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

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

doi:10.1021/acs.jmedchem.5b01288

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

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

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

13 Citations (Scopus)

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.

Original language	English
Pages (from-to)	8743-8749
Number of pages	7
Journal	Journal of Medicinal Chemistry
Volume	58
Issue number	21
DOIs	https://doi.org/10.1021/acs.jmedchem.5b01288
Publication status	Published - 12 Nov 2015
Externally published	Yes

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10.1021/acs.jmedchem.5b01288

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Narlawar, R., Werry, E. L., Scarf, A. M., Hanani, R., Chua, S. W., King, V. A., Barron, M. L., Martins, R. N., Ittner, L. M., Rendina, L. M., & 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. https://doi.org/10.1021/acs.jmedchem.5b01288

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

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.",

author = "Rajeshwar Narlawar and Werry, {Eryn L.} and Scarf, {Alana M.} and Raphy Hanani and Chua, {Sook Wern} and King, {Victoria A.} and Barron, {Melissa L.} and Martins, {Ralph N.} and Ittner, {Lars M.} and Rendina, {Louis M.} and Michael Kassiou",

year = "2015",

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day = "12",

doi = "10.1021/acs.jmedchem.5b01288",

language = "English",

volume = "58",

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AU - Narlawar, Rajeshwar

AU - Werry, Eryn L.

AU - Scarf, Alana M.

AU - Hanani, Raphy

AU - Chua, Sook Wern

AU - King, Victoria A.

AU - Barron, Melissa L.

AU - Martins, Ralph N.

AU - Ittner, Lars M.

AU - Rendina, Louis M.

AU - Kassiou, Michael

PY - 2015/11/12

Y1 - 2015/11/12

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84947483855&partnerID=8YFLogxK

U2 - 10.1021/acs.jmedchem.5b01288

DO - 10.1021/acs.jmedchem.5b01288

M3 - Article

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AN - SCOPUS:84947483855

SN - 0022-2623

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EP - 8749

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 21

ER -

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

Abstract

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