First nondiscriminating translocator protein ligands produced from a carbazole scaffold

Hei Wun Alison Cheng; Renee Sokias; Eryn L. Werry; Lars M. Ittner; Tristan A. Reekie; Jonathan Du; Quanqing Gao; David E. Hibbs; Michael Kassiou

doi:10.1021/acs.jmedchem.9b00980

First nondiscriminating translocator protein ligands produced from a carbazole scaffold

Hei Wun Alison Cheng, Renee Sokias, Eryn L. Werry, Lars M. Ittner, Tristan A. Reekie, Jonathan Du, Quanqing Gao, David E. Hibbs, Michael Kassiou^*

^*Corresponding author for this work

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

15 Citations (Scopus)

Abstract

Development of neuroinflammation agents targeting the translocator protein (TSPO) has been hindered by a common single nucleotide polymorphism (A147T) at which TSPO ligands commonly lose affinity. To this end, carbazole acetamide scaffolds were synthesized and structure activity relationships elaborated to explore the requirements for high-affinity binding to both TSPO wild type (WT) and the polymorphic TSPO A147T. This study reports high binding affinity and nondiscriminating TSPO ligands.

Original language	English
Pages (from-to)	8235-8248
Number of pages	14
Journal	Journal of Medicinal Chemistry
Volume	62
Issue number	17
DOIs	https://doi.org/10.1021/acs.jmedchem.9b00980
Publication status	Published - 12 Sept 2019

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title = "First nondiscriminating translocator protein ligands produced from a carbazole scaffold",

abstract = "Development of neuroinflammation agents targeting the translocator protein (TSPO) has been hindered by a common single nucleotide polymorphism (A147T) at which TSPO ligands commonly lose affinity. To this end, carbazole acetamide scaffolds were synthesized and structure activity relationships elaborated to explore the requirements for high-affinity binding to both TSPO wild type (WT) and the polymorphic TSPO A147T. This study reports high binding affinity and nondiscriminating TSPO ligands.",

author = "Cheng, {Hei Wun Alison} and Renee Sokias and Werry, {Eryn L.} and Ittner, {Lars M.} and Reekie, {Tristan A.} and Jonathan Du and Quanqing Gao and Hibbs, {David E.} and Michael Kassiou",

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doi = "10.1021/acs.jmedchem.9b00980",

language = "English",

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T1 - First nondiscriminating translocator protein ligands produced from a carbazole scaffold

AU - Cheng, Hei Wun Alison

AU - Sokias, Renee

AU - Werry, Eryn L.

AU - Ittner, Lars M.

AU - Reekie, Tristan A.

AU - Du, Jonathan

AU - Gao, Quanqing

AU - Hibbs, David E.

AU - Kassiou, Michael

PY - 2019/9/12

Y1 - 2019/9/12

N2 - Development of neuroinflammation agents targeting the translocator protein (TSPO) has been hindered by a common single nucleotide polymorphism (A147T) at which TSPO ligands commonly lose affinity. To this end, carbazole acetamide scaffolds were synthesized and structure activity relationships elaborated to explore the requirements for high-affinity binding to both TSPO wild type (WT) and the polymorphic TSPO A147T. This study reports high binding affinity and nondiscriminating TSPO ligands.

AB - Development of neuroinflammation agents targeting the translocator protein (TSPO) has been hindered by a common single nucleotide polymorphism (A147T) at which TSPO ligands commonly lose affinity. To this end, carbazole acetamide scaffolds were synthesized and structure activity relationships elaborated to explore the requirements for high-affinity binding to both TSPO wild type (WT) and the polymorphic TSPO A147T. This study reports high binding affinity and nondiscriminating TSPO ligands.

UR - http://www.scopus.com/inward/record.url?scp=85072133504&partnerID=8YFLogxK

U2 - 10.1021/acs.jmedchem.9b00980

DO - 10.1021/acs.jmedchem.9b00980

M3 - Article

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AN - SCOPUS:85072133504

SN - 0022-2623

VL - 62

SP - 8235

EP - 8248

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 17

ER -

First nondiscriminating translocator protein ligands produced from a carbazole scaffold

Abstract

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