Modification of the duocarmycin pharmacophore enables CYP1A1 targeting for biological activity

Klaus Pors; Paul M Loadman; Steven D Shnyder; Mark Sutherland; Helen M Sheldrake; Meritxell Guino; Konstantinos Kiakos; John A Hartley; Mark Searcey; Laurence H Patterson

doi:10.1039/c1cc15638a

Modification of the duocarmycin pharmacophore enables CYP1A1 targeting for biological activity

Chem Commun (Camb). 2011 Nov 28;47(44):12062-4. doi: 10.1039/c1cc15638a. Epub 2011 Oct 14.

Authors

Klaus Pors¹, Paul M Loadman, Steven D Shnyder, Mark Sutherland, Helen M Sheldrake, Meritxell Guino, Konstantinos Kiakos, John A Hartley, Mark Searcey, Laurence H Patterson

Affiliation

¹ Institute of Cancer Therapeutics, University of Bradford, West Yorkshire BD7 1DP, UK.

PMID: 22002321
DOI: 10.1039/c1cc15638a

Abstract

The identification of an agent that is selectively activated by a cytochrome P450 (CYP) has the potential for tissue specific dose intensification as a means of significantly improving its therapeutic value. Towards this goal, we disclose evidence for the pathway of activation of a duocarmycin analogue, ICT2700, which targets CYP1A1 for biological activity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alkylating Agents / chemistry
Alkylating Agents / pharmacology*
Animals
Biotransformation
CHO Cells
Cricetinae
Cricetulus
Cytochrome P-450 CYP1A1 / genetics
Cytochrome P-450 CYP1A1 / metabolism*
Cytotoxins / chemistry
Cytotoxins / pharmacology*
Humans
Indoles / chemistry
Indoles / pharmacology*
Molecular Targeted Therapy
Oxidation-Reduction

Substances

Alkylating Agents
Cytotoxins
Indoles
Cytochrome P-450 CYP1A1

Abstract

Publication types

MeSH terms

Substances

Grants and funding