SN-38 is an antineoplastic drug. It is the

active metabolite An active metabolite, or pharmacologically active metabolite is a biologically active metabolite of a xenobiotic substance, such as a drug or environmental chemical. Active metabolites may produce therapeutic effects, as well as harmful effects. ...

irinotecan Irinotecan, sold under the brand name Camptosar among others, is an anti-cancer medication used to treat colon cancer and small cell lung cancer. For colon cancer it is used either alone or with fluorouracil. For small cell lung cancer it is ...

(an analog of

camptothecin Camptothecin (CPT) is a topoisomerase inhibitor. It was discovered in 1966 by M. E. Wall and M. C. Wani in systematic screening of natural products for anticancer drugs. It was isolated from the Bark (botany), bark of ''Camptotheca acuminata'' (� ...

- a

topoisomerase I DNA topoisomerase 1 is an enzyme that in humans is encoded by the ''TOP1'' gene. It is a DNA topoisomerase, an enzyme that catalyzes the transient breaking and rejoining of a single strand of DNA. Function This gene encodes a DNA topoisomeras ...

inhibitor) but has 1000 times more activity than irinotecan itself. In vitro cytotoxicity assays show that the potency of SN-38 relative to irinotecan varies from 2- to 2000-fold. SN38 is formed via hydrolysis of irinotecan by

carboxylesterase The enzyme carboxylesterase (or carboxylic-ester hydrolase, EC 3.1.1.1; systematic name carboxylic-ester hydrolase) catalysis, catalyzes reactions of the following form: :a Ester, carboxylic ester + H2O \rightleftharpoons an Alcohol (chemistry), ...

s and metabolized via

glucuronidation Glucuronidation is often involved in drug metabolism of substances such as drugs, pollutants, bilirubin, androgens, estrogens, mineralocorticoids, glucocorticoids, fatty acid derivatives, retinoids, and bile acids. These linkages involve gly ...

UGT1A1 UDP-glucuronosyltransferase 1-1, also known as UGT-1A, is an enzyme that in humans is encoded by the ''UGT1A1'' gene. UGT-1A is a uridine diphosphate glucuronosyltransferase (UDP-glucuronosyltransferase, UDPGT or UGT), an enzyme of the glucuroni ...

. The variant of UGT1A1 in ~10% of Caucasians which leads to poor metabolism of SN-38 predicts irinotecan

toxicity Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacteria, bacterium, or plant, as well as the effect o ...

, as it is then less easily excreted from the body in its SN-38 glucuronide form. SN-38 and its glucuronide are lost into the bile and intestines. It can cause the symptoms of

diarrhoea Diarrhea (American English), also spelled diarrhoea or diarrhœa (British English), is the condition of having at least three loose, liquid, or watery bowel movements in a day. It often lasts for a few days and can result in dehydration d ...

and

myelosuppression Bone marrow suppression also known as myelotoxicity or myelosuppression, is the decrease in production of cells responsible for providing immunity (leukocytes), carrying oxygen (erythrocytes), and/or those responsible for normal blood clotting ( ...

experienced by ~25% of the patients administered

Interactive pathway map

References

Topoisomerase inhibitors {{Oncology-stub

Interactive pathway map

See also

References