Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT08JVB)

• DTT Name: G-protein coupled receptor 120 (GPR120)
• Synonyms: PGR4; Omega3 fatty acid receptor 1; Omega-3 fatty acid receptor 1; O3FAR1; Gprotein coupled receptor PGR4; Gprotein coupled receptor GT01; Gprotein coupled receptor 129; GPR129; G-protein coupled receptor PGR4; G-protein coupled receptor GT01; G-protein coupled receptor 129; Free fatty acid receptor 4
• Gene Name: FFAR4
• DTT Type: Literature-reported target; [1]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: FFAR4_HUMAN
• TTD ID: T51385
• Sequence:
  MSPECARAAGDAPLRSLEQANRTRFPFFSDVKGDHRLVLAAVETTVLVLIFAVSLLGNVC
  ALVLVARRRRRGATACLVLNLFCADLLFISAIPLVLAVRWTEAWLLGPVACHLLFYVMTL
  SGSVTILTLAAVSLERMVCIVHLQRGVRGPGRRARAVLLALIWGYSAVAALPLCVFFRVV
  PQRLPGADQEISICTLIWPTIPGEISWDVSFVTLNFLVPGLVIVISYSKILQITKASRKR
  LTVSLAYSESHQIRVSQQDFRLFRTLFLLMVSFFIMWSPIIITILLILIQNFKQDLVIWP
  SLFFWVVAFTFANSALNPILYNMTLCRNEWKKIFCCFWFPEKGAILTDTSVKRNDLSIIS
  G
• Function: Signals via a G(q)/G(11)-coupled pathway. Acts as a receptor for omega-3 fatty acids and mediates robust anti-inflammatory effects, particularly in macrophages and fat cells. The anti-inflammatory effects involve inhibition of TAK1 through a beta-arrestin 2 (ARRB2)/TAB1-dependent effect, but independent of the G(q)/G(11)-coupled pathway. Mediates potent insulin sensitizing and antidiabetic effects by repressing macrophage-induced tissue inflammation. May mediate the taste of fatty acids. Mediates FFA-induced inhibition of apoptosis in enteroendocrine cells. May play a role in the regulation of adipocyte development and differentiation. Receptor for medium and long-chain free fatty acids (FFAs).
• Reactome Pathway:
  G alpha (q) signalling events (R-HSA-416476)
  Free fatty acid receptors (R-HSA-444209)
  Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) (R-HSA-381771)

Molecular Interaction Atlas (MIA) of This DTT

6 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
alpha-linolenic acid	DMY64HE	Discovery agent	N.A.	Investigative	[2]
grifolic acid	DMGTRZE	Discovery agent	N.A.	Investigative	[3]
GW9508	DMVKZ5I	Discovery agent	N.A.	Investigative	[4]
NCG21	DMMRWJG	Discovery agent	N.A.	Investigative	[5]
PMID24997608CA	DML0PFU	Discovery agent	N.A.	Investigative	[6]
TUG-891	DMJRGZT	Discovery agent	N.A.	Investigative	[7]

References

• [1] PPAR ligands and their therapeutic applications: a patent review (2008 - 2014).Expert Opin Ther Pat. 2015 Feb;25(2):175-91.
• [2] Cloning and characterization of the rat free fatty acid receptor GPR120: in vivo effect of the natural ligand on GLP-1 secretion and proliferation of pancreatic beta cells. Naunyn Schmiedebergs Arch Pharmacol. 2008 Jun;377(4-6):515-22.
• [3] Novel selective ligands for free fatty acid receptors GPR120 and GPR40. Naunyn Schmiedebergs Arch Pharmacol. 2009 Sep;380(3):247-55.
• [4] Free fatty acid receptors and drug discovery. Biol Pharm Bull. 2008 Oct;31(10):1847-51.
• [5] Identification of G protein-coupled receptor 120-selective agonists derived from PPARgamma agonists. J Med Chem. 2008 Dec 11;51(23):7640-4.
• [6] A Gpr120-selective agonist improves insulin resistance and chronic inflammation in obese mice. Nat Med. 2014 Aug;20(8):942-7.
• [7] Discovery of a potent and selective GPR120 agonist. J Med Chem. 2012 May 10;55(9):4511-5.