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

Helen M. Sheldrake, Sandra Travica, Inger Johansson, Paul M. Loadman, Mark Sutherland, Lina Elsalem, Nicola Illingworth, Alexander J. Cresswell, Tristan Reuillon, Steven D. Shnyder, Souren Mkrtchian, Mark Searcey, Magnus Ingelman-Sundberg, Laurence H. Patterson, Klaus Pors

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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.
Original languageEnglish
Pages (from-to)6273-6277
Number of pages5
JournalJournal of Medicinal Chemistry
Issue number15
Publication statusPublished - 11 Jul 2013

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