SN-38

SN-38 is an antineoplastic drug. It is the active metabolite of irinotecan (an analog of camptothecin - a topoisomerase I 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.[1]

SN-38
Names
Preferred IUPAC name
(4S)-4,11-Diethyl-4,9-dihydroxy-1,4-dihydro-3H,14H-pyrano[3′,4′:6,7]indolizino[1,2-b]quinoline-3,14-dione
Other names
7-Ethyl-10-hydroxycamptothecin
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.171.154
UNII
  • InChI=1S/C22H20N2O5/c1-3-12-13-7-11(25)5-6-17(13)23-19-14(12)9-24-18(19)8-16-15(20(24)26)10-29-21(27)22(16,28)4-2/h5-8,25,28H,3-4,9-10H2,1-2H3/t22-/m0/s1 checkY
    Key: FJHBVJOVLFPMQE-QFIPXVFZSA-N checkY
  • O=C\1N4\C(=C/C2=C/1COC(=O)[C@]2(O)CC)c3nc5c(c(c3C4)CC)cc(O)cc5
Properties
C22H20N2O5
Molar mass 392.404 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N verify (what is checkY☒N ?)
Infobox references

SN38 is formed via hydrolysis of irinotecan by carboxylesterases and metabolized via glucuronidation by UGT1A1.

The variant of UGT1A1 in ~10% of Caucasians which leads to poor metabolism of SN-38 predicts irinotecan toxicity, as it is then less easily excreted from the body in its SN-38 glucuronide form.[2]

SN-38 and its glucuronide are lost into the bile and intestines. It can cause the symptoms of diarrhoea and myelosuppression experienced by ~25% of the patients administered irinotecan.

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles. [§ 1]

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IrinotecanPathway_WP46359
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IrinotecanPathway_WP46359
|alt=Irinotecan Pathway edit]]
Irinotecan Pathway edit
  1. The interactive pathway map can be edited at WikiPathways: "IrinotecanPathway_WP229".

See also

References
  1. http://labeling.pfizer.com/ShowLabeling.aspx?id=533
  2. O'Dwyer PJ, Catalano RB (October 2006). "Uridine diphosphate glucuronosyltransferase (UGT) 1A1 and irinotecan: practical pharmacogenomics arrives in cancer therapy". J. Clin. Oncol. 24 (28): 4534–8. doi:10.1200/JCO.2006.07.3031. PMID 17008691.


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