Antitumor Norindenoisoquinoline Topoisomerase 1 Inhibitors

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Topoisomerase enzymes 1 and 2 are responsible for changing the structure of DNA during the cell cycle. The DNA has to be reorganized and opened during DNA synthesis. In cancer cells and other healthy proliferating cells, topoisomerase enzymes are more active than slower growing or terminally differentiated cells. Medicinal chemists have used this knowledge to create inhibitors of these enzymes in hope of reducing symptoms or completely eradicating a tumor. A topoisomerase 1 (TOP1) inhibitor named norindenoisoquinoline AI-III-52 was synthesized and found to have anticancer activity in vitro that was comparable to the gold standard of topoisomerase inhibitors, camptothecin. The issue with this new drug was that it had strong hydrophobicity, which hindered the development and bioavailability for the patient. Cancer cells also showed the ability to remove this drug by efflux pumps, reducing its effectiveness at treating the disease.

Purdue University researchers have synthesized water-soluble norindenoisoquinolines that have increased stability and reduced reversibility of the drug-target interaction. In addition, this new drug will overcome some of the previous cases of drug resistance. In in vitro toxicology assays, these new compounds are highly potent to leukemia, melanoma, lung, colon, brain, breast, ovarian, prostate, and kidney cancers.

Advantages:
-Water soluble
-Increased stability and bioavailability
-Topoisomerase 1 is a proven target for cancer therapy

Potential Applications:
-Medical/Healthcare
-Pharmaceuticals
-Drug Development
-Cancer Treatment
Jul 26, 2012
NATL-Patent
United States
9,206,193
Dec 8, 2015

Jan 27, 2011
PCT-Patent
WO
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Jan 27, 2011
NATL-Patent
Australia
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Jan 27, 2011
NATL-Patent
European Patent
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Jan 27, 2011
NATL-Patent
Canada
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Jan 27, 2010
Provisional-Patent
United States
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Purdue Office of Technology Commercialization
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Email: otcip@prf.org