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HCA2 receptor

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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 312

Nomenclature: HCA2 receptor

Family: Hydroxycarboxylic acid receptors

Contents:

Gene and Protein Information Click here for help
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 363 12q24.31 HCAR2 hydroxycarboxylic acid receptor 2
Mouse 7 360 5 F Hcar2 hydroxycarboxylic acid receptor 2
Rat 7 360 12q15 Hcar2 hydroxycarboxylic acid receptor 2
Previous and Unofficial Names Click here for help
GPR109A | G protein-coupled receptor 109A | G-protein coupled receptor HM74A | niacin receptor 1 | Niacr1 | Nic1 | Nicotinic acid receptor | PUMAG
Database Links Click here for help
Specialist databases
GPCRdb hcar2_human (Hs), hcar2_mouse (Mm), hcar2_rat (Rn)
Other databases
Alphafold Q8TDS4 (Hs), Q9EP66 (Mm), Q80Z39 (Rn)
ChEMBL Target CHEMBL3785 (Hs), CHEMBL4420 (Mm), CHEMBL4731 (Rn)
DrugBank Target Q8TDS4 (Hs)
Ensembl Gene ENSG00000182782 (Hs), ENSMUSG00000045502 (Mm), ENSRNOG00000026653 (Rn)
Entrez Gene 338442 (Hs), 80885 (Mm), 353250 (Rn)
Human Protein Atlas ENSG00000182782 (Hs)
KEGG Gene hsa:338442 (Hs), mmu:80885 (Mm), rno:353250 (Rn)
OMIM 609163 (Hs)
Pharos Q8TDS4 (Hs)
RefSeq Nucleotide NM_177551 (Hs), NM_030701 (Mm), NM_181476 (Rn)
RefSeq Protein NP_808219 (Hs), NP_109626 (Mm), NP_852141 (Rn)
UniProtKB Q8TDS4 (Hs), Q9EP66 (Mm), Q80Z39 (Rn)
Wikipedia HCAR2 (Hs)
Natural/Endogenous Ligands Click here for help
butyric acid
β-D-hydroxybutyric acid
Potency order of endogenous ligands (Human)
β-D-hydroxybutyric acid > butyric acid

Download all structure-activity data for this target as a CSV file go icon to follow link

