Rubitecan

Rubitecan, marketed by Supergen as Orathecin, is a promising oral treatment for solid melanoma, prostate, breast, ovarian, and other cancers, as well as leukemia. It is a derivative of camptothecin, a topoisomerase inhibitor known from Chinese Traditional Medicine. It selectively targets the critical S-stage of cellular reproduction – particularly in acidic environments, as in many cancer cells – relaxing DNA supercoiling and generating lethal breaks in the DNA. Due to insolubility, its biological delivery mechanism is not yet effective, and it has not been approved for clinical use.

https://www.sciencedirect.com/topics/medicine-and-dentistry/rubitecan
https://en.wikipedia.org/wiki/Rubitecan
https://en.wikipedia.org/wiki/Topoisomerase_inhibitor
https://en.wikipedia.org/wiki/Camptothecin#cite_note-Y.Pommier_2003-14
https://www.ncbi.nlm.nih.gov/pubmed/1995300

Rubitecan is a DNA topoisomerase I inhibitor. It inhibits DNA topoisomerase I and increases the fraction of supercoiled DNA in a cell-free assay in a concentration-dependent manner. Rubitecan inhibits the growth of A121 ovarian and H460 lung cancer cells (IC₅₀s = 4 and 2 nM, respectively). It also inhibits the growth of doxorubicin-susceptible and -resistant MCF-7 breast cancer cells (IC₅₀s = 2 and 3 nM, respectively). Rubitecan (4 mg/kg twice per week) reduces tumor growth in a U937 leukemia mouse xenograft model.

Yellow Amorphous Powder

Semisynthetic camptothecin which inhibits DNA topoisomerase I. Prodrug of 9-aminocamptothecin. Antineoplastic.

ChEBI: A pyranoindolizinoquinoline that is camptothecin in which the hydrogen at position 9 has been replaced by a nitro group. It is a prodrug for 9-aminocamptothecin.

[1] E RUBIN. Identification of a mutant human topoisomerase I with intact catalytic activity and resistance to 9-nitro-camptothecin.[J]. The Journal of Biological Chemistry, 1994, 269 4: 2433-2439.
[2] H R HINZ. Pharmacokinetics of the in vivo and in vitro conversion of 9-nitro-20(S)-camptothecin to 9-amino-20(S)-camptothecin in humans, dogs, and mice.[J]. Cancer research, 1994, 54 12: 3096-3100.
[3] R. BERNACKI. In Vitro Antitumor Activity of 9‐Nitro‐Camptothecin as a Single Agent and in Combination with other Antitumor Drugs[J]. Annals of the New York Academy of Sciences, 2000, 922 1. DOI: 10.1111/j.1749-6632.2000.tb07046.x
[4] P. PANTAZIS. 9-nitro-camptothecin delays growth of U-937 leukemia tumors in nude mice and is cytotoxic or cytostatic for human myelomonocytic leukemia lines in vitro[J]. European Journal of Haematology, 1993, 50 2: 81-89. DOI: 10.1111/j.1600-0609.1993.tb00146.x