AH-7614

Names

[ Name ]:
AH-7614

[Synonym ]:
4-methyl-N-9H-xanthen-9-yl-Benzamide
N-xanthen-9-yl-p-toluamide
N-xanthen-9-yl-toluene-4-sulfonamide
N-xanthyl-p-toluenesulfonamide

Biological Activity

[Description]:

AH-7614 is a potent and selective FFA4 antagonist, with pIC50s of 7.1, 8.1, and 8.1 for human, mouse, and rat FFA4, respectively. AH-7614 has selectivity for FFA4 over FFA1 (pIC50<4.6). AH-7614 is also a negative allosteric modulator (NAM) of FFA4. AH-7614 is able to block effects of both the polyunsaturated ω-6 fatty acid linoleic acid and the synthetic FFA4 agonist[1][2].

[Related Catalog]:

Signaling Pathways >> GPCR/G Protein >> GPR120

Research Areas >> Metabolic Disease

[Target]

pIC50: 7.1 (human FFA4)[1]

[In Vitro]

AH-7614 (compound 39) (0.063-1 μM) blocks intracellular Ca2+ response induced by both linoleic acid and FFAR4 agonist in FFA4 expressing U2OS cells[1]. AH-7614 (100 μM) abolishes the enhancement in glucose-stimulated insulin secretion by GSK137647A in NCI-H716 cells[1]. AH-7614 (0.001-10 μM; 15 min) blocks TUG-891-mediated internalization of FFA4 from the cell surface (pIC50=7.70)[2]. AH-7614 (10 μM; 30 min) blocks agonist-induced elevation of intracellular inositol monophosphates and phosphorylation of FFA4[2].

[In Vivo]

AH7614 (50 μg; intratumoral injection once every 4 d for 20 d) reduces the tumor growth in mice[3]. AH7614 (50 μg; intratumoral injection one day prior to epirubicin injection) enhances cancer cell sensitivity to the chemotherapy and inhibit tumor progression by blocking GPR120 signaling in combination with Epirubicin[3].

[References]

[1]. Sparks SM, et, al. Identification of diarylsulfonamides as agonists of the free fatty acid receptor 4 (FFA4/GPR120). Bioorg Med Chem Lett. 2014 Jul 15;24(14):3100-3.

[2]. Watterson KR, et, al. Probe-Dependent Negative Allosteric Modulators of the Long-Chain Free Fatty Acid Receptor FFA4. Mol Pharmacol. 2017 Jun;91(6):630-641.

[3]. Wang X, et, al. Fatty acid receptor GPR120 promotes breast cancer chemoresistance by upregulating ABC transporters expression and fatty acid synthesis. EBioMedicine. 2019 Feb;40:251-262.

Chemical & Physical Properties

[ Density]:
1.37g/cm3

[ Boiling Point ]:
505.9ºC at 760mmHg

[ Molecular Formula ]:
C₂₀H₁₇NO₃S

[ Molecular Weight ]:
351.41900

[ Flash Point ]:
259.8ºC

[ Exact Mass ]:
351.09300

[ PSA ]:
63.78000

[ LogP ]:
5.64030

[ Index of Refraction ]:
1.685

Safety Information

[ HS Code ]:
2935009090

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2935009090

[ Summary ]:
2935009090 other sulphonamides VAT:17.0% Tax rebate rate:9.0% Supervision conditions:none MFN tariff:6.5% General tariff:35.0%