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Unique HTS assay capable of selecting compounds that work by mechanism other than inhibition of reverse transcriptase
CARY, NC and BIRMINGHAM, Ala. (Jan 15, 2008) - Trana Discovery, a drug discovery technology company, today announced that their recently-developed HIV high-throughput screening (HTS) assay designed to identify compounds that inhibit the use of transfer RNA (tRNA) by HIV has the ability to select compounds with anti-HIV bioactivity. Because tRNA is essential for HIV replication, disruption of the virus's ability to use tRNA appears to represent a novel target for anti-HIV therapy.
In a recent live cell-based study, a subset of compounds identified using the new Trana HIV 201 assay proved to inhibit the HIV virus through a mechanism other than inhibition of reverse transcriptase. The study was conducted in collaboration with and by Southern Research Institute.
Scientists at Trana Discovery have invested years of research to develop the patented technology that forms the basis for the assays used to screen molecular libraries for tRNA inhibitors. The technology centers on the anticodon stem loop (ASL) of tRNA and the importance of nucleotide modifications within the ASL. The ability to synthesize copies or mimics of the ASL with the modifications, just as they occur in nature, is what overcomes previous barriers to high-throughput screening and enables the application of Trana Discovery technology to rapidly and methodically search for inhibitors of tRNA.
During tests at the High Throughput Screening Center at Southern Research, several compounds were identified that responded to the assay. In a cell-based study that followed, a subset of these compounds was examined for their inhibition qualities in the replication of the HIV-1 Ba-L virus using live Peripheral Blood Mononuclear Cells (PBMC) and found to have anti-HIV activity. Further testing indicated that antiviral activity was not due to inhibition of reverse transcriptase, the mechanism of action of many of the currently available HIV therapies.
"The screen is interesting in that it identified compound classes that are different from that of known antivirals," said Lucile White, manager of the Southern Research High Throughput Screening Center. "As a consequence, this HTS assay may lead to the identification of leads which inhibit viral replication by a unique mechanism."
"The Trana HIV 201 assay gives pharmaceutical companies the ability to rapidly and efficiently screen vast libraries of compounds," said Steve Peterson, CEO of Trana Discovery. "For those companies that hold collections of bioactive compounds of an unknown mechanism of action, application of our assay could possibly help identify very quickly a totally new class of treatment for HIV. The fact that drug resistance continues to be a major challenge for managing patients with HIV and with increasing numbers of individuals who are being infected, we're very optimistic that the use of the assay will identify new antivirals to help keep patients one step ahead of the infection."
Trana Discovery is seeking partners holding diverse collections of compounds or compounds with known bioactivity against HIV but unknown mechanism of action to identify candidates for drug development. Organizations interested in licensing the Trana HIV 201 assay, which can screen up to 50,000 compounds per day, should contact Trana at info@tranadiscovery.com or by calling 866-390-3452 (toll free) or +1-919-342-6192. Parties interested in screening compounds using this assay at Southern Research Institute facilities may contact David Harris at d.harris@southernresearch.org or call +1-800-967-6774.
About Trana Discovery, Inc.
Trana Discovery, a drug discovery technology company, helps its partners find novel classes of drugs for the treatment of serious viral, fungal and bacterial infectious diseases. The technology identifies compounds that work through a unique mechanism of action: the target pathogen's ability to use transfer RNA (tRNA) in replication. The use of Trana Discovery technology can unlock the value - scientific, human, and financial - hidden in drug compound libraries, expedite the discovery of new drugs and provide opportunities for exclusive rights to new drug classes. Trana Discovery is commercializing technology that has been under development for nearly 20 years at North Carolina State University. The company is located in Cary, North Carolina. For more information, please visit www.tranadiscovery.com.
About Southern Research Institute
Southern Research Institute is a not-for-profit organization that conducts basic and applied research in drug discovery and preclinical drug development, advanced engineering, energy production and environmental areas. To date, Southern Research has discovered six FDA-approved cancer drugs, an unsurpassed record in the pharmaceutical industry. In addition, Southern Research has discovered six drugs that are currently in late-stage development or clinical trials and has evaluated approximately 50 percent of all FDA-approved cancer drugs. For more information, please visit www.southernresearch.org.