Cyclic Peptide Antitumor Agents

Novel Peptide Compounds with Enhanced Anti-Tumor Activity NU 2004-095, NU 2003-053, NU 2002-081 Inventors Thomas Adrian Wenxin Gu Shouxin Liu Richard Silverman* Gerald Soff Short Description Synthesis of a novel family of peptide compounds with increased anti-proliferative activity Abstract Northwestern researchers have synthesized novel peptides based upon natural marine products that exhibit cytotoxicity against a variety of cancer cells lines. Sansalvamide A and Scytalidamide A are two such natural products. The inventors created cyclic peptide analogs that display greater anticancer activity compared to these known growth inhibitors. Importantly, the analogs also exhibit an 80-fold reduction in effective dosage with greater efficacy. The scientists have developed an efficient solid phase synthesis of the cyclic peptides, creating a series of compounds that have already been successfully tested in vitro across several human cancer cells lines, including prostate cancer, breast cancer, melanoma, and colon cancers. Applications Therapeutics: Anti-Cancer Advantages Enhanced anti-proliferative activity Improved dosage efficacy Efficient solid phase synthesis of compounds Effective against a variety of cancer cell lines Publications Liu S, Gu W, Lo D, Ding XZ, Ujiki M, Adrian TE, Soff GA, Silverman RB (2005) N-methylsansalvamide a peptide analogues. Potent new antitumor agents. Journal of Medicinal Chemistry 48: 3630-38. Ujiki MB, Milam B, Ding XZ, Roginsky AB, Salabat MR, Talamonti MS, Bell RH, Gu W, Silverman RB, Adrian TE (2006) A novel peptide sansalvamide analogue inhibits pancreatic cancer cell growth through G0/G1 cell-cycle arrest. Biochemical & Biophysical Research Communications 340: 1224-1228. IP Status Issued US Patent No. 7,709,443 Contact Information Allan Nader, PhD Invention Manager (p) (847) 491-4456 (e) a-nader@northwestern.edu