Navigation Links
Finding molecular targets of an HIV drug used in cancer therapy
Date:4/28/2011

Researchers at the University of California, San Diego and Hunter College of the City University of New York (CUNY) have identified potential human molecular targets of the anti-HIV drug Nelfinavir, which may explain why the drug is also effective as a cancer therapy. Their study will be published in the online edition of PLoS Computational Biology on April 28.

Nelfinivir is a protease inhibitor that prevents replication of the HIV virus, but it has also been found to have a positive effect on a number of solid tumor types, and is currently in clinical trial as a cancer therapy. However, the mechanism of how the drug worked in humans was not clear.

The researchers discovered that Nelfinavir may interact with multiple human protein kinases enzymes that modify other proteins and regulate the majority of cellular pathways. Protein kinases comprise approximately 2 percent of the human genome, and are important anti-cancer drug targets.

Surprisingly, the interactions between Nelfinavir and kinases are much weaker than those from more specific, rationally designed drugs, said Philip Bourne, PhD, professor of pharmacology at UC San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences. Bourne and colleagues suggest that it is the collective effect of these weak interactions that leads to the clinical efficacy of Nelfinavir.

The research team Li Xie, PhD, from UC San Diego, Thomas Evangelidis, a former graduate student in Bourne's lab, now at the University of Manchester, and research scientist Lei Xie, PhD, now an associate professor at Hunter College, CUNY combined a wide array of computational techniques to investigate the molecular mechanisms underlying Nelfinavir's observed anti-cancer effect.

While drug molecules are designed to bind to targeted proteins in order to achieve a therapeutic effect, small drug molecules can attach to off-target proteins with similar binding sites. The result may be unwanted side effects or, as in the case of Nelfinavir, a secondary and positive effect.

In the traditional strategy for drug discovery, scientists use high-throughput screening to find a suitable drug target. However, utilizing the RCSB Protein Data Bank a worldwide repository of tens of thousands of three-dimensional protein structures the UCSD researchers computationally compared binding sites in order to identify which proteins might be unintended targets.

Taking a single drug molecule, they looked at all proteins encoded by the human proteome to which that molecule could possibly bind.

"Computer analysis allows us to search for other binding sites that match a particular drug-binding site like looking for other locks that can be opened by the same key," said Lei Xie.

While this novel computational pipeline is promising in fishing for drug targets from a significant portion of the human genome, Lei Xie cautioned that "it is especially challenging to validate weak drug-target interactions both computationally and experimentally." He added that modeling such drug actions requires that scientists find relevant proteins and then examine them in the context of a biological network, while at the same time simulating their cumulative effects.

"This is indeed challenging, but uncovering which protein receptors Nelfinavir binds to may help us design better anti-cancer drugs," said Bourne. "It is hard not to believe that this broad-based systems approach represents the future of drug discovery, at least as far as small-molecule drugs are concerned."


'/>"/>

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

Related medicine news :

1. OHSU expert co-authors study finding treatment for rare lung disease
2. Ovarian cancer finding may be a win-win for at-risk women who wish to have a family
3. Researchers present new findings on cancer and gene therapy
4. UPCI, Pitt researchers present findings of cancer studies at AACR 102nd Annual Meeting
5. Surprising finding from smoke inhalation study
6. Finding of long-sought drug target structure may expedite drug discovery
7. New findings on drug tolerance in TB suggest ideas for shorter cures
8. Latest findings of Dartmouth HIV/AIDS study could turn treatment on its head
9. Research provides new findings on drug delivery with nanoparticles
10. SMFM highlights significance of spina bifida research findings
11. Most Guidelines for Infectious Diseases Dont Come From Clinical Trial Findings
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:9/20/2017)... ... September 20, 2017 , ... Health & Safety Institute (HSI) is offering discounted ... and 40-Hour courses from now until November 30, 2017 to assist with the clean-up ... prices to all businesses and government agencies – whether or not they will be ...
(Date:9/20/2017)... ... September 20, 2017 , ... “Finn Mouseson”: follows the exciting story ... average life. This mouse sets out on a journey that will show that friends ... the creation of newly published author and illustrator, Melody Gersonde-Mickelson, who has earned a ...
(Date:9/20/2017)... ... September 20, 2017 , ... “The Foggy Road to Moorwick”: the adventures of a young ... creation of published author, Jeanine Liston, a busy mother of five who used her time ... been writing this book for over twenty years. It was a way to give ...
(Date:9/19/2017)... ... September 19, 2017 , ... ... Brazilian jiu-jitsu community have raised more than $15,000 in just a couple of ... professional submission grappling matches and world-class instructor seminars, organizers expect to double those ...
(Date:9/19/2017)... ... ... Trusted debt-reduction firm CreditAssociates, LLC has announced two important milestones. To date, ... million in resolved debt for its clients. , Credit card debt, unpaid hospital bills, ... debt settled by the company. With more than a decade of combined service to ...
Breaking Medicine News(10 mins):
(Date:9/6/2017)... N.Y. , Sept. 6, 2017   PDI , ... announced it will host an educational session focused on ... bloodstream infection (CLABSI) prevention at the 2017 Annual Scientific ... which will take place at the Phoenix ... from Sept. 16-19, will also feature PDI,s ...
(Date:9/5/2017)... N.J. , Sept. 5, 2017  Getinge, ... has created a vibrant charitable donation program -- ... and support congenital heart defect research by The ... providers and the general public are encouraged to ... and submit the completed artwork to the gallery ...
(Date:9/1/2017)... 1, 2017  Bayer will present the latest research from ... Medical Oncology (ESMO) 2017 Congress, September 8-12 in ... preclinical and clinical data on Bayer,s marketed portfolio and late-stage ... "We value the ... cancer research at ESMO," said Carsten Brunn , Head ...
Breaking Medicine Technology: