Discovery of YM155, a novel survivin suppressant for the treatment of cancer

MEDI 312

Isao Kinoyama, isao.kinoyama@jp.astellas.com, Akira Matsuhisa, Takahito Nakahara, Masahiro Takeuchi, Kenna Shirasuna, Tsuyoshi Minematsu, Norio Asai, Shunichiro Matsumoto, Kenichi Kawaguchi, Junichi Kazami, Akira Toyoshima, Aya Kita, Fumiko Tominaga, Minoru Okada, and Mitsuaki Ohta. Drug Discovery Research, Astellas Pharma Inc, 21 Miyukigaoka, Tsukuba, Ibaraki, 305-8585, Japan
Survivin is a key member of the family of inhibitors of apoptosis (IAP) that suppress apoptosis through inhibition of caspases and procaspases. Survivin is selectively expressed in most solid tumors but not expressed in most normal tissues. Through the lead optimization of the HTS hit compound, we identified YM155 as a highly potent survivin suppressant. YM155 demonstrated antiproliferative activity against various human tumor cell lines, and induced in vivo antitumor activity without showing severe systemic toxicity in mice. YM155 is currently in Phase II clinical trials for the treatment of cancer. The syntheses and biological activities of YM155 derivatives will be presented.
 

Poster Session
7:00 PM-9:00 PM, Wednesday, August 22, 2007 BCEC -- Exhibit Hall - B2, Poster

Division of Medicinal Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007