A substrate pharmacophore for the human sodium taurocholate co-transporting polypeptide

  • Zhongqi Dong, Sean Ekins, James E. Polli
  • International Journal of Pharmaceutics, January 2015, Elsevier
  • DOI: 10.1016/j.ijpharm.2014.11.022

NTCP Substrate pharmacophore

What is it about?

We developed a common feature pharmacophore for human NTCP from 18 native bile acids and 2 bile acid conjugates. This was used to show FDA approved drugs could map to it. The modeling was combined with experimental work to show in vitro transport for Irbesartan and Losartan.

Why is it important?

NTCP is a target for hepatitis B virus entry, inhibition can prevent infection. In this study we focused on deriving a substrate pharmacophore. This was demonstrated to reliably predict FDA drugs that could map to it and were substrates in vitro. This could be used for selecting compounds with improved uptake by targeting this transporter.

Perspectives

Dr Sean Ekins
Collaborations in Chemistry

A useful example of how a small training set can be put to use for prediction and model validation. This provides a foundation for future model development and efforts to understand the SAR of NTCP.

Read Publication

http://dx.doi.org/10.1016/j.ijpharm.2014.11.022

The following have contributed to this page: Dr Sean Ekins