Skip Ribbon Commands
Skip to main content
Translate
Translate this website into the following languages:



Close Tab
Donations
<a href="/"><img alt="UC San Diego Health"  oncontextmenu="return false;" style="position:relative;top:10px" src="data:image/png;base64,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" /></a>
menu iconMenu
search iconSearch

Finding Molecular Targets of an HIV Drug used in Cancer Therapy

 

April 28, 2011  |  

Use of chemical systems biology may represent the future of drug discovery

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.”

# # #

Media Contact: Debra Kain, 619-543-6163, ddkain@ucsd.edu


Related Specialties

Cancer
AIDS/HIV+


Media Contact

Share This Article


Related News

5/2/2016
Local philanthropists Gary and Mary West have provided $11.8 million to the University of California San Diego to create a state-of-the-art senior emergency care unit to be housed within the Emergency ...
4/27/2016
Urologists at University of California San Diego School of Medicine and Genesis Healthcare Partners have tested a new model of care for patients with low-risk prostate cancer. The evidence-based appro ...
4/26/2016
The California HIV/AIDS Research Program (CHRP) of University of California has awarded grants totaling $9.4 million to three teams of investigators to provide and evaluate PrEP – the HIV prevention p ...
4/26/2016
While technological advances have made it easier to map our microbiomes and metabolomes, these studies typically take too long for that data to be medically useful. Researchers at the University of Ca ...



Follow Us