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[3H]nicotinic acid Small molecule or natural product Ligand is labelled Ligand is radioactive Ligand has a PDB structure Hs Full agonist 7.0 – 7.3 pKd 27,33,37
⤷ pKd 7.0 – 7.3 (Kd 1x10-7 – 5.01x10-8 M) [27,33,37]
MK 6892 Small molecule or natural product Ligand has a PDB structure Hs Full agonist 8.4 pKi 24
⤷ pKi 8.4 (Ki 4x10-9 M) [24]
5-butyl-1H-pyrazole-3-carboxylic acid Small molecule or natural product Ligand has a PDB structure Rn Partial agonist 7.1 pKi 34
⤷ pKi 7.1 [34]
monomethyl fumarate Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Full agonist 6.7 pKi 35
⤷ pKi 6.7 (Ki 1.8x10-7 M) [35]
SCH 900271 Small molecule or natural product Hs Agonist 8.7 pEC50 16
⤷ pEC50 8.7 [16]
MK 6892 Small molecule or natural product Ligand has a PDB structure Hs Full agonist 7.8 pEC50 24
⤷ pEC50 7.8 (EC50 1.6x10-8 M) [24]
MK 1903 Small molecule or natural product Hs Full agonist 7.6 pEC50 4
⤷ pEC50 7.6 (EC50 2.75x10-8 M) [4]
GSK256073 Small molecule or natural product Ligand has a PDB structure Hs Agonist 7.5 pEC50 28
⤷ pEC50 7.5 [28]
compound 43 [PMID: 34781683] Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Agonist 7.4 pEC50 19
⤷ pEC50 7.4 (EC50 3.98x10-8 M) [19]
Compound 780A Small molecule or natural product Hs Agonist 7.4 pEC50 19
⤷ pEC50 7.4 (EC50 3.98x10-8 M) [19]
Description: Agonist activity at HCAR2, determined in a [35S]-GTP&gammagS binding assay
compound (+)17a [PMID: 20363624] Small molecule or natural product Hs Full agonist 7.3 pEC50 5
⤷ pEC50 7.3 (EC50 4.5x10-8 M) [5]
(+)-5-(5-bromothiophen-3-yl)-5-methyl-4-oxo-4,5-dihydro-furan-2-carboxylic acid Small molecule or natural product Hs Full agonist 7.3 pEC50 11,29
⤷ pEC50 7.3 [11,29]
Compound 245A Small molecule or natural product Hs Agonist 7.2 pEC50 19
⤷ pEC50 7.2 (EC50 6.3x10-8 M) [19]
Description: Agonist activity at HCAR2, determined in a [35S]-GTP&gammagS binding assay
nicotinic acid Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 6.0 – 7.2 pEC50 27,33,37
⤷ pEC50 6.0 – 7.2 (EC50 1x10-6 – 6.31x10-8 M) [27,33,37]
acifran Small molecule or natural product Click here for species-specific activity table Hs Full agonist 5.7 – 5.9 pEC50 11,14,29,37
⤷ pEC50 5.7 – 5.9 [11,14,29,37]
MK 0354 Small molecule or natural product Hs Partial agonist 5.8 pEC50 22
⤷ pEC50 5.8 (EC50 1.65x10-6 M) [22]
acipimox Small molecule or natural product Approved drug Hs Full agonist 5.2 – 5.6 pEC50 27,37
⤷ pEC50 5.2 – 5.6 (EC50 6.31x10-6 – 2.51x10-6 M) [27,37]
3-pyridine-acetic acid Small molecule or natural product Hs Full agonist 5.3 pEC50 37
⤷ pEC50 5.3 [37]
5-methyl nicotinic acid Small molecule or natural product Hs Full agonist 5.1 pEC50 37
⤷ pEC50 5.1 [37]
monomethyl fumarate Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Full agonist 5.0 pEC50 30
⤷ pEC50 5.0 (EC50 9.4x10-6 M) [30]
cinnamic acid Small molecule or natural product Ligand has a PDB structure Hs Full agonist 3.6 pEC50 18
⤷ pEC50 3.6 (EC50 2.4x10-4 M) [18]
para-coumaric acid Small molecule or natural product Ligand has a PDB structure Hs Full agonist 3.5 pEC50 18
⤷ pEC50 3.5 (EC50 3.1x10-4 M) [18]
β-D-hydroxybutyric acid Small molecule or natural product Ligand is endogenous in the given species Ligand has a PDB structure Mm Full agonist 3.5 pEC50 29
⤷ pEC50 3.5 [29]
β-D-hydroxybutyric acid Small molecule or natural product Ligand is endogenous in the given species Ligand has a PDB structure Hs Full agonist 3.1 pEC50 29
⤷ pEC50 3.1 [29]
butyric acid Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Immunopharmacology Ligand Hs Agonist 2.8 pEC50
⤷ pEC50 2.8
compound 21 [PMID: 21185185] Small molecule or natural product Hs Full agonist 7.9 pIC50 10
⤷ pIC50 7.9 (IC50 1.2x10-8 M) [10]
compound 2g [PMID: 19309152] Small molecule or natural product Hs Full agonist 7.9 pIC50 23
⤷ pIC50 7.9 (IC50 1.3x10-8 M) [23]
compound 1q [PMID: 18029181] Small molecule or natural product Hs Partial agonist 6.8 pIC50 25
⤷ pIC50 6.8 (IC50 1.4x10-7 M) [25]
compound 8f [PMID: 20615702] Small molecule or natural product Hs Full agonist 6.4 pIC50 9
⤷ pIC50 6.4 (IC50 3.9x10-7 M) [9]
Compound 4a [PMID: 17452318] Small molecule or natural product Hs Agonist 5.9 pIC50 20
⤷ pIC50 5.9 (IC50 1.3x10-6 M) [20]
Description: Inhibition of forskolin-stimulated cAMP production in CHO-K1 cells stably transfected with HCAR2.
View species-specific agonist tables
Agonist Comments
Nicotinic acid has equal affinity for rat and mouse homologs of the receptor, both in the 'cold' and tritiated form.
Antagonist Comments
Currently no antagonists are known for the HCA2 receptor.
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
compound 9n [PMID: 18752940] Small molecule or natural product Ligand has a PDB structure Hs Positive 6.8 pEC50 26
⤷ pEC50 6.8 (EC50 1.7x10-7 M) [26]
compound 42 [PMID: 22420767] Small molecule or natural product Hs Positive 5.6 pEC50 3
⤷ pEC50 5.6 (EC50 2.6x10-6 M) [3]
Immunopharmacology Comments
The HCA2 receptor has been identified as a molecular target of fumarate anti-inflammatory drugs in an inflammatory skin disease model [36]. Monomethyl fumarate/dimethyl fumarate-induced activation of HCA2 is reported to inhibit the infiltration of neutrophils and monocytes into the skin which limits skin pathology. This effect is not observed in Hca2-null mice. The HCA2 receptor may also be implicated in mediating neuropathic pain/neuroinflammation, based on evidence that tactile allodynia in an animal model is Hca2-dependent [6]
Cell Type Associations
Immuno Cell Type:  Macrophages & monocytes
Cell Ontology Term:   monocyte (CL:0000576)
Comment:  Expressed in mouse monocytes.
References:  36
Immuno Cell Type:  Granulocytes
Cell Ontology Term:   neutrophil (CL:0000775)
Comment:  Expressed in mouse neutrophils.
References:  36
Immuno Process Associations
Immuno Process:  Immune regulation
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gi/Go family Adenylyl cyclase inhibition
Phospholipase A2 stimulation
Comments:  HCA2 is also shown to activate the MAPK cascade (ERK1/ERK2).
References:  20,31,33,37
Tissue Distribution Click here for help
Intestinal epithelial cells.
Species:  Human
Technique:  Immunohistochemistry.
References:  32
Adipose tissue.
Species:  Human
Technique:  Northern blotting.
References:  27,33,37
Keratinocytes.
Species:  Human
Technique:  RT-PCR.
References:  30
Adipose tissue.
Species:  Human
Technique:  RT-PCR.
References:  27,33,37
Neutrophils, Langerhans cells.
Species:  Human
Technique:  RT-PCR.
References:  13
Adipose tissue.
Species:  Mouse
Technique:  Northern blotting.
References:  27,33,37
Keratinocytes.
Species:  Mouse
Technique:  RT-PCR, genetic reporter mouse.
References:  8
Spleen, macrophages.
Species:  Mouse
Technique:  Northern blotting.
References:  21
Adipose tissue.
Species:  Mouse
Technique:  RT-PCR.
References:  27,33,37
Intestinal epithelial cells.
Species:  Mouse
Technique:  Immunohistochemistry.
References:  32
Retinal pigment epithelial cells.
Species:  Mouse
Technique:  Immunocytochemistry, RT-PCR.
References:  15
Expression Datasets Click here for help

