Potent, Easy to Use Targeted Toxins as Anti-Tumor Agents
Posted Jun 15 2010 5:00pm
Description of Invention: The invention discloses synthesis and use of novel derivatives of 2-[2'-(2-aminoethyl)-2-methyl-ethyl]-l,2-dihydro-6-methoxy-3H-dibenz-[de,h]isoquinoline-l,3-dione as targeted anti-tumor agents. The use of targeted toxin conjugates with anti-cancer antibodies, such as herceptin, is increasing. Based on a comparison with the structurally complex toxins, such as DM1, available in the market, these novel toxins are more stable in circulation, thus making the toxin-conjugates more tumor-selective and less toxic. As such, these compounds are superior alternatives to the existing toxins.
The invention describes a potent and easy to synthesize toxin that can be used for generating a variety of prodrugs. These compounds can be attached to a ligand that recognizes a receptor on cancer cells, or to a peptide that is cleaved by tumor-specific proteases. The compounds are topoisomerase inhibitors and are mechanistically different from DM1 that targets tubulin.
The structure of the toxin allows it to be modified with a peptide linker that is stable, but rapidly cleaved in lysosomes after the compound is specifically taken up by cancer cells.
Applications: The compounds can be used for preparation of a variety of potent anti-cancer agents with low systemic toxicity.
Easy to prepare
Structural features make these compounds more stable in circulation
Toxin conjugates are more tumor-selective and less toxic
Development Status: In vitro studies are completed and in vivo animal model studies are ongoing.
Inventors: Nadya I Tarasova (NCI) Marcin D Dyba (NCI) Christophr J Michejda (NCI)
Portfolios: Cancer Cancer - Therapeutics In-vivo Data In-vitro Data
For Additional Information Please Contact: Jennifer Wong NIH Office of Technology Transfer 6011 Executive Blvd. Suite 325, Rockville, MD 20852 United States Email: email@example.com Phone: 301-435-4633 Fax: 301-402-0220