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:4/30/2016)... ... April 30, 2016 , ... Saturday, April 30, marks ... impact on public health. The World Veterinary Association (WVA) and the World Organization ... selected continuing education with a One Health focus, which emphasizes how veterinarians pursue ...
(Date:4/30/2016)... ... ... all of us, but there are things we can do to improve the odds of staying ... and more that there are simple, yet important steps that can be taken to maintain good ... recommends for her patients include;, , exercise , healthy ...
(Date:4/29/2016)... ... April 30, 2016 , ... Mercy College is expanding its Graduate Business Programs ... be expanding due to high demand: Master of Business Administration (MBA), Master of Organizational ... , School of Business Graduate Program Chair Dr. Ray Manganelli said: “We ...
(Date:4/29/2016)... , ... April 29, 2016 , ... ... by the Accreditation Council for Graduate Medical Education (ACGME) that it has received ... is the first accreditation of three residency programs that Memorial is currently pursuing, ...
(Date:4/29/2016)... ... April 29, 2016 , ... On Tuesday, April 26, ... the Southeast, celebrated the signature of Gov. Nathan Deal on SB 258, the “Rural ... (R - Cumming), offers a 70% tax credit to individuals and corporations which donate ...
Breaking Medicine News(10 mins):
(Date:4/27/2016)... , April 27, 2016  Bayer Animal Health ... senior from the University of Florida College of ... Bayer Excellence in Communication Award (BECA). Brittany was ... were awarded a total of $70,000 in scholarship ... four years, Bayer has provided a total of ...
(Date:4/27/2016)... SAN FRANCISCO , April 27, 2016 /PRNewswire/ ... to reach over USD 2.14 billion by 2022, ... Research, Inc.       (Logo: http://photos.prnewswire.com/prnh/20150105/723757 ... key technological advancement affecting the efficiency and accuracy ... hence, the persistent demand for novel urinalysis instruments ...
(Date:4/26/2016)... Hill-Rom Holdings, Inc. (NYSE: HRC ) ... Deutsche Bank 41 st Annual Health Care Conference on ... You are invited to listen to the live discussion via ... directly at http://edge.media-server.com/m/p/mr4uxgas . A recorded replay of the ... live event and accessible at the links above until August ...
Breaking Medicine Technology: