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

General Information of Drug (ID: DMETM3R)

• Drug Name: lysophosphatidylinositol Drug Info
• Synonyms: LPI; L-alpha-lysophosphatidylinositol

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 73755067
  TTD Drug ID: DMETM3R

Molecule-Related Drug Atlas

Drug(s) Targeting Transient receptor potential cation channel V2 (TRPV2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
[14C]TEA	DM6SFYH	Discovery agent	N.A.	Investigative	[6]
2-APB	DM9AKVR	Discovery agent	N.A.	Investigative	[6]
lysophosphatidylcholine	DMOGFVH	Discovery agent	N.A.	Investigative	[4]
diphenylboronic anhydride	DMRQZTS	Discovery agent	N.A.	Investigative	[6]
citral	DM53ZGY	Discovery agent	N.A.	Investigative	[7]
cannabinol	DMM6A7P	Discovery agent	N.A.	Investigative	[8]
TRIM	DMNHU4M	Discovery agent	N.A.	Investigative	[6]

Drug(s) Targeting G-protein coupled receptor 55 (GPR55)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Guanfacine extended release	DMB1CZ8	Attention deficit hyperactivity disorder	6A05.Z	Approved	[9]
BIO-017	DMYHK3Y	Angelman syndrome	LD90.0	Phase 1	[10]
N-oleoylethanolamide	DMJQ4L7	Discovery agent	N.A.	Investigative	[9]
[3H]CP55940	DMU7FC5	Discovery agent	N.A.	Investigative	[9]
O-1602	DM9VISB	Discovery agent	N.A.	Investigative	[11]
abnormal cannabidiol	DMV6DAO	Discovery agent	N.A.	Investigative	[9]
O-arachidonoyl ethanolamine	DML0P72	Discovery agent	N.A.	Investigative	[9]
CID1172084	DMK6YOP	Discovery agent	N.A.	Investigative	[12]
CID16020046	DMLWZRT	Discovery agent	N.A.	Investigative	[13]
2-arachidonyl glyceryl ether	DM2H8TV	Discovery agent	N.A.	Investigative	[9]

Drug(s) Targeting Glucose-dependent insulinotropic receptor (GPR119)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Guanfacine extended release	DMB1CZ8	Attention deficit hyperactivity disorder	6A05.Z	Approved	[14]
DS-8500	DMUXIRM	Diabetic complication	5A2Y	Phase 2	[15]
SAR-260093	DMBJU2G	Type-2 diabetes	5A11	Phase 2	[16]
GSK1292263	DMDMXKQ	Gastric adenocarcinoma	2B72	Phase 2	[17]
BMS-903452	DM7JW0B	Type-2 diabetes	5A11	Phase 1	[18]
APD-597	DM36FOG	Type-2 diabetes	5A11	Phase 1	[19]
DA-1241	DMPJA64	Type 2 diabetes	5A11	Phase 1	[20]
APD668	DMN8R2U	Type-2 diabetes	5A11	Discontinued in Phase 1	[21]
PSN821	DMGEWUS	Type-2 diabetes	5A11	Terminated	[22]
N-oleoylethanolamide	DMJQ4L7	Discovery agent	N.A.	Investigative	[2]

Drug(s) Affected By Serum paraoxonase/arylesterase 1 (PON1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Primidone	DM0WX6I	Epilepsy	8A60-8A68	Approved	[23]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[24]
Methimazole	DM25FL8	Hyperthyroidism	5A02	Approved	[25]
Ciprofloxacin XR	DM2NLS9	Acute gonococcal cervicitis		Approved	[26]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[27]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[28]
Panobinostat	DM58WKG	Chronic graft versus host disease		Approved	[29]
Rifampicin	DM5DSFZ	Non-insulin dependent diabetes	5A11	Approved	[30]
Aspirin	DM672AH	Acute coronary syndrome	BA41	Approved	[31]
Gabapentin	DM6T924	Complex partial seizure	8A68.0	Approved	[23]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
G-protein coupled receptor 55 (GPR55)	TTNET8J	GPR55_HUMAN	Agonist	[2]
Glucose-dependent insulinotropic receptor (GPR119)	TT7QNVC	GP119_HUMAN	Agonist	[3]
Transient receptor potential cation channel V2 (TRPV2)	TTBECWA	TRPV2_HUMAN	Activator	[4]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Serum paraoxonase/arylesterase 1 (PON1)	OTD0Z2XO	PON1_HUMAN	Gene/Protein Processing	[5]