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays Click here for help
Measurement of cAMP accumulation in HEK293 cells transfected with the mouse HCA2 receptor.
Species:  Mouse
Tissue:  HEK 293 cells.
Response measured:  Inhibition of forskolin-stimulated cAMP accumulation.
References:  27
Measurement of arachidonic acid release in human epidermoid A431 cells endogenously expressing the HCA2 receptor.
Species:  Human
Tissue:  A431 cells.
Response measured:  Enhancement of arachidonic acid release.
References:  31
Measurement of ERK1/2 phosphorylation in CHO cells transfected with the mouse HCA2 receptor.
Species:  Mouse
Tissue:  CHO cells.
Response measured:  Stimulation of ERK1/2 phosphorylation.
References:  14,33
Measurement of prostaglandin D2 release in Langerhans cells endogenously expressing the HCA2 receptor.
Species:  Human
Tissue:  Epidermal Langerhans cells.
Response measured:  Increase in prostaglandin D2 release.
References:  13
Measurement of intracellular [Ca2+] in epidermal Langerhans cells endogenously expressing the HCA2 receptor.
Species:  Mouse
Tissue:  Epidermal Langerhans cells.
Response measured:  Transient increase in intracellular [Ca2+].
References:  2
Measurement of cAMP accumulation in CHO cells transfected with the mouse HCA2 receptor
Species:  Human
Tissue:  CHO cells.
Response measured:  Inhibition of forskolin-stimulated cAMP accumulation.
References:  33
Measurement of intracellular [Ca2+] in human epidermoid A431 cells endogenously expressing the HCA2 receptor.
Species:  Human
Tissue:  A431 cells.
Response measured:  Transient increase in intracellular [Ca2+].
References:  31
Measurement of cAMP accumulation in CHO cells transfected with the human HCA2 receptor.
Species:  Human
Tissue:  CHO cells.
Response measured:  Inhibition of forskolin-stimulated cAMP accumulation.
References:  33
Measurement of [35S]GTPγS incorporation in membranes from HEK 293 cells transfected with the human HCA2 receptor.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  Stimulation of [35S]GTPγS binding.
References:  37
Measurement of cAMP accumulation in HEK 293 cells transfected with the human HCA2 receptor.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  Inhibition of forskolin-stimulated cAMP accumulation.
References:  27
Measurement of [35S]GTPγS incorporation in membranes from HEK 293 cells transfected with the mouse HCA2 receptor.
Species:  Mouse
Tissue:  HEK 293 cells.
Response measured:  Stimulation of [35S]GTPγS binding.
References:  37
Physiological Functions Click here for help
Inhibition of lipolytic activity.
Species:  Mouse
Tissue:  Adipocytes.
References:  33,38
Increase in dermal blood flow.
Species:  Mouse
Tissue:  Skin.
References:  2
Increase in ear blood flow.
Species:  Rat
Tissue:  Skin.
References:  7
HCA2 mediates nicotinic acid-induced flushing.
Species:  Mouse
Tissue: 
References:  1-2,7-8
HCA2 mediates the antilipolytic and anti-atherogenic effects of nicotinic acid.
Species:  Mouse
Tissue: 
References:  12,33
HCA2 mediates nicotinic acid-induced flushing.
Species:  Rat
Tissue: 
References:  1-2,7-8
HCA2 mediates brain neuroprotection.
Species:  Mouse
Tissue:  Macrophages, Ly-6C(Lo) monocytes.
References:  17
Physiological Consequences of Altering Gene Expression Click here for help
HCA2 receptor knockout mice do not flush in response to nicotinic acid.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  2
HCA2 receptor knockout mice do not respond with a decrease in plasma free fatty acid and triglyceride levels to nicotinic acid.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  33
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Niacr1tm1Soff Niacr1tm1Soff/Niacr1tm1Soff
involves: 129P2/OlaHsd * C57BL/6		 MGI:1933383  MP:0002118 abnormal lipid homeostasis PMID: 12563315 

