A Substrate Pharmacophore for the Human Organic Cation/Carnitine Transporter Identifies Compounds Associated with Rhabdomyolysis

  • Sean Ekins, Lei Diao, James E. Polli
  • Molecular Pharmaceutics, February 2012, American Chemical Society (ACS)
  • DOI: 10.1021/mp200438v

hOCTN2 substrate pharmacophore

What is it about?

Initially a common features pharmacophore was generated with 9 substrates for the hOCTN2 transporter. The pharmacophore was used to identify other known substrates and search drug databases. The pharmacophore seemed to identify compounds with known incidence of rhabdomyolysis.

Why is it important?

This was the first substrate pharmacophore for this transporter developed. This work also suggested a link between hOCTN2 and rhabdomyolysis.

Perspectives

Dr Sean Ekins
Collaborations in Chemistry

This work showed the potential of using small transporter datasets to potentially identify other molecules that may interact with the same protein. The prospective testing of the model used literature data. The pharmacophore consisted of a positive ionizable feature and two hydrogen bond acceptors as well as excluded volume features. This model could be used for further prospective prediction of potential substrates

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http://dx.doi.org/10.1021/mp200438v

The following have contributed to this page: Dr Sean Ekins