Navigation Links
Anthrax inhibitors identified by Burnham team

A collaborative team of scientists led by The Burnham Institute's Maurizio Pellecchia, Ph.D., has identified inhibitors of the anthrax toxin, termed lethal factor ("LF") that could be developed into an emergency treatment for exposure to inhalation anthrax. These findings will be published by the Proceedings of the National Academy of Sciences by Early Edition at the journal's website the week of June 20th.

Bacillus anthracis ("anthrax") is a proven agent of biological terrorism. Pulmonary anthrax, in which spores of the anthrax bacteria are inhaled, is typically fatal unless diagnosis is made at an early stage of infection, when antibiotics such as Ciprofloxacin can provide a complete cure. At late stages in the disease, antibiotics can kill the anthrax bacteria, but do not affect LF secreted by the bacteria, which is sufficiently concentrated in the bloodstream. LF enters cells and inactivates a human protein called "mitogen-activated protein kinase", or "MAPKK", disrupting the normal signaling pathways of the cell and inducing cell-death.

Using a fragment-based approach based on assays conducted with highly sensitive nuclear magnetic resonance ("NMR") techniques developed in Dr. Pellecchia's laboratory, the scientists were able to identify a scaffold that served as a template for designing a preferred structure for small-molecule inhibitors of LF. Lead compounds were synthesized and validated as highly potent and selective against LF in vitro. In in vitro assays, the compounds did not affect prototype human metalloproteinase enzymes that are structurally similar to LF. This is very important as selectivity is a fundamental prerequisite for a drug to be safe for use in humans.

Three lead compounds where tested in mice infected with anthrax spores, in combination with the antibiotic Ciprofloxacin. The survival rate for mice treated with each of the compounds tested in the combination therapy was two-fold over mice treated with Ciprofloxacin a lone.

"This represents a significant advance in developing a possible emergency treatment for anthrax," said Dr. Pellecchia. "We are working on refining the chemical structure of the compound with the goal of achieving an even more potent and selective drug that should exhibit a higher degree of protection against anthrax."

This research was supported by grants from the National Institute of Allergy and Infectious Diseases, from the National Institutes of Health.

Coauthors on this study include:

Martino Forino, Sherida Johnson, Tian Y. Wong, Dimitri V. Rozanov, Alexei Y. Savinov, Wei Li, Roberto Fattorusso, Barbara Becattini, and Dawoon Jung, from The Burnham Institute.
Robert Liddington, Ph.D., Acting Director, Center for Infectious and Inflammatory Diseases at The Burnham Institute;
Alex Strongin, Ph.D., Professor, Cell Adhesion/Extracellular Matrix Program, The Burnham Institute;
Jeffrey Smith, Ph.D., Professor, and Director of the Center for Proteolytic Pathways at The Burnham Institute;
Ruben A. Abagyan, Ph.D., Professor, and Andrew J. Orry, Molecular Biology Department at The Scripps Research Institute;
Ken Alibek, Ph.D., National Center for Biodefense, George Mason University, Fairfax, Virginia.

###

The Burnham Institute, founded in 1976, is an independent not-for-profit biomedical research institution dedicated to advancing the frontiers of scientific knowledge and providing the foundation for tomorrow's medical therapies. The Institute is home to three major centers: the original Cancer Center, the Del E. Webb Neuroscience and Aging Center established in 1999, and the Infectious and Inflammatory Disease Center dedicated in 2004. Since 1981, the Institute's Cancer Center has earned the prestigious designation as a Non-comprehensive Cancer Center by the National Cancer Institute. Discoveries by Burnham scientists have contributed to the development of new drugs for Alzheimer's disea se, heart disease and several forms of cancer. Today the Burnham Institute employs over 700, including more than 550 scientists. The majority of the Institute's funding derives from federal sources, but private philanthropic support is essential to continuing bold and innovative research. For additional information about the Institute and ways to support the research efforts of the Institute, visit www.burnham.org.


'"/>

Source:Burnham Institute


Related biology news :

1. Study Models Impact Of Anthrax Vaccine
2. Anthrax test, developed by army and CDC, receives FDA approval
3. Anthrax stops body from fighting back, study shows
4. Anthrax spores may survive water treatment
5. Anthrax inhibitor counteracts toxin, may lead to new therapeutics
6. Anthrax attack posed greater potential threat than thought
7. Anthrax paralyzes immune cells with lethal toxin, UF research shows
8. Protease inhibitors reach beyond HIV
9. Enzyme inhibitors block replication of SARS virus
10. Sweet water taste paradoxically predicts sweet taste inhibitors
11. COX-2 inhibitors significantly reduce risk of cancer
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:1/22/2016)... January 22, 2016 ... addition of the  "Global Behavioral Biometric ... --> http://www.researchandmarkets.com/research/4lmf2s/global_behavioral ) has ... Behavioral Biometric Market 2016-2020"  report to ... and Markets ( http://www.researchandmarkets.com/research/4lmf2s/global_behavioral ) has announced ...
(Date:1/21/2016)... --> ... report "Emotion Detection and Recognition Market by Technology (Bio-Sensors, NLP, ... Voice Recognition and Others), Services, Application Areas, End ... published by MarketsandMarkets, the global Emotion Detection and ... Billion by 2020, at a CAGR of 31.9%, ...
(Date:1/20/2016)... , Jan. 20, 2016   MedNet Solutions ... the entire spectrum of clinical research, is pleased to ... MedNet,s significant achievements are the result of the company,s ... iMedNet eClinical , it,s comprehensive, easy-to-use and ... --> Key MedNet growth achievements in ...
Breaking Biology News(10 mins):
(Date:2/12/2016)... SOUTH PLAINFIELD, N.J. , Feb. 12, 2016 ... today announced the second annual STRIVE (Strategies to ... for Duchenne muscular dystrophy (DMD). STRIVE provides funds ... collaborative programs that will make meaningful contributions to ... education or fostering development of future patient advocates. ...
(Date:2/11/2016)... SAN DIEGO, Feb. 11, 2016  Neurocrine Biosciences, Inc. (NASDAQ: ... year ended December 31, 2015. --> ... reported a net loss of $29.3 million, or $0.34 loss per ... loss per share for the same period in 2014. For the ... of $88.9 million, or $1.05 loss per share, as compared to ...
(Date:2/11/2016)...  Bioethics International, a not-for-profit organization focused on the ethics ... made accessible to patients around the world, today announced that ... publication of the Good Pharma Scorecard an ... as one of BMJ Open ,s ,Most Popular Articles, ... most frequently read. Ed Sucksmith , assistant editor ...
(Date:2/11/2016)... ... February 11, 2016 , ... ... on the development and manufacture of biopharmaceuticals and therapeutics, announces an agreement ... 2016 BioProcess International Awards – Recognizing Excellence in the People, Organizations and ...
Breaking Biology Technology: