveryEdited by Jie Jack Li and Nobel laureate E. J. Corey, two leading pioneers in drug discovery and medicinal chemistry, this book synthesizes great moments in history, the current state of the science, and future directions of drug discovery into one expertly written and organized work. Exploring all major therapeutic areas, the book introduces readers to all facets and phases of drug discovery, including target selection, biological testing, drug metabolism, and computer-assisted drug design.Drug Discovery features chapters written by an international team of pharmaceutical and medicinal chemists. Contributions are based on a thorough review of the current literature as well as the authors' firsthand...

Drugs: From Discovery to Approval

Drugs: From Discovery to Approval
by Rick Ng (Author)

"Concise and easy to read, the book quickly introduces basic concepts, then moves on to discuss target selection and the drug discovery process for both small and large molecular drugs."
—Doody's Reviews, May 2009"The second edition of a book that offers a user-friendly step-by-step introduction to all the key processes involved in bringing a drug to the market, including the performance of preclinical trials."
—Chemistry World, February 2009The new edition of this best-selling book continues to offer a user-friendly, step-by-step introduction to all the key processes involved in bringing a drug to the market, including the performance of pre-clinical studies, the conduct of human clinical trials, regulatory controls, and even the manufacturing processes for pharmaceutical...

The Evolution of Drug Discovery

The Evolution of Drug Discovery
by Enrique Ravina (Author), Hugo Kubinyi (Foreword)

The discovery and use of medicines is just as fascinating a human scientific endeavor as space flight or the tracing of human evolution. It is also the everyday task of hundreds of thousands of pharmacists, pharmaceutical chemists and researchers worldwide.
Based on his profound knowledge of past and present paradigms in the development of medicines, Enrique Ravina takes the reader from the very beginnings of pharmacology to the multibillion-dollar business it represents today. Recounting the often spectacular successes and failures of innovative drugs as well as the people who discovered them, he brings abstract science to life in anecdotal form.
For anyone with a more than superficial interest in the science of drugs and all those interested in knowing how drugs have been...

The Future of Drug Discovery: Who Decides Which Diseases to Treat?

The Future of Drug Discovery: Who Decides Which Diseases to Treat?
by Tamas Bartfai (Author), Graham V. Lees (Author)

The Future of Drug Discovery: Who decides which diseases to treat? provides a timely and detailed look at the efforts of the pharmaceutical industry and how they relate, or should relate, to societal needs. The authors posit that as a result of increasing risk aversion and accelerated savings in research and development, the industry is not developing drugs for increasingly prevalent diseases, such as Alzheimer's disease, untreatable pain, antibiotics and more. This book carefully exposes the gap between the medicines and therapies we need and the current business path. By analyzing the situation and discussing prospects for the next decade, the The Future of Drug Discovery is a timely book for all those who care about the development needs for drugs for disease.This thought-provoking...

Real World Drug Discovery: A Chemist's Guide to Biotech and Pharmaceutical Research

Real World Drug Discovery: A Chemist's Guide to Biotech and Pharmaceutical Research
by Robert M. Rydzewski (Author)

Drug discovery increasingly requires a common understanding by researchers of the many and diverse factors that go into the making of new medicines. The scientist entering the field will immediately face important issues for which his education may not have prepared him: project teams, patent law, consultants, target product profiles, industry trends, Gantt charts, target validation, pharmacokinetics, proteomics, phenotype assays, biomarkers, and many other unfamiliar topics for which a basic understanding must somehow be obtained. Even the more experienced scientist can find it frustratingly difficult to get an overview of the many factors involved in modern drug discovery and often only after years of exploring does a whole and integrated picture emerge in the mind of the researcher....

Drug Discovery: A History

Drug Discovery: A History
by Walter Sneader (Author)

Written by a leading authority with an excellent reputation and ability for writing a good narrative, Drug Discovery: A History is a far cry from simply a list of chemical structures.This lively new text considers the origins, development and history of medicines that generate high media interest and have a huge social and economic impact on society.Set within a wide historical, social and cultural context, it provides expanded coverage of pre-twentieth century drugs, the huge advances made in the twentieth century and the latest developments in drug research.Hallmark features:Up-to-the-minute information in drug researchVignettes of special and unusual information, and anecdotesDiscusses drug prototypes from all sourcesMore comprehensive than other volumes on history of drug...

Hallelujah Moments: Tales of Drug Discovery

Hallelujah Moments: Tales of Drug Discovery
by Eugene H. Cordes (Author)

Drug discovery in the pharmaceutical industry has important consequences for the health and wellbeing of people everywhere. However, the general public knows little about the paths through which basic research findings are translated into products that protect or restore human health: the route from the laboratory bench to the bedside. In Hallelujah Moments, Eugene Cordes reveals how some of the most important and influential drugs have been brought into the practice of clinical medicine through the wit and determination of scientists in academia and industry. He shares his firsthand knowledge of the drug-discovery world, having spent a long and distinguished career in both the academic and industrial settings. These tales are "adventure stories," and they trace the route of important...

Collaborative Innovation in Drug Discovery: Strategies for Public and Private Partnerships (Wiley Series on Technologies for the Pharmaceutical Industry)

Collaborative Innovation in Drug Discovery: Strategies for Public and Private Partnerships (Wiley Series on Technologies for the Pharmaceutical Industry)
by Rathnam Chaguturu (Editor), Ferid Murad (Editor)

Can academia save the pharmaceutical industry?The pharmaceutical industry is at a crossroads. The urgent need for novel therapies cannot stem the skyrocketing costs and plummeting productivity plaguing R&D, and many key products are facing patent expiration. Dr. Rathnam Chaguturu presents a case for collaboration between the pharmaceutical industry and academia that could reverse the industry's decline. Collaborative Innovation in Drug Discovery: Strategies for Public and Private Partnerships provides insight into the potential synergy of basing R&D in academia while leaving drug companies to turn hits into marketable products. As Founder and CEO of iDDPartners, focused on pharmaceutical innovation, Founding president of the International Chemical Biology Society, and Senior...

Molecular Pharmacology: From DNA to Drug Discovery

Molecular Pharmacology: From DNA to Drug Discovery
by John Dickenson (Author), Fiona Freeman (Author), Chris Lloyd Mills (Author), Christian Thode (Author), Shiva Sivasubramaniam (Author)

This textbook provides a fresh, comprehensive and accessible introduction to the rapidly expanding field of molecular pharmacology. Adopting a drug target-based, rather than the traditional organ/system based, approach this innovative guide reflects the current advances and research trend towards molecular based drug design, derived from a detailed understanding of chemical responses in the body. Drugs are then tailored to fit a treatment profile, rather than the traditional method of ‘trial and error’ drug discovery which focuses on testing chemicals on animals or cell cultures and matching their effects to treatments. Providing an invaluable resource for advanced under-graduate and MSc/PhD students, new researchers to the field and practitioners for continuing professional...

© 2014