ATM kinase inhibition may provide new class of HIV inhibitor Last Updated: 2005-04-18 16:30:38 -0400 (Reuters Health) By David Douglas NEW YORK (Reuters Health) - Inhibition of ataxia-dependent-mutated (ATM) kinase by the agent KU-55933 suppresses replication of wild-type and drug-resistant HIV-1 in vitro, UK researchers report in the May advance online issue of Nature Cell Biology. "Our work to date has focused on using KU-55933 in proof-of-concept studies in the research setting -- validating ATM as a novel target for treating HIV-1 infections," senior investigator Dr. Mark J. O'Connor told Reuters Health. This, he added, "represents a novel approach to anti-HIV therapy in that we are targeting a host protein and not a viral one." Dr. O'Connor of KuDOS Pharmaceuticals and colleagues note that the aim is to inhibit non-essential host cell proteins required for viral replication. ATM is such a protein, apparently not needed for host survival. Treating HIV-1 infected cells with the small molecule inhibitor KU-55933 leads to a deficiency in ATM kinase and retrovirus-induced cell death. As mentioned, the researchers found that KU-55933 represses replication of both wild-type and drug-resistant HIV-1. However, because of the novelty of this approach, Dr. O'Connor added, "ATM inhibitors will require further significant preclinical testing before we can conduct clinical studies." Nat Cell Biol 2005.
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