Discovery of a Potent Free Fatty Acid 1 Receptor Agonist with Low Lipophilicity, Low Polar Surface Area and Robust in Vivo Efficacy

Steffen Vissing Fahnøe Hansen; Elisabeth Christiansen; Christian Urban; Brian D Hudson; Claire J Stocker; Maria E Due-Hansen; Ed T Wargent; Bharat Shimpukade; Reinaldo Almeida; Christer S Ejsing; Michael A Cawthorne; Matthias U Kassack; Graeme Milligan; Trond Ulven

doi:10.1021/acs.jmedchem.5b01962

Discovery of a Potent Free Fatty Acid 1 Receptor Agonist with Low Lipophilicity, Low Polar Surface Area and Robust in Vivo Efficacy

Steffen Vissing Fahnøe Hansen, Elisabeth Christiansen, Christian Urban, Brian D Hudson, Claire J Stocker, Maria E Due-Hansen, Ed T Wargent, Bharat Shimpukade, Reinaldo Almeida, Christer S Ejsing, Michael A Cawthorne, Matthias U Kassack, Graeme Milligan, Trond Ulven

18 Citations (Scopus)

Abstract

The free fatty acid receptor 1 (FFA1 or GPR40) is established as an interesting potential target for treatment of type 2 diabetes. However, to obtain optimal ligands, it may be necessary to limit both lipophilicity and polar surface area, translating to a need for small compounds. We here describe the identification of 24, a potent FFA1 agonist with low lipophilicity and very high ligand efficiency that exhibit robust glucose lowering effect.

Original language	English
Journal	Journal of Medicinal Chemistry
Volume	59
Issue number	6
Pages (from-to)	2841-2846
Number of pages	6
ISSN	0022-2623
DOIs	https://doi.org/10.1021/acs.jmedchem.5b01962
Publication status	Published - 24 Mar 2016
Externally published	Yes

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Hansen, S. V. F., Christiansen, E., Urban, C., Hudson, B. D., Stocker, C. J., Due-Hansen, M. E., Wargent, E. T., Shimpukade, B., Almeida, R., Ejsing, C. S., Cawthorne, M. A., Kassack, M. U., Milligan, G., & Ulven, T. (2016). Discovery of a Potent Free Fatty Acid 1 Receptor Agonist with Low Lipophilicity, Low Polar Surface Area and Robust in Vivo Efficacy. Journal of Medicinal Chemistry, 59(6), 2841-2846. https://doi.org/10.1021/acs.jmedchem.5b01962

Discovery of a Potent Free Fatty Acid 1 Receptor Agonist with Low Lipophilicity, Low Polar Surface Area and Robust in Vivo Efficacy. / Hansen, Steffen Vissing Fahnøe; Christiansen, Elisabeth; Urban, Christian et al.
In: Journal of Medicinal Chemistry, Vol. 59, No. 6, 24.03.2016, p. 2841-2846.

Research output: Contribution to journal › Journal article › Research › peer-review

Hansen, SVF, Christiansen, E, Urban, C, Hudson, BD, Stocker, CJ, Due-Hansen, ME, Wargent, ET, Shimpukade, B, Almeida, R, Ejsing, CS, Cawthorne, MA, Kassack, MU, Milligan, G & Ulven, T 2016, 'Discovery of a Potent Free Fatty Acid 1 Receptor Agonist with Low Lipophilicity, Low Polar Surface Area and Robust in Vivo Efficacy', Journal of Medicinal Chemistry, vol. 59, no. 6, pp. 2841-2846. https://doi.org/10.1021/acs.jmedchem.5b01962

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abstract = "The free fatty acid receptor 1 (FFA1 or GPR40) is established as an interesting potential target for treatment of type 2 diabetes. However, to obtain optimal ligands, it may be necessary to limit both lipophilicity and polar surface area, translating to a need for small compounds. We here describe the identification of 24, a potent FFA1 agonist with low lipophilicity and very high ligand efficiency that exhibit robust glucose lowering effect.",

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AU - Hansen, Steffen Vissing Fahnøe

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AU - Urban, Christian

AU - Hudson, Brian D

AU - Stocker, Claire J

AU - Due-Hansen, Maria E

AU - Wargent, Ed T

AU - Shimpukade, Bharat

AU - Almeida, Reinaldo

AU - Ejsing, Christer S

AU - Cawthorne, Michael A

AU - Kassack, Matthias U

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AB - The free fatty acid receptor 1 (FFA1 or GPR40) is established as an interesting potential target for treatment of type 2 diabetes. However, to obtain optimal ligands, it may be necessary to limit both lipophilicity and polar surface area, translating to a need for small compounds. We here describe the identification of 24, a potent FFA1 agonist with low lipophilicity and very high ligand efficiency that exhibit robust glucose lowering effect.

U2 - 10.1021/acs.jmedchem.5b01962

DO - 10.1021/acs.jmedchem.5b01962

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Discovery of a Potent Free Fatty Acid 1 Receptor Agonist with Low Lipophilicity, Low Polar Surface Area and Robust in Vivo Efficacy

Abstract

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