Summary of Invention
The natural product peptidimetic actinonin demonstrates antiproliferative, antiangiogenic, and antimetastatic properties against many human cancers, including leukemia and lymphoma, as well as against lung and prostate tumors, both in vitro and in vivo. An improved method for the asymmetric synthesis of (S,S,R)-(-)-actinonin allows for inexpensive and abundant production of this compound and novel analogs.
Actinonin and actinonin analogs were assayed for cytotoxity in human prostate, lymphoma, and acute myeloid leukemia cells. Actinonin and some of its analogs are remarkably cytotoxic in the µM range against all the cancer cell lines tested.
Although actinonin is commercially available and usually extracted from bacteria, the yield of actinonin derived in this way is miniscule. The present synthetic pathway improves the synthesis of actinonin and allows for the synthesis of novel analogs, which may have improved efficacy.
Areas of Application
Stage of Development
Actinonin analogs with improved solubility and inhibitory capacity currently being investigated
U.S. patents issued:
Lee MD, et al. (2004) J Clin Invest. 114:1107-1116
Lisa Placanica, PhD
Tel: 212-639-6181; Fax: 212-717-3439