Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMB1WEY)

• DOT Name: Glucagon-like peptide 1 receptor (GLP1R)
• Synonyms: GLP-1 receptor; GLP-1-R; GLP-1R
• Gene Name: GLP1R
• UniProt ID: GLP1R_HUMAN
• PDB ID: 3C59 ; 3C5T ; 3IOL ; 4ZGM ; 5E94 ; 5NX2 ; 5OTT ; 5OTU ; 5OTV ; 5OTW ; 5OTX ; 5VEW ; 5VEX ; 6B3J ; 6GB1 ; 6ORV ; 6VCB ; 6X18 ; 6X19 ; 6X1A ; 6XOX ; 7C2E ; 7DUQ ; 7DUR ; 7E14 ; 7EVM ; 7FIM ; 7KI0 ; 7KI1 ; 7LCI ; 7LCJ ; 7LCK ; 7LLL ; 7LLY ; 7RG9 ; 7RGP ; 7RTB ; 7S15 ; 7S1M ; 7S3I ; 7VBH ; 7VBI ; 7X8R ; 7X8S ; 8JIP ; 8JIR ; 8JIS
• Pfam ID: PF00002 ; PF02793
• Sequence:
  MAGAPGPLRLALLLLGMVGRAGPRPQGATVSLWETVQKWREYRRQCQRSLTEDPPPATDL
  FCNRTFDEYACWPDGEPGSFVNVSCPWYLPWASSVPQGHVYRFCTAEGLWLQKDNSSLPW
  RDLSECEESKRGERSSPEEQLLFLYIIYTVGYALSFSALVIASAILLGFRHLHCTRNYIH
  LNLFASFILRALSVFIKDAALKWMYSTAAQQHQWDGLLSYQDSLSCRLVFLLMQYCVAAN
  YYWLLVEGVYLYTLLAFSVLSEQWIFRLYVSIGWGVPLLFVVPWGIVKYLYEDEGCWTRN
  SNMNYWLIIRLPILFAIGVNFLIFVRVICIVVSKLKANLMCKTDIKCRLAKSTLTLIPLL
  GTHEVIFAFVMDEHARGTLRFIKLFTELSFTSFQGLMVAILYCFVNNEVQLEFRKSWERW
  RLEHLHIQRDSSMKPLKCPTSSLSSGATAGSSMYTATCQASCS
• Function: G-protein coupled receptor for glucagon-like peptide 1 (GLP-1). Ligand binding triggers activation of a signaling cascade that leads to the activation of adenylyl cyclase and increased intracellular cAMP levels. Plays a role in regulating insulin secretion in response to GLP-1.
• KEGG Pathway:
  cAMP sig.ling pathway (hsa04024)
  Neuroactive ligand-receptor interaction (hsa04080)
  Insulin secretion (hsa04911)
• Reactome Pathway:
  G alpha (s) signalling events (R-HSA-418555)
  Glucagon-type ligand receptors (R-HSA-420092)
  Glucagon-like Peptide-1 (GLP1) regulates insulin secretion (R-HSA-381676)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Glucagon-like peptide 1 receptor (GLP1R).	[1]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Glucagon-like peptide 1 receptor (GLP1R).	[2]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Glucagon-like peptide 1 receptor (GLP1R).	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Glucagon-like peptide 1 receptor (GLP1R).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Glucagon-like peptide 1 receptor (GLP1R).	[5]

References

• [1] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [2] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [3] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [4] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [5] 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.