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.
Stephen Fesik (Abbott Laboratories, Abbott Park, IL, USA)
Online publication can be accessed by clicking here.
(C) Nature press release.
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