Re-engineering of the duocarmycin structural architecture enables bioprecursor development targeting CYP1A1 and CYP2W1 for biological activity

Sheldrake, Helen M., Travica, Sandra, Johansson, Inger, Loadman, Paul M., Sutherland, Mark, Elsalem, Lina, Illingworth, Nicola, Cresswell, Alexander J., Reuillon, Tristan, Shnyder, Steven D., Mkrtchian, Souren, Searcey, Mark, Ingelman-Sundberg, Magnus, Patterson, Laurence H. and Pors, Klaus (2013) Re-engineering of the duocarmycin structural architecture enables bioprecursor development targeting CYP1A1 and CYP2W1 for biological activity. Journal of Medicinal Chemistry, 56 (15). pp. 6273-6277. ISSN 0022-2623

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Abstract

A library of duocarmycin bioprecursors based on the CPI and CBI scaffolds was synthesized and used to probe selective activation by cells expressing CYP1A1 and 2W1, CYPs known to be expressed in high frequency in some tumors. Several CPI-based compounds were pM–nM potent in CYP1A1 expressing cells. CYP2W1 was also shown to sensitize proliferating cells to several compounds, demonstrating its potential as a target for tumor selective activation of duocarmycin bioprecursors.

Item Type:	Article
Faculty \ School:	Faculty of Science > School of Pharmacy (former - to 2024)
UEA Research Groups:	Faculty of Science > Research Groups > Medicinal Chemistry (former - to 2017) Faculty of Science > Research Groups > Chemical Biology and Medicinal Chemistry (former - to 2021)
Depositing User:	Pure Connector
Date Deposited:	20 Aug 2013 05:29
Last Modified:	28 Mar 2025 05:15
URI:	https://ueaeprints.uea.ac.uk/id/eprint/43143
DOI:	10.1021/jm4000209

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