References

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1. Benyó Z, Gille A, Bennett CL, Clausen BE, Offermanns S. (2006) Nicotinic acid-induced flushing is mediated by activation of epidermal langerhans cells. Mol Pharmacol, 70 (6): 1844-9. [PMID:17008386]

2. Benyó Z, Gille A, Kero J, Csiky M, Suchánková MC, Nüsing RM, Moers A, Pfeffer K, Offermanns S. (2005) GPR109A (PUMA-G/HM74A) mediates nicotinic acid-induced flushing. J Clin Invest, 115 (12): 3634-40. [PMID:16322797]

3. Blad CC, van Veldhoven JP, Klopman C, Wolfram DR, Brussee J, Lane JR, Ijzerman AP. (2012) Novel 3,6,7-substituted pyrazolopyrimidines as positive allosteric modulators for the hydroxycarboxylic acid receptor 2 (GPR109A). J Med Chem, 55 (7): 3563-7. [PMID:22420767]

4. Boatman PD, Lauring B, Schrader TO, Kasem M, Johnson BR, Skinner P, Jung JK, Xu J, Cherrier MC, Webb PJ et al.. (2012) (1aR,5aR)1a,3,5,5a-Tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid (MK-1903): a potent GPR109a agonist that lowers free fatty acids in humans. J Med Chem, 55 (8): 3644-66. [PMID:22435740]

