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 Possible Therapeutic Target for the Treatment of HIV Infection
 SEATTLE, Aug. 9 /PRNewswire/ -- Cell Therapeutics, Inc. (CTI) today said that scientists from the Company presented data indicating that its small molecule compound, CT-2576, suppresses the cytokine-induced and tat-directed expression and replication of human immunodeficiency virus (HIV) in cells. The data was reported in a presentation today by Dr. David Leung, Director of the Company's Molecular Biology Program, at the Tenth International Conference on AIDS in Yokohama, Japan.
 Specifically, the Company said CT-2576 inhibited HIV expression by interfering with a specific species of a cell membrane phospholipid, called phosphatidic acid. Cell Therapeutics scientists have discovered that phosphatidic acid may constitute a unique intracellular "second messenger" pathway (named the Bursten Pathway by the Company) that, unlike previously described second messenger pathways, appears to be a stress pathway activated only in response to the presence of potentially cell-damaging or cell-threatening stimuli and not utilized by a cell for normal cellular processes.
 Cell Therapeutics has demonstrated that certain first messenger cytokines such as Interleukin-1 (IL-1) and Tumor Necrosis Factor (TNF), which bind to receptors imbedded in a cell membrane, induce the production of specific molecular species of phosphatidic acid implicated in cellular activation. Cell activation is one of the earliest steps in preparing a cell for a response such as cell division or production of inflammatory mediators.
 "Cellular activation and TNF appear to be closely involved in HIV expression and replication in cells. In fact, HIV possesses a protein called tat which 'transactivates' the host cell, playing a crucial role in viral replication," said Dr. James Bianco, chief executive officer of Cell Therapeutics. Company scientists reasoned that phosphatidic acid may be a common intracellular signal for both cytokine-induced and tat- directed expression and replication of HIV in cells."
 In the study, scientists from Cell Therapeutics developed and, in collaboration with the University of Minnesota and University of California Los Angeles, screened CT-2576 and other synthetic small molecule compounds known to be inhibitors of phosphatidic acid against a reporter gene expression system for their ability to inhibit HIV- expression in the chronically HIV-infected promonocyte U1 cell line. CT-2576 reduced phosphatidic acid generation in cells, blocking HIV-LTR promoter directed expression. CT-2576 had minimal effect on the expression of the "housekeeping gene," phosphoglycerase kinase, and cell toxicity. In additional studies, CT-2576 was highly effective at inhibiting the growth of a clinical isolate of HIV in fresh human blood mononuclear cells. In initial studies, CT-2576 was also found to be effective in inhibiting cytomegalovirus and SV40 early promoter activity. "Based on these early results, we believe that CT-2576 and other compounds of this class that can suppress the generation of this specific species of phosphatidic acid should be of therapeutic interest for delaying or preventing the onset of AIDS and certain other viral diseases in HIV-infected patients with greater specificity and safety than pharmaceuticals which inhibit normal second messenger pathways. We intend to proceed with the further development and evaluation of CT-2576 as a therapy to block HIV expression in chronically and freshly infected cells," Dr. Bianco said.
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 /CONTACT: James Bianco, M.D. of Cell Therapeutics, Inc., 206-282-7100; or Fred Spar of Kekst and Company, 212-593-2655/

CO: Cell Therapeutics, Inc. ST: Washington IN: MTC SU:

PS -- NY068 -- 4953 08/09/94 14:52 EDT
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Publication:PR Newswire
Date:Aug 9, 1994

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