Anticancer drug irinotecan

In addition, the activation of the anticancer drug irinotecan to its activeprincipal SN-38 occurs by CES2 [105-107], and its gastrointestinal toxicity has been associated with local SN-38 liberation in the gut mucosa [106]. 

Although chloroaromatics generally display lower reactivity in palladium-catalyzed reactions, the presence of the heteroatom in heteroaryl chlorides can activate the C—Cl bond in G-2 and C-4 positions. Accordingly, alkoxycarbonylation of S7 in the presence of the Pd(OAc)2/dppp catalyst followed by the annulation of the cyclopen-tanone ring was used for the construction of the tricyclic ring system (S9) during the total synthesis of the anticancer drug irinotecan [80]. 

It has been used to treat leukemia. Other anticancer drugs have been modified from Camptotheca acuminata. Topotecan is used to treat ovarian and small-lung cancers. Irinotecan is used to treat metastatic colorectal cancer. 

In a randomized, crossover study five patients with cancer taking irinotecan were given St. John s wort (32). The plasma concentrations of irinotecan significantly fell in the presence of the herbal remedy. The authors pointed out that this is likely to reduce the effectiveness of the anticancer drug. 

Yamamoto W, Verweij J, de Bruijn P, de Jonge MJ, Takano H, Nishiyama M, Kurihara M, Sparreboom A. Active transepithelial transport of irinotecan (CPT-11) and its metabolites by human intestinal Caco-2 cells. Anticancer Drugs 2001 12(5) 419-32. 

Mathijssen RH, Sparreboom A, Dumez H, van Oosterom AT, de Bruijn EA. Altered irinotecan metabolism in a patient receiving phenytoin. Anticancer Drugs 2002 13(2) 139-40. 

Ong SY, Clarke SJ, Bishop J, Dodds HM, Rivory LP. Toxicity of irinotecan (CPT-11) and hepato-renal dysfunction. Anticancer Drugs 2001 12(7) 619-25. 

A few years after the introduction of Taxol in 1996, further phytogenic anticancer drugs were launched to treat advanced cancers. Topotecan, marketed by Smith Kline Beecham under the trade name of Hycamtin, was approved by the FDA to treat ovarian cancers that have resisted other chemotherapy drugs. Furthermore, irinotecan was introduced by Pharmacia Upjohn under the trade name of Camptosar for the treatment of metastatic cancer of the colon or rectum. Both compounds are derivatives of camptothecin which was isolated from the Chinese tree Camptotheca acuminata, well known in Chinese Traditional Medicine for anticancer treatment [65]. Isolation of the bioactive principle camptothecin and its structure elucidation had already been performed in 1966... 

Anticancer drugs Atrasentan [139] Methotrexate [138] SN-38 (active metabolite of irinotecan) [139] ... 

Schmitt C, Blijham G, Jolain B, et al. Medical care consumption in a phase 111 trial comparing irinotecan with infusional 5-fluorouracil (5-FU) in patients with metastatic colorectal cancer after 5-FU failure. Anticancer Drugs 1999 10 617-623. 

Some of the clinically important drugs that have been identified to be mechanism-based CYP3A4 inhibitors include antibiotics (e g., erythromycin), anticancer drugs (e.g., irinotecan), antidepressants (e g., fluoxetine and paroxetine), anti-FIIV agents (e.g., ritonavir and... 

Anticancer drugs (chemotherapy and other) Irinotecan (Mathijssen et al. 2002), imatinib (Frye et al. 2004 Smith 2004)... 

Keywords Alkaloids topotecan anticancer drugs camptothecin irinotecan topoisomerase I ... 

Hajan R, Guan HT (2013) Speetrophotometric studies on the thermodynamics of the ds-DNA interaction with irinotecan for a better understanding of anticancer drug-DNA interactions. J Spectrosc. ID 380352. http //dx.doi.org/10.1155/2013/380352... 

Ion transfer, 14 (1977) 1 Irinotecan, anticancer agent, 34 (1997) 68 Isothermal titration calorimetry, in drug design, 38 (2001) 309... 

In recent years, however, some of the greatest emphasis has been placed on the search for anticancer and antiviral agents derived from natural products. Success in that area has not heen as great as that achieved in other helds. Since 1960, only seven plant-derived drugs have heen approved by the FDA for use as anticancer agents. Four of those drugs, vinblastine, vincristine, etoposide, and teniposide, were discovered in the 1950s. The last three—Taxol , topotecan, and irinotecan—were discovered and approved much more recently. 

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