Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DM3FXPS)

• Drug Name: Liraglutide Drug Info
• Synonyms: Liraglutida; Liraglutidum; Victoza; NN 2211; NN2211; Liraglutida [INN-Spanish]; Liraglutide [USAN:INN]; Liraglutidum [INN-Latin]; NN-2211; Victoza (TN); N26-(Hexadecanoyl-gamma-glutamyle)-(34-arginine)GLP-1-(7-37)-peptide; N26-(Hexadecanoyl-gamma-glutamyle)-(34-arginine)glucagon-like-peptide-1-(7-37)-peptide

Indication

Disease Entry	ICD 11	Status	REF
Non-insulin dependent diabetes	5A11	Approved	[1]
Type-2 diabetes	5A11	Approved	[2]
Obesity	5B81	Phase 2	[2]

• Cross-matching ID:
  PubChem CID: 16134956
  ChEBI ID: CHEMBL4084119
  CAS Number: CAS 204656-20-2
  TTD Drug ID: DM3FXPS
  INTEDE Drug ID: DR0962

Molecule-Related Drug Atlas

Drug(s) Targeting Glucagon-like peptide 1 receptor (GLP1R)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Semaglutide	DMAGFOD	Type-2 diabetes	5A11	Approved	[6]
Exenatide	DMYHBKN	Inflammation	1A00-CA43.1	Approved	[7]
Dulaglutide	DMYXBV3	Type-2 diabetes	5A11	Approved	[8]
Lixisenatide	DM0QJDC	Type-2 diabetes	5A11	Approved	[9]
Pramlintide	DM0EZ9Q	Type-1/2 diabetes	5A10-5A11	Approved	[3]
Albiglutide	DM1JEGF	Type-2 diabetes	5A11	Approved	[9]
Tirzepatide	DMQNMAT	Type 2 diabetes	5A11	Approved	[10]
Efpeglenatide	DMKA2PI	Type-2 diabetes	5A11	Phase 3	[11]
GLP-1	DMR6YH3	Diabetic complication	5A2Y	Phase 3	[6]
Taspoglutide	DMPYET9	Type-1 diabetes	5A10	Phase 3	[12]

Drug(s) Metabolized By Dipeptidyl peptidase IV (DPP4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Semaglutide	DMAGFOD	Type-2 diabetes	5A11	Approved	[13]
Exenatide	DMYHBKN	Inflammation	1A00-CA43.1	Approved	[14]

Drug(s) Metabolized By Neprilysin (MME)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Semaglutide	DMAGFOD	Type-2 diabetes	5A11	Approved	[13]

Drug(s) Affected By Cadherin-1 (CDH1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Beta-carotene	DM0RXBT	Vitamin deficiency	5B55-5B71	Approved	[15]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[16]
Nitric Oxide	DM1RBYG	Hypertension	BA00-BA04	Approved	[17]
Colchicine	DM2POTE	Acute gout flare	FA25.0	Approved	[18]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[19]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[20]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[21]
Polyethylene glycol	DM4I1JP	Constipation	DD91.1	Approved	[22]
Panobinostat	DM58WKG	Chronic graft versus host disease		Approved	[23]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[24]

Drug(s) Affected By Disintegrin and metalloproteinase domain-containing protein 33 (ADAM33)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[25]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[26]
Decitabine	DMQL8XJ	Acute myelogenous leukaemia	2A41	Approved	[5]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[27]
Triclosan	DMZUR4N	Malaria	1F40-1F45	Approved	[28]
Aspirin	DM672AH	Acute coronary syndrome	BA41	Approved	[29]
Benzo(a)pyrene	DMN7J43	N. A.	N. A.	Phase 1	[30]
Sulforaphane	DMQY3L0	Skin disease	EA00-EM0Z	Investigative	[31]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Glucagon-like peptide 1 receptor (GLP1R)	TTVIMDE	GLP1R_HUMAN	Agonist	[3]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Neprilysin (MME)	DEVN830	NEP_HUMAN	Substrate	[4]
Dipeptidyl peptidase IV (DPP4)	DEKZQY6	DPP4_HUMAN	Substrate	[4]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Cadherin-1 (CDH1)	OTFJMXPM	CADH1_HUMAN	Gene/Protein Processing	[5]
Disintegrin and metalloproteinase domain-containing protein 33 (ADAM33)	OTRZVI77	ADA33_HUMAN	Gene/Protein Processing	[5]

