Rubitecan ( INN, trade name Orathecin) is an oral

topoisomerase DNA topoisomerases (or topoisomerases) are enzymes that catalyze changes in the topological state of DNA, interconverting relaxed and supercoiled forms, linked (catenated) and unlinked species, and knotted and unknotted DNA. Topological issues in ...

inhibitor, developed by SuperGen (now Astex Pharmaceuticals, a member of the Otsuka Group).

History

On January 27, 2004, SuperGen announced that it has completed the submission of an NDA for rubitecan to the US FDA, and was accepted for filing in March 2004. In January 2005, and under the direction of then-CEO James Manuso, SuperGen withdrew the NDA for rubitecan, based on feedback indicating that the current data package would not be sufficient to gain US approval, and in January 2006, the Marketing Authorization Application (MAA) filed with the

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of pharmaceutical products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products ...

(EMA) was also withdrawn. The name rubitecan is a portmanteau of SuperGen's founder, Joseph Rubinfeld, and the chemical name 9-nitrocamptothecin.

Synthesis

Large scale production of rubitecan has encountered problems. The direct nitration of camptothecin results in regioselectivity problems. One way that has been used to synthesize Rubitecan is to nitrate 10-hydroxycamptothecin then remove the hydroxyl functional group.

Use as anticancer drug

Rubitecan is a compound used extensively in cancer research. Rubitecan is an effective drug against pancreatic cancer and other solid tumors. One major problem is the lack of oral bioavailability due to low permeability and poor water solubility. One study shows 9-NC-SD through Soluplus1-based solid dispersion system is a much more effective delivery method than free 9-NC.

References

{{Chemotherapeutic agents Abandoned drugs Topoisomerase inhibitors