Featured Research

from universities, journals, and other organizations

Finding molecular targets of an HIV drug used in cancer therapy

Date:
April 30, 2011
Source:
University of California - San Diego
Summary:
Researchers 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.

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."


Story Source:

The above story is based on materials provided by University of California - San Diego. The original article was written by Debra Kain. Note: Materials may be edited for content and length.


Journal Reference:

  1. Li Xie, Thomas Evangelidis, Lei Xie, Philip E. Bourne. Drug Discovery Using Chemical Systems Biology: Weak Inhibition of Multiple Kinases May Contribute to the Anti-Cancer Effect of Nelfinavir. PLoS Computational Biology, 2011; 7 (4): e1002037 DOI: 10.1371/journal.pcbi.1002037

Cite This Page:

University of California - San Diego. "Finding molecular targets of an HIV drug used in cancer therapy." ScienceDaily. ScienceDaily, 30 April 2011. <www.sciencedaily.com/releases/2011/04/110428201112.htm>.
University of California - San Diego. (2011, April 30). Finding molecular targets of an HIV drug used in cancer therapy. ScienceDaily. Retrieved July 31, 2014 from www.sciencedaily.com/releases/2011/04/110428201112.htm
University of California - San Diego. "Finding molecular targets of an HIV drug used in cancer therapy." ScienceDaily. www.sciencedaily.com/releases/2011/04/110428201112.htm (accessed July 31, 2014).

Share This




More Health & Medicine News

Thursday, July 31, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

House Republicans Vote to Sue Obama Over Healthcare Law

House Republicans Vote to Sue Obama Over Healthcare Law

Reuters - US Online Video (July 31, 2014) The Republican-led House of Representatives votes to sue President Obama, accusing him of overstepping his executive authority in making changes to the Affordable Care Act. Mana Rabiee reports. Video provided by Reuters
Powered by NewsLook.com
Despite Health Questions, E-Cigs Are Beneficial: Study

Despite Health Questions, E-Cigs Are Beneficial: Study

Newsy (July 31, 2014) Citing 81 previous studies, new research out of London suggests the benefits of smoking e-cigarettes instead of regular ones outweighs the risks. Video provided by Newsy
Powered by NewsLook.com
Dangerous Bacteria Kills One in Florida

Dangerous Bacteria Kills One in Florida

AP (July 31, 2014) Sarasota County, Florida health officials have issued a warning against eating raw oysters and exposing open wounds to coastal and inland waters after a dangerous bacteria killed one person and made another sick. (July 31) Video provided by AP
Powered by NewsLook.com
Health Insurers' Profits Slide

Health Insurers' Profits Slide

Reuters - Business Video Online (July 30, 2014) Obamacare-related costs were said to be behind the profit plunge at Wellpoint and Humana, but Wellpoint sees the new exchanges boosting its earnings for the full year. Fred Katayama reports. Video provided by Reuters
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



    Save/Print:
    Share:

    Free Subscriptions


    Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

    Get Social & Mobile


    Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

    Have Feedback?


    Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
    Mobile: iPhone Android Web
    Follow: Facebook Twitter Google+
    Subscribe: RSS Feeds Email Newsletters
    Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins