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.
Advantages
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
Therapeutic drugs.
Stage of Development
Currently, actinonin analogs with improved solubility and inhibitory capacity are being investigated.
Lead Inventors
Dr. William G. Bornmann
Dr. David A. Scheinberg
Patent Information
- US patent 6,660,741.
- PCT application published as WO 02/074050.
- Patent prosecution ongoing in Europe, Australia, and Japan.
References
Lee MD, et al. J Clin Invest. 114:1107-1116 (2004).
Contact Information
Viviane Martin, PhD
Tel: 212-639-6181; Fax: 212-717-3439
E-mail: martinv@mskcc.org
