Structure–Activity Relationship for FDA Approved Drugs As Inhibitors of the Human Sodium Taurocholate Cotransporting Polypeptide (NTCP)

  • Zhongqi Dong, Sean Ekins, James E. Polli
  • Molecular Pharmaceutics, February 2013, American Chemical Society (ACS)
  • DOI: 10.1021/mp300453k

NTCP pharmacophore and bayesian models

What is it about?

The sodium taurocholate cotransporting polypeptide (NTCP) is a key bile acid transporter. We describe using a set of compounds to develop a pharmacophore which is used to identify additional FDA approved drugs as inhibitors. A bigger dataset is created and used to build a Bayesian model. This inturn is tested with additional drugs. We compared ASBT and NTCP activity and suggested the former is more permissive.

Why is it important?

A combination of computational and in vitro approaches was used to discover new NTCP inhibitors across many different therapeutic classes. This study showed that small datasets can be used to enlarge the number of inhibitors discovered.

Perspectives

Dr Sean Ekins
Collaborations in Chemistry

This study was important for showing the relative promiscuity of ASBT compared to NTCP inhibitors. We rationaiized this on the basis of the number of pharmacophore features in each model.

Read Publication

http://dx.doi.org/10.1021/mp300453k

The following have contributed to this page: Dr Sean Ekins