Structure-Activity Investigations and Optimisations of Non-metabolite Agonists for the Succinate Receptor 1

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Structure-Activity Investigations and Optimisations of Non-metabolite Agonists for the Succinate Receptor 1. / Rexen Ulven, Elisabeth; Trauelsen, Mette; Brvar, Matjaz; Lückmann, Michael; Bielefeldt, Line Ø; Jensen, Lisa K I; Schwartz, Thue W; Frimurer, Thomas M.

In: Scientific Reports, Vol. 8, No. 1, 10010, 2018, p. 1-18.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Rexen Ulven, E, Trauelsen, M, Brvar, M, Lückmann, M, Bielefeldt, LØ, Jensen, LKI, Schwartz, TW & Frimurer, TM 2018, 'Structure-Activity Investigations and Optimisations of Non-metabolite Agonists for the Succinate Receptor 1', Scientific Reports, vol. 8, no. 1, 10010, pp. 1-18. https://doi.org/10.1038/s41598-018-28263-7

APA

Rexen Ulven, E., Trauelsen, M., Brvar, M., Lückmann, M., Bielefeldt, L. Ø., Jensen, L. K. I., ... Frimurer, T. M. (2018). Structure-Activity Investigations and Optimisations of Non-metabolite Agonists for the Succinate Receptor 1. Scientific Reports, 8(1), 1-18. [10010]. https://doi.org/10.1038/s41598-018-28263-7

Vancouver

Rexen Ulven E, Trauelsen M, Brvar M, Lückmann M, Bielefeldt LØ, Jensen LKI et al. Structure-Activity Investigations and Optimisations of Non-metabolite Agonists for the Succinate Receptor 1. Scientific Reports. 2018;8(1):1-18. 10010. https://doi.org/10.1038/s41598-018-28263-7

Author

Rexen Ulven, Elisabeth ; Trauelsen, Mette ; Brvar, Matjaz ; Lückmann, Michael ; Bielefeldt, Line Ø ; Jensen, Lisa K I ; Schwartz, Thue W ; Frimurer, Thomas M. / Structure-Activity Investigations and Optimisations of Non-metabolite Agonists for the Succinate Receptor 1. In: Scientific Reports. 2018 ; Vol. 8, No. 1. pp. 1-18.

Bibtex

@article{88cbef969b2c43f79380581bffc56807,
title = "Structure-Activity Investigations and Optimisations of Non-metabolite Agonists for the Succinate Receptor 1",
abstract = "The succinate receptor 1 (SUCNR1) is a receptor for the metabolite succinate, which functions as a metabolic stress signal in the liver, kidney, adipose tissue and the retina. However, potent non-metabolite tool compounds are needed to reveal the physiological role and pharmacological potential of SUCNR1. Recently, we published the discovery of a computationally receptor-structure derived non-metabolite SUCNR1 agonist series with high target selectivity. We here report our structure-activity exploration and optimisation that has resulted in the development of agonists with nanomolar potency and excellent solubility and stability properties in a number of in vitro assays. Ligand-guided receptor models with high discriminative power between binding of active and inactive compounds were developed for design of novel chemotypes.",
author = "{Rexen Ulven}, Elisabeth and Mette Trauelsen and Matjaz Brvar and Michael L{\"u}ckmann and Bielefeldt, {Line {\O}} and Jensen, {Lisa K I} and Schwartz, {Thue W} and Frimurer, {Thomas M.}",
year = "2018",
doi = "10.1038/s41598-018-28263-7",
language = "English",
volume = "8",
pages = "1--18",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "nature publishing group",
number = "1",

}

RIS

TY - JOUR

T1 - Structure-Activity Investigations and Optimisations of Non-metabolite Agonists for the Succinate Receptor 1

AU - Rexen Ulven, Elisabeth

AU - Trauelsen, Mette

AU - Brvar, Matjaz

AU - Lückmann, Michael

AU - Bielefeldt, Line Ø

AU - Jensen, Lisa K I

AU - Schwartz, Thue W

AU - Frimurer, Thomas M.

PY - 2018

Y1 - 2018

N2 - The succinate receptor 1 (SUCNR1) is a receptor for the metabolite succinate, which functions as a metabolic stress signal in the liver, kidney, adipose tissue and the retina. However, potent non-metabolite tool compounds are needed to reveal the physiological role and pharmacological potential of SUCNR1. Recently, we published the discovery of a computationally receptor-structure derived non-metabolite SUCNR1 agonist series with high target selectivity. We here report our structure-activity exploration and optimisation that has resulted in the development of agonists with nanomolar potency and excellent solubility and stability properties in a number of in vitro assays. Ligand-guided receptor models with high discriminative power between binding of active and inactive compounds were developed for design of novel chemotypes.

AB - The succinate receptor 1 (SUCNR1) is a receptor for the metabolite succinate, which functions as a metabolic stress signal in the liver, kidney, adipose tissue and the retina. However, potent non-metabolite tool compounds are needed to reveal the physiological role and pharmacological potential of SUCNR1. Recently, we published the discovery of a computationally receptor-structure derived non-metabolite SUCNR1 agonist series with high target selectivity. We here report our structure-activity exploration and optimisation that has resulted in the development of agonists with nanomolar potency and excellent solubility and stability properties in a number of in vitro assays. Ligand-guided receptor models with high discriminative power between binding of active and inactive compounds were developed for design of novel chemotypes.

U2 - 10.1038/s41598-018-28263-7

DO - 10.1038/s41598-018-28263-7

M3 - Journal article

C2 - 29968758

VL - 8

SP - 1

EP - 18

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 10010

ER -

ID: 211856788