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A promising approach to eliminate cancer cells is to trigger cell death (apoptosis) with inhibitors that bind to and block anti-apoptotic proteins that help keep cancer cells alive - as reported in an advanced online publication in Nature. A newly discovered small-molecule inhibitor, called ABT-737, interferes with anti-apoptotic proteins to kill certain cancer cells directly and greatly enhance the effectiveness of chemotherapy, say the researchers.
Proteins that inhibit apoptosis, such as Bcl-XL, Bcl-2, and Bcl-w, play a role in tumour formation, growth and resistance to treatment. Stephen Fesik and colleagues used a sophisticated nuclear-magnetic-resonance-based method of identifying lead compounds to screen a library of chemicals, isolate a promising small molecule and modify it to produce ABT-737. The inhibitor binds to these anti-apoptotic proteins with an affinity two to three orders of magnitude greater than any previously reported molecule. ABT-737 alone was found to effectively kill certain cancer cell lines, including lymphoma and small-cell lung carcinoma (SCLC) lines, and to enhance the effects of chemotherapy and radiation on other cancer cell lines. Importantly, in a mouse model, ABT-737 by itself caused complete regression of human SCLC tumour xenografts. Author contact: Stephen Fesik (Abbott Laboratories, Abbott Park, IL, USA)
E-mail: Stephen.Fesik@abbott.com Online publication can be accessed by clicking here. (C) Nature press release.
Message posted by: Trevor M. D'Souza
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