Translational Cell Signaling and Metabolism

A novel inhibitor of liver drug transporters

Recently, researchers in TSG found that Ncp-M1 blocks the liver-specific transporter proteins OATP1B1/OATP1B3. These transporters are responsible for hepatocellular uptake of growth-stimulating steroids, several drugs, and toxins like microcystin, and are an important part of the detoxification machinery of the liver. Ncp-M1 is non-toxic to both liver cells and other cell types, and its mechanism of action seems to be limited to transporter inhibition.

Lars Herfindal

Main content

We produced an analog of Ncp-M1 that preferentially inhibits transport via OATP1B3. OATP1B3 is normally expressed in liver, but becomes expressed in some aggressive common cancers as well (colon, mammary prostate carcinomas). OATP1B3 is believed to promote growth and protect against death by allowing the influx of trophic factors into cancer cells. We propose that Ncp-M1 derivatives may be useful to promote cancer cell death by blocking OATP1B3 with minimal interference with the crucial uptake system in the liver, since this consists also of OATP1B1. The article has just been published in Molecular Pharmaceutics http://pubs.acs.org/doi/full/10.1021/mp1002224.