Alfacell and University of Bath Collaborators Identify Structure of Amphinase
BLOOMFIELD, N.J., May 29, 2007 /PRNewswire-FirstCall/ -- Alfacell Corporation today announced that an international collaboration between its scientists and members of Prof. K. Ravi Acharya's research group with the Department of Biology and Biochemistry at the University of Bath in the United Kingdom has identified the enzymatic, physical and three-dimensional properties of Amphinases, a novel group of enzymes that kill tumor cells in vitro. These findings demonstrate that Amphinases evade the mammalian ribonuclease (RNase) inhibitor, which points to their therapeutic potential.
Published online in the Journal of Molecular Biology on May 10, 2007 (Singh U.P. et al., 2007, doi:10.1016/j.jmb.2007.04.071) this seminal paper summarizes the findings and expands on results previously presented at the 6th International Conference on Ribonucleases (Bath, UK, 2002). The Amphinases possess structural similarities with Alfacell's flagship anti-cancer drug candidate, ONCONASE(R) (ranpirnase). Despite the structural similarities to ONCONASE, high-resolution X-ray crystal structures of one amphinase variant, Amph-2, in both natural and recombinant forms, reveal a collection of unique features at the catalytic center (some integral, some peripheral). The paper also provides valuable information for researchers studying the evolutionary diversity of amphibian RNase A homologues, an intriguing class of enzymes with potential clinical applications.
"We are proud and excited to be able to introduce by way of a full characterization yet another novel and important enzyme to the scientific community," said Kuslima Shogen, Alfacell's chairman and chief executive officer. "Our collaborative efforts with Dr. Acharya's team resulted in high resolution crystal structures of this exciting family of primordial pluripotent enzymes. Amphinase is the second anti-tumor ribonuclease to be isolated from Rana pipiens oocytes, and is currently undergoing preclinical testing for the investigation of numerous potential therapeutic opportunities."
ONCONASE is a first-in-class therapeutic product candidate based on Alfacell's proprietary ribonuclease (RNase) technology. A natural protein isolated from the leopard frog, ONCONASE has been shown in the laboratory and clinic to target cancer cells while sparing normal cells. ONCONASE triggers apoptosis, the natural death of cells, via multiple molecular mechanisms of action.
About Alfacell Corporation
Alfacell Corporation is the first company to advance a biopharmaceutical product candidate that works in a manner similar to RNA interference (RNAi) through late-stage clinical trials. The product candidate, ONCONASE, is an RNase that overcomes the challenges of targeting RNA for therapeutic purposes while enabling the development of a new class of targeted therapies for cancer and other life-threatening diseases. In addition to an ongoing Phase IIIb study in malignant mesothelioma, Alfacell is conducting a Phase I/II trial of ONCONASE in non-small cell lung cancer (NSCLC) and other solid tumors. For more information, visit http://www.alfacell.com.
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Posted: May 2007