5. Boatman PD, Schrader TO, Kasem M, Johnson BR, Skinner PJ, Jung JK, Xu J, Cherrier MC, Webb PJ, Semple G et al.. (2010) Potent tricyclic pyrazole tetrazole agonists of the nicotinic acid receptor (GPR109a). Bioorg Med Chem Lett, 20 (9): 2797-800. [PMID:20363624]

6. Boccella S, Guida F, De Logu F, De Gregorio D, Mazzitelli M, Belardo C, Iannotta M, Serra N, Nassini R, de Novellis V et al.. (2019) Ketones and pain: unexplored role of hydroxyl carboxylic acid receptor type 2 in the pathophysiology of neuropathic pain. FASEB J, 33 (1): 1062-1073. [PMID:30085883]

7. Carballo-Jane E, Gerckens LS, Luell S, Parlapiano AS, Wolff M, Colletti SL, Tata JR, Taggart AK, Waters MG, Richman JG et al.. (2007) Comparison of rat and dog models of vasodilatation and lipolysis for the calculation of a therapeutic index for GPR109A agonists. J Pharmacol Toxicol Methods, 56 (3): 308-16. [PMID:17643322]

8. Hanson J, Gille A, Zwykiel S, Lukasova M, Clausen BE, Ahmed K, Tunaru S, Wirth A, Offermanns S. (2010) Nicotinic acid- and monomethyl fumarate-induced flushing involves GPR109A expressed by keratinocytes and COX-2-dependent prostanoid formation in mice. J Clin Invest, 120 (8): 2910-9. [PMID:20664170]

9. Imbriglio JE, Chang S, Liang R, Raghavan S, Schmidt D, Smenton A, Tria S, Schrader TO, Jung JK, Esser C et al.. (2010) GPR109a agonists. Part 2: pyrazole-acids as agonists of the human orphan G-protein coupled receptor GPR109a. Bioorg Med Chem Lett, 20 (15): 4472-4. [PMID:20615702]

10. Imbriglio JE, DiRocco D, Bodner R, Raghavan S, Chen W, Marley D, Esser C, Holt TG, Wolff MS, Taggart AK et al.. (2011) The discovery of high affinity agonists of GPR109a with reduced serum shift and improved ADME properties. Bioorg Med Chem Lett, 21 (9): 2721-4. [PMID:21185185]

11. Jung JK, Johnson BR, Duong T, Decaire M, Uy J, Gharbaoui T, Boatman PD, Sage CR, Chen R, Richman JG et al.. (2007) Analogues of acifran: agonists of the high and low affinity niacin receptors, GPR109a and GPR109b. J Med Chem, 50 (7): 1445-8. [PMID:17358052]

12. Lukasova M, Malaval C, Gille A, Kero J, Offermanns S. (2011) Nicotinic acid inhibits progression of atherosclerosis in mice through its receptor GPR109A expressed by immune cells. J Clin Invest, 121 (3): 1163-73. [PMID:21317532]

13. Maciejewski-Lenoir D, Richman JG, Hakak Y, Gaidarov I, Behan DP, Connolly DT. (2006) Langerhans cells release prostaglandin D2 in response to nicotinic acid. J Invest Dermatol, 126 (12): 2637-46. [PMID:17008871]

14. Mahboubi K, Witman-Jones T, Adamus JE, Letsinger JT, Whitehouse D, Moorman AR, Sawicki D, Bergenhem N, Ross SA. (2006) Triglyceride modulation by acifran analogs: activity towards the niacin high and low affinity G protein-coupled receptors HM74A and HM74. Biochem Biophys Res Commun, 340 (2): 482-90. [PMID:16389067]

15. Martin PM, Ananth S, Cresci G, Roon P, Smith S, Ganapathy V. (2009) Expression and localization of GPR109A (PUMA-G/HM74A) mRNA and protein in mammalian retinal pigment epithelium. Mol Vis, 15: 362-72. [PMID:19223991]

