Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5ZSESQ)

• DOT Name: Hydroxycarboxylic acid receptor 1 (HCAR1)
• Synonyms: G-protein coupled receptor 104; G-protein coupled receptor 81
• Gene Name: HCAR1
• UniProt ID: HCAR1_HUMAN
• Pfam ID: PF00001
• Sequence:
  MYNGSCCRIEGDTISQVMPPLLIVAFVLGALGNGVALCGFCFHMKTWKPSTVYLFNLAVA
  DFLLMICLPFRTDYYLRRRHWAFGDIPCRVGLFTLAMNRAGSIVFLTVVAADRYFKVVHP
  HHAVNTISTRVAAGIVCTLWALVILGTVYLLLENHLCVQETAVSCESFIMESANGWHDIM
  FQLEFFMPLGIILFCSFKIVWSLRRRQQLARQARMKKATRFIMVVAIVFITCYLPSVSAR
  LYFLWTVPSSACDPSVHGALHITLSFTYMNSMLDPLVYYFSSPSFPKFYNKLKICSLKPK
  QPGHSKTQRPEEMPISNLGRRSCISVANSFQSQSDGQWDPHIVEWH
• Function: Acts as a receptor for L-lactate and mediates its anti-lipolytic effect through a G(i)-protein-mediated pathway.
• Tissue Specificity: Expressed abundantly in brown and white fat. It also detectable at lower levels in liver, kidney, skeletal muscle, brain and pituitary. Not detected in frontal, temporal and occipital lobes of the cortex, basal forebrain, caudate nucleus, nucleus accumbens and hippocampus.
• KEGG Pathway: cAMP sig.ling 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 DOT

5 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Hydroxycarboxylic acid receptor 1 (HCAR1).	[1]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Hydroxycarboxylic acid receptor 1 (HCAR1).	[2]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Hydroxycarboxylic acid receptor 1 (HCAR1).	[3]
OTX-015	DMI8RG1	Phase 1/2	OTX-015 decreases the expression of Hydroxycarboxylic acid receptor 1 (HCAR1).	[5]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Hydroxycarboxylic acid receptor 1 (HCAR1).	[6]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Hydroxycarboxylic acid receptor 1 (HCAR1).	[4]

References

• [1] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [2] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [3] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [4] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [5] Comprehensive transcriptome profiling of BET inhibitor-treated HepG2 cells. PLoS One. 2022 Apr 29;17(4):e0266966. doi: 10.1371/journal.pone.0266966. eCollection 2022.
• [6] Synergistic effect of JQ1 and rapamycin for treatment of human osteosarcoma. Int J Cancer. 2015 May 1;136(9):2055-64.