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Re-engineering of the duocarmycin structural architecture enables bioprecursor development targeting CYP1A1 and CYP2W1 for biological activity
journal contribution
posted on 2023-06-08, 23:59 authored by 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 PorsA 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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Publication status
- Published
File Version
- Published version
Journal
Journal of Medicinal ChemistryISSN
0022-2623Publisher
American Chemical SocietyExternal DOI
Issue
15Volume
56Page range
6273-6277Department affiliated with
- Chemistry Publications
Full text available
- No
Peer reviewed?
- Yes
Legacy Posted Date
2016-01-15First Compliant Deposit (FCD) Date
2016-01-15Usage metrics
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