Re-engineering of the Duocarmycin Structural Architecture Enables Bioprecursor Development Targeting CYP1A1 and CYP2W1 for Biological Activity
详细信息 查看全文
- 作者：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
- 刊名：Journal of Medicinal Chemistry
- 出版年：2013
- 出版时间：August 8, 2013
- 年：2013
- 卷：56
- 期：15
- 页码：6273-6277
- 全文大小：290K
- 年卷期：v.56,no.15(August 8, 2013)
- ISSN：1520-4804
文摘
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鈥搉M 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.