In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 8_Supplement ( 2012-04-15), p. 4741-4741
Abstract:
We developed a novel method for drug discovery using active compounds as pharmacodynamic biomarkers in triple-negative breast cancer cell lines. [Materials and Methods] Compounds that selectively inhibit proliferation of triple-negative breast cancer were screened in triple-negative breast cancer cell lines (MDA-MB231, MDA-MB468 and HCC-38) and control MCF7 and HeLa cell lines. A small molecule library was designed to seek structural diversity by chemical informatics and a total of 30,000 synthetic compounds were assessed considering drug similarities. The differences in gene expression profiles in the cell lines between before and after the addition of the selected compounds were analyzed and compared with the control cells. [Results] Seven compounds that exhibited inhibitory effects on the triple-negative breast cancer cell lines were found in the compound library. These compounds exhibited inhibitory activity with IC50-values ranging from 1.2 to 10.8 μM. The results of the microarray analysis indicated several pathways including the irinotecan pathway that changed specifically in the triple-negative breast cancer cell lines by the addition of the compounds.[Conclusion] A research strategy to screen a compound library with structural diversity and develop a drug discovery system using active compounds as pharmacodynamic biomarkers can be widely applied as a new approach for developing innovative personalized medicine. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4741. doi:1538-7445.AM2012-4741
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2012-4741
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2012
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