16. Palani A, Rao AU, Chen X, Huang X, Su J, Tang H, Huang Y, Qin J, Xiao D, Degrado S et al.. (2012) Discovery of SCH 900271, a Potent Nicotinic Acid Receptor Agonist for the Treatment of Dyslipidemia. ACS Med Chem Lett, 3 (1): 63-8. [PMID:24900372]

17. Rahman M, Muhammad S, Khan MA, Chen H, Ridder DA, Müller-Fielitz H, Pokorná B, Vollbrandt T, Stölting I, Nadrowitz R et al.. (2014) The β-hydroxybutyrate receptor HCA2 activates a neuroprotective subset of macrophages. Nat Commun, 5: 3944. [PMID:24845831]

18. Ren N, Kaplan R, Hernandez M, Cheng K, Jin L, Taggart AK, Zhu AY, Gan X, Wright SD, Cai TQ. (2009) Phenolic acids suppress adipocyte lipolysis via activation of the nicotinic acid receptor GPR109A (HM74a/PUMA-G). J Lipid Res, 50 (5): 908-14. [PMID:19136666]

19. Richardson JC, Higgins GA, Upton N, Massey P, Cunningham M, Wilson S, Holenz J, Taylor C, Lavrov A, Lin H, et al.. (2024) The hydroxycarboxylic acid receptor HCA2 is required for the protective effect of ketogenic diet in epilepsy. Pharmacology Research & Perspectives, In press.

20. Richman JG, Kanemitsu-Parks M, Gaidarov I, Cameron JS, Griffin P, Zheng H, Guerra NC, Cham L, Maciejewski-Lenoir D, Behan DP et al.. (2007) Nicotinic acid receptor agonists differentially activate downstream effectors. J Biol Chem, 282 (25): 18028-36. [PMID:17452318]

21. Schaub A, Fütterer A, Pfeffer K. (2001) PUMA-G, an IFN-gamma-inducible gene in macrophages is a novel member of the seven transmembrane spanning receptor superfamily. Eur J Immunol, 31 (12): 3714-25. [PMID:11745392]

22. Semple G, Skinner PJ, Gharbaoui T, Shin YJ, Jung JK, Cherrier MC, Webb PJ, Tamura SY, Boatman PD, Sage CR et al.. (2008) 3-(1H-tetrazol-5-yl)-1,4,5,6-tetrahydro-cyclopentapyrazole (MK-0354): a partial agonist of the nicotinic acid receptor, G-protein coupled receptor 109a, with antilipolytic but no vasodilatory activity in mice. J Med Chem, 51 (16): 5101-8. [PMID:18665582]

23. Shen HC, Ding FX, Deng Q, Wilsie LC, Krsmanovic ML, Taggart AK, Carballo-Jane E, Ren N, Cai TQ, Wu TJ et al.. (2009) Discovery of novel tricyclic full agonists for the G-protein-coupled niacin receptor 109A with minimized flushing in rats. J Med Chem, 52 (8): 2587-602. [PMID:19309152]

24. Shen HC, Ding FX, Raghavan S, Deng Q, Luell S, Forrest MJ, Carballo-Jane E, Wilsie LC, Krsmanovic ML, Taggart AK et al.. (2010) Discovery of a biaryl cyclohexene carboxylic acid (MK-6892): a potent and selective high affinity niacin receptor full agonist with reduced flushing profiles in animals as a preclinical candidate. J Med Chem, 53 (6): 2666-70. [PMID:20184326]

25. Shen HC, Szymonifka MJ, Kharbanda D, Deng Q, Carballo-Jane E, Wu KK, Wu TJ, Cheng K, Ren N, Cai TQ et al.. (2007) Discovery of orally bioavailable and novel urea agonists of the high affinity niacin receptor GPR109A. Bioorg Med Chem Lett, 17 (24): 6723-8. [PMID:18029181]

26. Shen HC, Taggart AK, Wilsie LC, Waters MG, Hammond ML, Tata JR, Colletti SL. (2008) Discovery of pyrazolopyrimidines as the first class of allosteric agonists for the high affinity nicotinic acid receptor GPR109A. Bioorg Med Chem Lett, 18 (18): 4948-51. [PMID:18752940]

