Morton_1999_Cancer.Res_59_1458

Reference

Title : The anticancer prodrug CPT-11 is a potent inhibitor of acetylcholinesterase but is rapidly catalyzed to SN-38 by butyrylcholinesterase - Morton_1999_Cancer.Res_59_1458
Author(s) : Morton CL , Wadkins RM , Danks MK , Potter PM
Ref : Cancer Research , 59 :1458 , 1999
Abstract :

Patients treated with high doses of CPT-11 rapidly develop a cholinergic syndrome that can be alleviated by atropine. Although CPT-11 was not a substrate for acetylcholinesterase (AcChE), in vitro assays confirmed that CPT-11 inhibited both human and electric eel AcChE with apparent K(i)s of 415 and 194 nM, respectively. In contrast, human or equine butyryl-cholinesterase (BuChE) converted CPT-11 to SN-38 with K(m)s of 42.4 and 44.2 microM for the human and horse BuChE, respectively. Modeling of CPT-11 within the predicted active site of AcChE and BuChE corroborated experimental results indicating that, although the drug was oriented correctly for activation, the constraints dictated by the active site gorge were such that CPT-11 would be unlikely to be activated by AcChE.

PubMedSearch : Morton_1999_Cancer.Res_59_1458
PubMedID: 10197614

Related information

Inhibitor SN-38    Irinotecan
Substrate SN-38    Irinotecan    Irinotecan

Citations formats

Morton CL, Wadkins RM, Danks MK, Potter PM (1999)
The anticancer prodrug CPT-11 is a potent inhibitor of acetylcholinesterase but is rapidly catalyzed to SN-38 by butyrylcholinesterase
Cancer Research 59 :1458

Morton CL, Wadkins RM, Danks MK, Potter PM (1999)
Cancer Research 59 :1458