Navigation Links
New computational technique can predict drug side effects
Date:12/11/2007

Early identification of adverse effects of drugs before they are tested in humans is crucial in developing new therapeutics, as unexpected effects account for a third of all drug failures during the development process. Now researchers at the University of California, San Diego (UCSD) have developed a novel technique using computer modeling to identify potential side effects of pharmaceuticals, and have used the technique to study a class of drugs that includes tamoxifen, the most prescribed drug in the treatment of breast cancer. Their study is currently available on line at PLoS Computational Biology.

Conventional test methods screen compounds in animal studies in advance of human trials in the hope of identifying the side effects of promising therapeutics. The UCSD team led by Philip Bourne, Ph.D., professor of pharmacology at UCSDs Skaggs School of Pharmacy and Pharmaceutical Sciences and Lei Xie, Ph.D., of the San Diego Supercomputer Center at UCSD instead uses the power of computational modeling to screen specific drug molecules using a worldwide repository, the Protein Data Bank (PDB), containing tens of thousands of three-dimensional protein structures.

Drug molecules are designed to bind to targeted proteins in order to achieve a therapeutic affect, but if the small drug molecule that functions as a key attaches to an off-target protein that has a similar binding site, or lock, side effects can result.

To identify which proteins might be unintended targets, the UCSD researchers take a single drug molecule and look for how it might bind to as many of the proteins encoded by the human proteome as possible. In this published case study, they looked at Select Estrogen Receptor Modulators (SERMs), a class of drug that includes tamoxifen, to illustrate the novel approach.

The computer procedure we developed starts with an existing three-dimensional model of a pharmaceutical, showing the structure of a drug molecule bound to its target protein; in this case, the SERM bound to the estrogen receptor, said Bourne, who is co-director of the PDB. The scientists then use computer analysis to search for other binding sites that match that drug binding site like looking for other locks that can be opened by the same key.

In this study, the team found a previously unidentified protein target for SERMs. The identification of this secondary binding site explains known adverse effects, and opens the door to modifying the drug in a way that maintains binding to the intended target, but reduces binding to the second site.

If a drug has adverse side effects, it is likely that drug is also binding to an unintended, secondary molecule; in other words, the key that allows it to attach to its target fits more than one lock, said Bourne. He explained that using this computational technique to find another lock could result in one of three things: the new lock might show no effect; the lock could explain an adverse side effect of the drug; or the research could potentially discover a new therapeutic effect for an existing drug drug repositioning.

The UCSD researchers are continuing their studies, which Bourne says can be applied to any drug on the market for which a structure of the drug bound to the receptor exists in the PDB. Bourne emphasized that results from this approach still needed to be tested experimentally.


'/>"/>

Contact: Debra Kain
ddkain@ucsd.edu
619-543-6163
University of California - San Diego
Source:Eurekalert

Related medicine news :

1. Carnegie Mellon Establishes Ray and Stephanie Lane Center for Computational Biology
2. A new computational technique predicts side-effects of a major cancer drug
3. Eye-staining technique offers early detection for dry eye syndrome
4. New technique detects specific chromosomal damage, may indicate lung cancer risk
5. The Pharma & Life Sciences Best Practice Database: an Industry Resource for Successful Techniques and Performance Benchmarks for Reaching the Top
6. Latest DES Analysis Stresses Importance of Physicians Well-Trained in Implantation Technique and Patient Follow-Up
7. Accuray Receives FDA Clearance for New Dose Calculation Technique for Body Radiosurgery
8. Radiation therapy technique reduces length of prostate cancer treatment
9. Radiation therapy technique reduces length of prostate cancer treatment
10. IVF technique enables pregnancy without multiple births, Stanford researchers find
11. UT Southwestern investigating hypothermic technique in treating pediatric head injuries
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/23/2017)... , ... March 23, 2017 , ... ... audit software solution, iCode Assurance, at HCCA’s 21st annual Compliance Institute on March ... the coding audit process for all medical chart types with a comprehensive set ...
(Date:3/23/2017)... ... , ... “Wounded Woman Be Ye Healed-Passing On A Legacy”: a call to ... the creation of published author, Desiree M Webb, a registered nurse, minister of music, ... happily married to her husband, Paul, for over twenty-nine years. Desiree enjoys writing, ...
(Date:3/23/2017)... ... March 23, 2017 , ... “A Respectful Response To Atheist ... To Atheist Manifesto” is the creation of published author Richard Hostetter, a former ... years. He holds graduate degrees from Kent State University and the University of ...
(Date:3/23/2017)... (PRWEB) , ... March 23, 2017 , ... ... today announced the publication of “Profiling protein expression in circulating tumor cells using ... publication describes the use of the Vortex technology to capture CTCs ...
(Date:3/22/2017)... ... 2017 , ... Catalent Pharma Solutions, the leading global provider ... products, today announced that it had won the ‘Clinical Supply Chain Excellence’ category ... International Exhibition & Convention Centre, Singapore. The award was presented at the conference ...
Breaking Medicine News(10 mins):
(Date:3/22/2017)... Inc. today announced the appointment of Martyn Coombs as ... of ImaginAb, said "At ImaginAb we have exciting science and technology. ... our business, particularly in commercializing and making step changes in the ... realize our potential." ... Mr. Coombs is a recognized industry leader in nuclear medicine and ...
(Date:3/22/2017)... N.J. , March 22, 2017  CANTEL MEDICAL CORP. ... B. Hansen , President and CEO, will be presenting at ... at the Westin Grand Central Hotel in New ... April 5, 2017 at 3:00 p.m. ET. In addition, management ... A live audio webcast will be available ...
(Date:3/22/2017)... 22, 2017 Research and Markets has ... Inhibitors Market & Clinical Pipeline Insight 2022" drug pipelines ... ... Clinical Pipeline Insight 2022 report gives comprehensive insight on clinical ... immune check point inhibitors as main streamline drugs in the ...
Breaking Medicine Technology: