Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT8WFXV)

• DTT Name: Hydroxycarboxylic acid receptor 3 (HCAR3)
• Synonyms: Nicotinic acid receptor 2; Niacin receptor 2; NIACR2; HM74B; HCA3; GPR109B; G-protein coupled receptor HM74B; G-protein coupled receptor HM74; G-protein coupled receptor 109B
• Gene Name: HCAR3
• DTT Type: Clinical trial target; [1]
• UniProt ID: HCAR3_HUMAN
• TTD ID: T00890
• Sequence:
  MNRHHLQDHFLEIDKKNCCVFRDDFIAKVLPPVLGLEFIFGLLGNGLALWIFCFHLKSWK
  SSRIFLFNLAVADFLLIICLPFVMDYYVRRSDWKFGDIPCRLVLFMFAMNRQGSIIFLTV
  VAVDRYFRVVHPHHALNKISNWTAAIISCLLWGITVGLTVHLLKKKLLIQNGTANVCISF
  SICHTFRWHEAMFLLEFFLPLGIILFCSARIIWSLRQRQMDRHAKIKRAITFIMVVAIVF
  VICFLPSVVVRIHIFWLLHTSGTQNCEVYRSVDLAFFITLSFTYMNSMLDPVVYYFSSPS
  FPNFFSTLINRCLQRKITGEPDNNRSTSVELTGDPNKTRGAPEALIANSGEPWSPSYLGP
  TSNNHSKKGHCHQEPASLEKQLGCCIE
• Function: Receptor for 3-OH-octanoid acid mediates a negative feedback regulation of adipocyte lipolysis to counteract prolipolytic influences under conditions of physiological or pathological increases in beta-oxidation rates. Acts as a low affinity receptor for nicotinic acid. This pharmacological effect requires nicotinic acid doses that are much higher than those provided by a normal diet.
• KEGG Pathway: cAMP signaling pathway (hsa04024)
• Reactome Pathway:
  G alpha (i) signalling events (R-HSA-418594)
  Hydroxycarboxylic acid-binding receptors (R-HSA-3296197)

Molecular Interaction Atlas (MIA) of This DTT

2 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ARI-3037MO	DM9LNXS	Cardiovascular disease	BA00-BE2Z	Phase 2	[1]
NIA-114	DM3ADQW	Plaque psoriasis	EA90.0	Clinical trial	[2]

9 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
2-hydroxyoctanoic acid	DMMILJS	Discovery agent	N.A.	Investigative	[3]
3-hydroxyoctanoic acid	DMS658R	Discovery agent	N.A.	Investigative	[3]
4-(n-propyl)amino-3-nitrobenzoic acid	DMP43HI	Discovery agent	N.A.	Investigative	[4]
5-methyl-5-(5-methylthiophen-3-yl)-4-oxo-4,5-dihydrofuran-2-carboxylic acid	DMO37W4	Discovery agent	N.A.	Investigative	[5]
D-kynurenine	DM0QZ6I	Discovery agent	N.A.	Investigative	[6]
D-tryptophan	DMKIML1	Discovery agent	N.A.	Investigative	[6]
IBC 293	DM8J24A	Discovery agent	N.A.	Investigative	[7]
PMID17358052C5b	DMR9TYV	Discovery agent	N.A.	Investigative	[5]
PMID19524438C6o	DMK5JB8	Discovery agent	N.A.	Investigative	[8]

References

• [1] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] Deorphanization of GPR109B as a receptor for the beta-oxidation intermediate 3-OH-octanoic acid and its role in the regulation of lipolysis. J Biol Chem. 2009 Aug 14;284(33):21928-33.
• [4] 3-Nitro-4-amino benzoic acids and 6-amino nicotinic acids are highly selective agonists of GPR109b. Bioorg Med Chem Lett. 2007 Dec 1;17(23):6619-22.
• [5] Analogues of acifran: agonists of the high and low affinity niacin receptors, GPR109a and GPR109b. J Med Chem. 2007 Apr 5;50(7):1445-8.
• [6] Aromatic D-amino acids act as chemoattractant factors for human leukocytes through a G protein-coupled receptor, GPR109B. Proc Natl Acad Sci U S A. 2009 Mar 10;106(10):3930-4.
• [7] 1-Alkyl-benzotriazole-5-carboxylic acids are highly selective agonists of the human orphan G-protein-coupled receptor GPR109b. J Med Chem. 2006 Feb 23;49(4):1227-30.
• [8] 5-N,N-Disubstituted 5-aminopyrazole-3-carboxylic acids are highly potent agonists of GPR109b. Bioorg Med Chem Lett. 2009 Aug 1;19(15):4207-9.