Choking breast cancer
doi:10.1038/nindia.2008.239 Published online 9 July 2008
A team of Indo-US researchers has zeroed in on a few novel compounds that inhibit the growth of human breast cancer cells. Using virtual screening techniques, the researchers have identified compounds which disrupt the activity of a particular receptor — a protein molecule — that sits on the cell membrane and induces unbridled growth of breast cancer cells1.
The growing resistance to anti-cancer drug tamoxifen spurred the researchers to devise a new strategy to overcome the flaws in the signaling mechanism of breast cancer cells. They found the human epidermal growth factor receptor-2 (HER-2) to be a promising target to develop anti-cancer drugs. (HER-2), a glycoprotein, plays a key role in breast cancer.
In search of molecules that could inhibit HER-2 activity, they used computer-based models and scoured a massive database of 35,000 compounds. The search was narrowed down to 57 compounds. Of these, 12 were found to be most effective. To test their efficacy, the researchers exposed a specific human breast cancer cell(SKBR3) that over express HER-2 to these twelve compounds.
The researchers found that the compounds blocked the binding of ATP (adenosine tri-phospahte) and subsequent transfer of phosphate group to the part of HER-2 that remains inside the cancer cells. This was found to inhibit the proliferation of the breast cancer cells.
The authors of this work are from: Department of Pharmacology and Pharmaceutical Sciences, University of Southern California; School of Pharmacy, Los Angeles, California; Division of Informatics, GVK Biosciences Pvt. Ltd., Technocrats Industrial Estate, Hyderabad, Andhra Pradesh, India.
- Gundla, R. et al. Discovery of Novel Small-Molecule Inhibitors of Human Epidermal Growth Factor Receptor-2: Combined Ligand and Target-Based Approach. J. Med. Chem. 51, 3367-3377 (2008) | Article |