References

• [1] 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: 4028).
• [2] Screening beta-arrestin recruitment for the identification of natural ligands for orphan G-protein-coupled receptors. J Biomol Screen. 2013 Jun;18(5):599-609.
• [3] Lysophosphatidylcholine enhances glucose-dependent insulin secretion via an orphan G-protein-coupled receptor. Biochem Biophys Res Commun. 2005 Jan 28;326(4):744-51.
• [4] Lysophospholipids stimulate prostate cancer cell migration via TRPV2 channel activation. Biochim Biophys Acta. 2009 Mar;1793(3):528-39.
• [5] Preferential inhibition of paraoxonase activity of human paraoxonase 1 by negatively charged lipids. J Lipid Res. 2004 Dec;45(12):2211-20.
• [6] Pharmacological characterization and molecular determinants of the activation of transient receptor potential V2 channel orthologs by 2-aminoethoxy... Mol Pharmacol. 2007 Nov;72(5):1258-68.
• [7] Citral sensing by Transient [corrected] receptor potential channels in dorsal root ganglion neurons. PLoS One. 2008 May 7;3(5):e2082.
• [8] TRPV2 is activated by cannabidiol and mediates CGRP release in cultured rat dorsal root ganglion neurons. J Neurosci. 2008 Jun 11;28(24):6231-8.
• [9] The orphan receptor GPR55 is a novel cannabinoid receptor. Br J Pharmacol. 2007 Dec;152(7):1092-101.
• [10] Clinical pipeline report, company report or official report of Biom Therapeutics
• [11] International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid receptors and their ligands: beyond CB and CB Pharmacol Rev. 2010 Dec;62(4):588-631.
• [12] Identification of the GPR55 agonist binding site using a novel set of high-potency GPR55 selective ligands. Biochemistry. 2011 Jun 28;50(25):5633-47.
• [13] A selective antagonist reveals a potential role of G protein-coupled receptor 55 in platelet and endothelial cell function. J Pharmacol Exp Ther. 2013 Jul;346(1):54-66.
• [14] 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: 126).
• [15] Addressing Unmet Medical Needs in Type 2 Diabetes: A Narrative Review of Drugs under Development. Curr Diabetes Rev. 2015 March; 11(1): 17-31.
• [16] GPR119 agonists for the treatment of type 2 diabetes. Expert Opin Ther Pat. 2009 Oct;19(10):1339-59.
• [17] Gut hormone pharmacology of a novel GPR119 agonist (GSK1292263), metformin, and sitagliptin in type 2 diabetes mellitus: results from two randomized studies.PLoS One.2014 Apr 3;9(4):e92494.
• [18] Discovery of 5-chloro-4-((1-(5-chloropyrimidin-2-yl)piperidin-4-yl)oxy)-1-(2-fluoro-4-(methylsulfonyl)phenyl)pyridin-2(1H)-one (BMS-903452), an antidiabetic clinical candidate targeting GPR119. J MedChem. 2014 Sep 25;57(18):7499-508.
• [19] Discovery of a second generation agonist of the orphan G-protein coupled receptor GPR119 with an improved profile. Bioorg Med Chem Lett. 2012 Feb 15;22(4):1750-5.
• [20] ClinicalTrials.gov (NCT03646721) A Study to Evaluate the Safety, Tolerability, PK and PD of DA-1241 in Healthy Male Subjects and Subjects With T2DM. U.S. National Institutes of Health.
• [21] Announces Initiation of Phase 1 Clinical Trial of Arena Type 2 Diabetes Drug Candidate in Collaboration With Ortho-McNeil. Arena Pharmaceuticals, Inc. FEBRUARY 07, 2006.
• [22] Clinical pipeline report, company report or official report of Astellas Pharma (2011).
• [23] Antiepileptic drugs: impacts on human serum paraoxonase-1. J Biochem Mol Toxicol. 2017 Jun;31(6).
• [24] Beneficial effect of oleoylated lipids on paraoxonase 1: protection against oxidative inactivation and stabilization. Biochem J. 2003 Oct 15;375(Pt 2):275-85.
• [25] Serum paraoxonase activity before and after treatment of thyrotoxicosis. Clin Endocrinol (Oxf). 2004 Jan;60(1):75-80.
• [26] Effects of some antibiotics on paraoxonase from human serum in vitro and from mouse serum and liver in vivo. Biol Pharm Bull. 2006 Aug;29(8):1559-63.
• [27] Simvastatin modulates expression of the PON1 gene and increases serum paraoxonase: a role for sterol regulatory element-binding protein-2. Arterioscler Thromb Vasc Biol. 2003 Nov 1;23(11):2083-9. doi: 10.1161/01.ATV.0000096207.01487.36. Epub 2003 Sep 18.
• [28] Dietary polyphenols increase paraoxonase 1 gene expression by an aryl hydrocarbon receptor-dependent mechanism. Mol Cell Biol. 2004 Jun;24(12):5209-22.
• [29] 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.
• [30] Transcriptional regulation of human paraoxonase 1 by PXR and GR in human hepatoma cells. Toxicol In Vitro. 2015 Dec 25;30(1 Pt B):348-54.
• [31] Induction of paraoxonase 1 and apolipoprotein A-I gene expression by aspirin. J Lipid Res. 2008 Oct;49(10):2142-8.