Analogs of Actinonin as Antitumor Compounds

SK 934

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

Actinonin analogs with improved solubility and inhibitory capacity currently being investigated

Lead Inventors

  • William G. Bornmann, PhD
  • David A. Scheinberg, MD, PhD, Program Chair and Laboratory Head, Molecular Pharmacology & Chemistry Program, Sloan Kettering Institute, Memorial Sloan Kettering

Patent Information

U.S. patent issued: 6, 887, 887

References

Lee MD, et al. (2004) J Clin Invest. 114:1107-1116

Contact Information

Yashodhara Dash, MBBS, PhD, MBA
Director, Technology Management and Commercialization
Tel: 646-888-1073
E-mail: dashy@mskcc.org

 

Stage of Development
In vitro
Indications