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- W2000366629 abstract "1. Irinotecan (also known as CPT-11) is a water soluble, semi-synthetic analogue of 20(S)camptothecin (CPT) with promising activity against a range of tumour types. 2. As with all other active analogues of CPT, irinotecan causes cell toxicity by stabilizing a ternary complex between the nuclear enzyme topoisomerase I (topo I) and doublestranded DNA. This leads to replication fork-arrest, double DNA strand breaks and, possibly, illegitimate recombination of vital genes. 3. This activity is much greater for its metabolite SN-38 and irinotecan is widely considered to be a prodrug of SN-38. 4. The anti-topo I activity of CPT is stereoselective at C-20 and irinotecan is synthesized from 20(S)CPT to ensure maximal activity. In aqueous solutions, the lacton ring of CPT under goes reversible and spontaneous hydrolysis to a ring-opened and inactive carboxylate form. In patients, it has been shown that the lactone is the predominant form of SN-38 in plasma, whereas the opposite is true for irinotecan. 5. The transformation of irinotecan to SN-38 is catalysed by carboxylesterases. However, this conversion appears relatively inefficient in man. 6. Irinotecan and SN-38 show evidence of other metabolic reactions (type I and II), some of which could be subject to pharmacogenetic variablity. 7. Therapy with irinotecan is associated with unusual toxicities, such as an acute cholinergic-like syndrome and delayed onset diarrhoea. Although the mechanism for the diarrhoea remains to be defined, the cholinergic toxicity appears to be due to an inhibition of acetylcholinesterase." @default.
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- W2000366629 date "1996-11-01" @default.
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- W2000366629 title "IRINOTECAN (CPT-11): A BRIEF OVERVIEW" @default.
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- W2000366629 doi "https://doi.org/10.1111/j.1440-1681.1996.tb01158.x" @default.
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