Breast Cancer Drug Discovery with Combinatorial Chemical Libraries.
Annual rept. 2 Sep 97-1 Sep 98
ARIZONA UNIV TUCSON
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The goal of this project is to discover new drugs that have specificity and significant anticancer activity against breast cancer. The approach uses several novel aspects that permit high volume screening for drug discovery. To maximize the number of unique chemical compounds available for testing, we have employed the new technology of combinatorial chemistry to produce large libraries containing thousands of compounds using the one-bead, one compound technology in which a portion of each compound can be released in vitro in a semisolid agarose culture of breast cancer and other tumor types as controls 1-3. During the past year, we have screened two large libraries and discovered three lead compounds that showed relative specificity against breast cancer cell lines. Work is underway in our laboratories to confirm their activities. Compound A4 was discovered during the first year of this grant. Preliminary preclinical studies indicate that A4 has in vivo anti-breast cancer activity human xenograft SCID mouse model, it is non-myelosuppressive and is well tolerated by the mouse. During the coming year, well continue to develop A4 and at the same time characterize the three new leads
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