1402601-82-4

Basic information

• Product Name: TUG-770
• Synonyms: TUG-770;4-[2-[2-(Cyanomethyl)phenyl]ethynyl]-2-fluorobenzenepropanoic acid;4-[2-[2-(Cyanomethyl)phenyl]ethynyl]-2-fluorobenzenepropanoic acid TUG-770;3-(4-((2-(Cyanomethyl)phenyl)ethynyl)-2-fluorophenyl)propanoic acid
• CAS NO: 1402601-82-4
• Molecular Formula: C₁₉H₁₄FNO₂
• Molecular Weight: 307.3183632
• EINECS: -0
• Mol File: 1402601-82-4.mol
• Article Data: 2

Chemical Properties

• Boiling Point: 523.5±50.0 °C(Predicted)
• Appearance: /
• Density: 1.28±0.1 g/cm3(Predicted)
• Solubility: insoluble in H2O; ≥11.85 mg/mL in DMSO; ≥9.5 mg/mL in EtOH with gentle warming and ultrasonic
• PKA: 4.61±0.10(Predicted)
• CAS DataBase Reference: TUG-770(CAS DataBase Reference)
• NIST Chemistry Reference: TUG-770(1402601-82-4)
• EPA Substance Registry System: TUG-770(1402601-82-4)

Safety Data

• Hazardous Substances Data: 1402601-82-4(Hazardous Substances Data)

Usage

Biological Activity

tug-770 is a potent free fatty acid receptor 1 (ffa1/gpr40) agonist. free fatty acid receptor 1 (ffa1 or gpr40) enhances the glucose-stimulated insulin secretion from pancreatic β-cells and attracts high interest as a new target for the treatment of type 2 diabetes.

in vitro

tug-770 showed a pronounced increase in potency on ffa1 with ec50 = 6 nm and 150-fold selectivity over ffa4. tug-770 showed a high selectivity over ffa2, ffa3, pparγ, and 54 diverse transporters, receptors, and enzymes. in the rat ins-1e cell line, tug-770 caused significantly increased insulin secretion at high glucose concentration and, as expected, no effect at low glucose concentration [1].

in vivo

pharmacokinetic studies of tug-770 in mice showed a fast oral absorption, higher plasma concentration, a longer half-life, lower clearance, and increased bioavailability. no adverse effects were seen in mice after four weeks of daily oral treatment of 20 mg/kg and acute treatment in doses up to 250 mg/kg. in vivo examination of tug-770 in an acute intraperitoneal glucose tolerance test in normal mice showed a good dose-dependent response with maximal reduction in glucose level reached at 50 mg/kg. the followed chronic oral glucose tolerance test study in dio mice showed that tug-770 was more effective than its analog. further evaluation of tug-770 in rats confirmed a significant glucose lowering effect for the high doses [1].

IC 50

6 nm

references

[1] christiansen e,hansen sv,urban c,hudson bd,wargent et,grundmann m,jenkins l,zaibi m,stocker cj,ullrich s,kostenis e,kassack mu,milligan g,cawthorne ma,ulven t. discovery of tug-770: a highly potent free fatty acid receptor 1 (ffa1/gpr40) agonist for treatment of type 2 diabetes. acs med chem lett.2013 may 9;4(5):441-445.

Upstream product

• 57848-46-1 4-bromo-2-fluorobenzaldehyde 
• 581778-88-3 (E)-ethyl 3-(4-bromo-2-fluorophenyl)acrylate 
• 1057674-14-2 ethyl 3-(4-bromo-2-fluorophenyl)propanoate 
• 1402601-93-7 methyl 3-(4-ethynyl-2-fluorophenyl)propanoate 
• 1402601-98-2 methyl 3-(4-((2-(cyanomethyl)phenyl)ethynyl)-2-fluorophenyl)propanoate 

Relevant articles and documents

Discovery of TUG-770: A highly potent free fatty acid receptor 1 (FFA1/GPR40) agonist for treatment of type 2 diabetes

Free fatty acid receptor 1 (FFA1 or GPR40) enhances glucose-stimulated insulin secretion from pancreatic β-cells and currently attracts high interest as a new target for the treatment of type 2 diabetes. We here report the discovery of a highly potent FFA1 agonist with favorable physicochemical and pharmacokinetic properties. The compound efficiently normalizes glucose tolerance in diet-induced obese mice, an effect that is fully sustained after 29 days of chronic dosing.