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GPR40 agonist 2

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Background Information of GPR40 agonist 2

GPR40 agonist 2 (Compound 10) is a novel GPR40 agonist with an EC50 of 2.87±0.73 μM. GPR40, also known as free fatty acid receptor 1 (FFAR1), is a member of G protein-coupled receptors (GPCR) family and has emerged as an attractive target for the treatment of type 2 diabetes mellitus.

Solubility of GPR40 agonist 2

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Mechanism and Indications

Signaling Pathways GPCR/G Protein
Target GPR40
Research Area Metabolic Disease
Indications

Clinical Information

Product Name Sponsor & Collaborators Indications Start Date End Date Phase

Chemical Information

M.Wt Formula CAS No. Synonyms
370.44 C25H22O3 Compound 10

Structure Information of GPR40 agonist 2

Smiles C(O)(=O)C#CC1=CC=C(OCC2C=CC=C(C3=C(C)C=C(C)C=C3C)C=2)C=C1
InChI InChI=1S/C25H22O3/c1-17-13-18(2)25(19(3)14-17)22-6-4-5-21(15-22)16-28-23-10-7-20(8-11-23)9-12-24(26)27/h4-8,10-11,13-15H,16H2,1-3H3,(H,26,27)

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AMG 837 (calcium hydrate) 1259389-38-2 C26H22F3O4- 9
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GPR40 Activator 1 1309435-60-6 C31H31NO3S 6
AMG 837 865231-46-5 C26H21F3O3 12
TUG-770 1402601-82-4 C19H14FNO2 13
GW9508 885101-89-3 C22H21NO3 22
TAK-875 1000413-72-8 C29H32O7S 16
GW-1100 306974-70-9 C27H25FN4O4S 9
GPR40 Activator 2 1312787-30-6 C28H29NO6S2 6
DC260126 346692-04-4 C32H31N5O 7
M-I C19H22O5S 0
T-1676427 1000414-39-0 C29H32O8S 0
JTT-851 C23H28O3 0
Astellas C27H30N4O4 0
MK-2305 905723-46-8 C19H13ClF3NO4S 0
Mochida 1469495-84-8 C30H35NO6S 0
BMS-986118 1610562-74-7 C25H28ClF3N4O4 2
AM-6226 C32H36F2O4 0
GPR40 agonist 1 1312788-44-5 C24H20O3 0
GPR40 agonist 3 C23H18O3 0

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Chemical and Physical Properties

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Reference

[1].Jiang XW, et al. Design, synthesis, and biological evaluations of phenylpropiolic acid derivatives as novel GPR40 agonists. Eur J Med Chem. 2018 Aug 31;158:123-133.
GPR40, also known as free fatty acid receptor 1 (FFAR1), is a member of G protein-coupled receptors (GPCR) family and has emerged as an attractive target for the treatment of type 2 diabetes mellitus. So far, most of the synthetic GPR40 agonists, including several drug candidates discontinued in clinical trials, were derived from the phenylpropionic acid scaffold. For discovering novel GPR40 agonists with diverse chemical structures, a series of phenylpropiolic acid derivatives were designed, synthesized, and evaluated under a battery of bioassays. Compound 9, the most potent compound in this series, exhibited submicromolar agonist activity and similar agonistic efficacy compared to that of TAK-875. In addition, compound 9 was able to dose-dependently amplify glucose-stimulated insulin secretion (GSIS) in pancreatic β-cell line MIN6, which could be reversed by a selective GPR40 antagonist GW1100. In addition, compound 9 was found to have potent glucose-lowering effects during an oral glucose tolerance test in normal C57BL/6 mice.

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