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Re-engineering of the Duocarmycin Structural Architecture Enables Bioprecursor Development Targeting CYP1A1 and CYP2W1 for Biological Activity
Sheldrake, Helen M. Travica, S. Johansson, I. Elsalem, Lina M.I. Illingworth, Nicola A. Cresswell, Alexander J. Reuillon, Tristan
Sheldrake, Helen M.
Travica, S.
Johansson, I.
Elsalem, Lina M.I.
Illingworth, Nicola A.
Cresswell, Alexander J.
Reuillon, Tristan
Publication Date
2013-08-08
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© 2013 American Chemical Society. This is an Open Access article
licensed under the Creative Commons CC-BY-NC-ND license (http://pubs.acs.org/page/policy/authorchoice_ccbyncnd_termsofuse.html)
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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.
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Sheldrake HM, Travica S, Johansson I et al (2013) Re-engineering of the Duocarmycin
Structural Architecture Enables Bioprecursor Development Targeting CYP1A1 and CYP2W1 for
Biological Activity. Journal of Medicinal Chemistry. 56(15): 6273-6277.
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