Inhibition of Her2 Transcription by Small Organic Molecules
Abstract
Overexpression of the Her2 protein has been found in -30% of breast tumors, and the inhibition of Her2 expression may be an effective way to treat Her2-positive patients. I proposed high-throughput screen of chemical libraries to isolate small molecules that inhibit Her2 transcription by disrupting the interaction of two cancer-linked nuclear proteins, ESX and Sur-2(DRIP13O). The compound that we named adamanolol was discovered from a chemical library of 2,422 organic compounds that are all equipped with an indole- like electron-rich pharmacore. The drug-like compound selectively impaired the viability of Her2 positive breast cancer cell lines and reduced the expression of Her2 protein in Her2 positive SK-BR3 cells. In addition, adamanolol competed with FITC-labeled ESX( sub l29-145) for the interaction with Sur-2 in vitro. These results support hypothesis that Sur-2 is a chemically tractable protein that plays an important role in overexpressing Her2 in breast tumors and may serve as a pharmaceutical target for cancer therapy.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2003
- Accession Number
- ADA415950
Entities
People
- Motonari Uesugi
- Yongmun Choi
Organizations
- Baylor College of Medicine