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
Schools and Departments: School of Life Sciences > Chemistry
Subjects: Q Science > QD Chemistry > QD0241 Organic chemistry
Depositing User: Tristan Reuillon
Date Deposited: 15 Jan 2016 15:34
Last Modified: 08 Mar 2017 05:58
URI: http://sro.sussex.ac.uk/id/eprint/59234

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