First demonstration of positive allosteric-like modulation at the human wild type translocator protein (TSPO)

Authors

Rajeshwar Narlawar
Eryn L. Werry
Alana M. Scarf
Raphy Hanani
Sook Wern Chua
Victoria A. King
Melissa L. Barron
Ralph N. Martins, Edith Cowan UniversityFollow
Lars M. Ittner
Louis M. Rendina
Michael Kassiou

Document Type

Journal Article

Publication Title

Journal of Medicinal Chemistry

Publisher

American Chemical Society

School

School of Medical and Health Sciences

RAS ID

21495

Comments

Narlawar, R., Werry, E. L., Scarf, A. M., Hanani, R., Chua, S. W., King, V. A., ... Kassiou, M. (2015). First demonstration of positive allosteric-like modulation at the human wild type translocator protein (TSPO). Journal of Medicinal Chemistry, 58(21), 8743-8749. Available here

Abstract

We show that changing the number and position of nitrogen atoms in the heteroatomic core of a pyrazolopyrimidine acetamide is sufficient to induce complex binding to wild type human TSPO. Only compounds with this complex binding profile lacked intrinsic effect on glioblastoma proliferation but positively modulated the antiproliferative effects of a synthetic TSPO ligand. To the best of our knowledge this is the first demonstration of allosteric-like interaction at the wild type human TSPO.

DOI

10.1021/acs.jmedchem.5b01288

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