Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 56, Issue 15, Pages 6273-6277Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jm4000209
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Funding
- EPSRC
- YCR [B207]
- Swedish Cancer Society
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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.
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