The novel chemical entity YTR107 inhibits recruitment of nucleophosmin to sites of DNA damage, suppressing repair of DNA double-strand breaks and enhancing radiosensitization.

ABSTRACT:

Purpose

Radiation therapy continues to be an important therapeutic strategy for providing definitive local/regional control of human cancer. However, oncogenes that harbor driver mutations and/or amplifications can compromise therapeutic efficacy. Thus, there is a need for novel approaches that enhance the DNA damage produced by ionizing radiation.

Experimental design

A forward chemical genetic approach coupled with cell-based phenotypic screening of several tumor cell lines was used to identify a novel chemical entity (NCE) that functioned as a radiation sensitizer. Proteomics, comet assays, confocal microscopy, and immunoblotting were used to identify the biological target.

Results

The screening process identified a 5-((N-benzyl-1H-indol-3-yl)-methylene)pyrimidine-2

SUBMITTER: Sekhar KR 

PROVIDER: S-EPMC3195947 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature