Description of Invention: Site-selective cAMP analogues that preferentially bind and activate PKA-I or PKA-II exhibit specificity not mimicked by parental cAMP. These analogues demonstrate a synergism of binding in appropriate combinations. 8-Cl-cAMP, which belongs to the ISD (isozyme site discriminator) class of site-selective cAMP analogues, activates and down-regulates PKA-I, but not PKA-II, by binding to both site A and B of RI and to site B of RII. 8-Cl-cAMP inhibits growth, in vitro and in vivo, in a broad spectrum of human carcinoma, fibrosarcoma, and leukemia cell lines without causing cytotoxicity. The growth-inhibitory effect of 8-Cl-cAMP correlates with the down-regulation of RI, the up-regulation of RII, and the suppression of c-myc and c-ras oncogene expression.
8-Cl-cAMP is a promising cancer chemotherapeutic agent that in preclinical studies can reverse the transformed phenotype of, and induce apoptotic cell death in, human cancer cells. Results of a Phase I clinical trial suggest that effective plasma levels (determined in preclinical studies) of 8-Cl-cAMP can be maintained below the maximum tolerated dose. More recently, the NCI has initiated and supported ongoing Phase I clinical trials of 8-Cl-cAMP for the treatment of colon cancer and multiple myeloma. The present invention provides compositions and methods for use of cAMP analogs, including 8-Cl-cAMP, as a therapeutic intervention for multiple human diseases.
Licensing Status: This technology is available for licensing on an exclusive or a non-exclusive basis. In addition to licensing, the technology is available for further development through collaborative research opportunities with the inventors.
Portfolios: Cancer Cancer - Therapeutics In-vivo Data
For Additional Information Please Contact: David Lambertson Ph.D. NIH Office of Technology Transfer 6011 Executive Blvd. Suite 325, Rockville, MD 20852 United States Email: firstname.lastname@example.org Phone: 301-435-4632 Fax: 301-402-0220