References

• [1] Liraglutide FDA Label
• [2] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 1133).
• [3] Emerging drugs for obesity: linking novel biological mechanisms to pharmaceutical pipelines. Expert Opin Emerg Drugs. 2005 Aug;10(3):643-60.
• [4] Metabolism and excretion of the once-daily human glucagon-like peptide-1 analog liraglutide in healthy male subjects and its in vitro degradation by dipeptidyl peptidase IV and neutral endopeptidase. Drug Metab Dispos. 2010 Nov;38(11):1944-53.
• [5] Antitumoral activity of liraglutide, a new DNMT inhibitor in breast cancer cells in vitro and in vivo. Chem Biol Interact. 2021 Nov 1;349:109641. doi: 10.1016/j.cbi.2021.109641. Epub 2021 Sep 14.
• [6] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 249).
• [7] Improved glycemic control and reduction of cardiometabolic risk factors in subjects with type 2 diabetes and metabolic syndrome treated with exenatide in a clinical practice setting. Diabetes TechnolTher. 2009 Jun;11(6):353-9.
• [8] 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
• [9] GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus.Nat Rev Endocrinol.2012 Dec;8(12):728-42.
• [10] Dual GIP and GLP-1 Receptor Agonist Tirzepatide Improves Beta-cell Function and Insulin Sensitivity in Type 2 Diabetes. J Clin Endocrinol Metab. 2021 Jan 23;106(2):388-396.
• [11] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [12] Pharmacokinetic and pharmacodynamic properties of taspoglutide, a once-weekly, human GLP-1 analogue, after single-dose administration in patients with Type 2 diabetes. Diabet Med. 2009 Nov;26(11):1156-64.
• [13] Absorption, metabolism and excretion of the GLP-1 analogue semaglutide in humans and nonclinical species. Eur J Pharm Sci. 2017 Jun 15;104:31-41.
• [14] In vitro metabolic stability of exendin-4: pharmacokinetics and identification of cleavage products. PLoS One. 2015 Feb 27;10(2):e0116805.
• [15] Beta-carotene and apocarotenals promote retinoid signaling in BEAS-2B human bronchioepithelial cells. Arch Biochem Biophys. 2006 Nov 1;455(1):48-60.
• [16] Manganese superoxide dismutase induces migration and invasion of tongue squamous cell carcinoma via H2O2-dependent Snail signaling. Free Radic Biol Med. 2012 Jul 1;53(1):44-50. doi: 10.1016/j.freeradbiomed.2012.04.031. Epub 2012 May 9.
• [17] Nitric oxide causes anoikis through attenuation of E-cadherin and activation of caspase-3 in human gastric carcinoma AZ-521 cells infected with Mycoplasma hyorhinis. J Vet Med Sci. 2010 Jul;72(7):869-74.
• [18] Induced differentiation in HT29, a human colon adenocarcinoma cell line. J Cell Sci. 1999 Aug;112 ( Pt 16):2657-66. doi: 10.1242/jcs.112.16.2657.
• [19] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [20] Troglitazone increases expression of E-cadherin and claudin 4 in human pancreatic cancer cells. Biochem Biophys Res Commun. 2009 Mar 13;380(3):614-9. doi: 10.1016/j.bbrc.2009.01.134. Epub 2009 Jan 27.
• [21] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [22] Regulation of epithelial cell morphology and functions approaching to more in vivo-like by modifying polyethylene glycol on polysulfone membranes. PLoS One. 2012;7(4):e36110.
• [23] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [24] Autocrine human growth hormone increases sensitivity of mammary carcinoma cell to arsenic trioxide-induced apoptosis. Mol Cell Endocrinol. 2013 Sep 5;377(1-2):84-92. doi: 10.1016/j.mce.2013.07.002. Epub 2013 Jul 10.
• [25] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [26] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [27] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [28] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [29] ADAM33 polymorphisms are associated with aspirin-intolerant asthma in the Japanese population. J Hum Genet. 2007;52(1):66-72. doi: 10.1007/s10038-006-0081-6. Epub 2006 Oct 24.
• [30] 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.
• [31] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.