27. Soga T, Kamohara M, Takasaki J, Matsumoto S, Saito T, Ohishi T, Hiyama H, Matsuo A, Matsushime H, Furuichi K. (2003) Molecular identification of nicotinic acid receptor. Biochem Biophys Res Commun, 303 (1): 364-9. [PMID:12646212]

28. Sprecher D, Maxwell M, Goodman J, White B, Tang CM, Boullay V, de Gouville AC. (2015) Discovery and characterization of GSK256073, a non-flushing hydroxy-carboxylic acid receptor 2 (HCA2) agonist. Eur J Pharmacol, 756: 1-7. [PMID:25773497]

29. Taggart AK, Kero J, Gan X, Cai TQ, Cheng K, Ippolito M, Ren N, Kaplan R, Wu K, Wu TJ et al.. (2005) (D)-beta-Hydroxybutyrate inhibits adipocyte lipolysis via the nicotinic acid receptor PUMA-G. J Biol Chem, 280 (29): 26649-52. [PMID:15929991]

30. Tang H, Lu JY, Zheng X, Yang Y, Reagan JD. (2008) The psoriasis drug monomethylfumarate is a potent nicotinic acid receptor agonist. Biochem Biophys Res Commun, 375 (4): 562-5. [PMID:18722346]

31. Tang Y, Zhou L, Gunnet JW, Wines PG, Cryan EV, Demarest KT. (2006) Enhancement of arachidonic acid signaling pathway by nicotinic acid receptor HM74A. Biochem Biophys Res Commun, 345 (1): 29-37. [PMID:16674924]

32. Thangaraju M, Cresci GA, Liu K, Ananth S, Gnanaprakasam JP, Browning DD, Mellinger JD, Smith SB, Digby GJ, Lambert NA et al.. (2009) GPR109A is a G-protein-coupled receptor for the bacterial fermentation product butyrate and functions as a tumor suppressor in colon. Cancer Res, 69 (7): 2826-32. [PMID:19276343]

33. Tunaru S, Kero J, Schaub A, Wufka C, Blaukat A, Pfeffer K, Offermanns S. (2003) PUMA-G and HM74 are receptors for nicotinic acid and mediate its anti-lipolytic effect. Nat Med, 9 (3): 352-5. [PMID:12563315]

34. van Herk T, Brussee J, van den Nieuwendijk AM, van der Klein PA, IJzerman AP, Stannek C, Burmeister A, Lorenzen A. (2003) Pyrazole derivatives as partial agonists for the nicotinic acid receptor. J Med Chem, 46 (18): 3945-51. [PMID:12930155]

35. van Veldhoven JP, Blad CC, Artsen CM, Klopman C, Wolfram DR, Abdelkadir MJ, Lane JR, Brussee J, Ijzerman AP. (2011) Structure-activity relationships of trans-substituted-propenoic acid derivatives on the nicotinic acid receptor HCA2 (GPR109A). Bioorg Med Chem Lett, 21 (9): 2736-9. [PMID:21167710]

36. Wannick M, Assmann JC, Vielhauer JF, Offermanns S, Zillikens D, Sadik CD, Schwaninger M. (2018) The Immunometabolomic Interface Receptor Hydroxycarboxylic Acid Receptor 2 Mediates the Therapeutic Effects of Dimethyl Fumarate in Autoantibody-Induced Skin Inflammation. Front Immunol, 9: 1890. [PMID:30154797]

37. Wise A, Foord SM, Fraser NJ, Barnes AA, Elshourbagy N, Eilert M, Ignar DM, Murdock PR, Steplewski K, Green A et al.. (2003) Molecular identification of high and low affinity receptors for nicotinic acid. J Biol Chem, 278 (11): 9869-74. [PMID:12522134]

38. Zhang Y, Schmidt RJ, Foxworthy P, Emkey R, Oler JK, Large TH, Wang H, Su EW, Mosior MK, Eacho PI et al.. (2005) Niacin mediates lipolysis in adipose tissue through its G-protein coupled receptor HM74A. Biochem Biophys Res Commun, 334 (2): 729-32. [PMID:16018973]

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