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

General Information of Drug (ID: DMCPB0Q)

• Drug Name: LTE4 Drug Info
• Synonyms: Leukotriene E4; leukotriene E4; Leukotriene E; UNII-8EYT8ATL7G; 75715-89-8; 8EYT8ATL7G; CHEMBL509456; CHEBI:15650; OTZRAYGBFWZKMX-FRFVZSDQSA-N; 5S-hydroxy,6R-(S-cysteinyl),7E,9E,11Z,14Z-eicosatetraenoic acid; C23H37NO5S; (5S-(5R*,6S*(S*),7E,9E,11Z,14Z))-6-((2-Amino-2-carboxyethyl)thio)-5-hydroxy-7,9,11,14-eicosatetraenoic acid; (5S,6R,7E,9E,11Z,14Z)-6-[(2R)-2-amino-3-hydroxy-3-oxopropyl]sulfanyl-5-hydroxyicosa-7,9,11,14-tetraenoic acid; [3H]LTE4; AC1NQXPM; LEUKOTRIEN E4; BSPBio_001370; leukotriene E

Indication

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

• Cross-matching ID:
  PubChem CID: 5280879
  ChEBI ID: CHEBI:15650
  CAS Number: CAS 75715-89-8
  TTD Drug ID: DMCPB0Q
  VARIDT Drug ID: DR01485

Molecule-Related Drug Atlas

Drug(s) Targeting Uracil nucleotide/cysteinyl leukotriene receptor (GPR17)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
UDP-glucose	DMLT4JA	Discovery agent	N.A.	Investigative	[9]
LTC4	DM702WR	Discovery agent	N.A.	Investigative	[9]
LTD4	DMIUZX3	Discovery agent	N.A.	Investigative	[9]
ASN04421891	DMC82XN	Discovery agent	N.A.	Investigative	[10]
ASN04450772	DMKR69T	Discovery agent	N.A.	Investigative	[10]
ASN06917370	DMA20JP	Discovery agent	N.A.	Investigative	[10]
ASN02563583	DMEO3Y4	Discovery agent	N.A.	Investigative	[10]
ASN04885796	DMQ0VZ8	Discovery agent	N.A.	Investigative	[10]

Drug(s) Targeting Oxoglutarate receptor (OXGR1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
alpha-ketoglutaric acid	DM5LFYN	Discovery agent	N.A.	Investigative	[11]

Drug(s) Targeting Leukotriene CysLT1 receptor (CYSLTR1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Montelukast	DMD157S	Allergic asthma	CA23.0	Approved	[12]
Zafirlukast	DMHNQOG	Asthma	CA23	Approved	[13]
Pranlukast	DMYHDCA	Allergic rhinitis	CA08.0	Approved	[14]
Cinalukast	DMFIC0M	Asthma	CA23	Approved	[15]
KP-496	DMCO8UZ	Asthma	CA23	Phase 2	[16]
BAY-X-7195	DM2XE80	Asthma	CA23	Phase 2	[17]
Masilukast	DMDTI0L	Asthma	CA23	Phase 2	[18]
LM-1507.NA	DMW6VA0	Asthma	CA23	Phase 2	[19]
Iralukast	DMQ3RWN	Asthma	CA23	Phase 2	[20]
YM-57158	DMS31YW	Allergic rhinitis	CA08.0	Phase 1	[21]

Drug(s) Targeting Leukotriene CysLT2 receptor (CYSLTR2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BAY-X-7195	DM2XE80	Asthma	CA23	Phase 2	[17]
AS-35	DMC2WI7	Asthma	CA23	Discontinued in Phase 2	[22]
DS-4574	DM8GZWC	Asthma	CA23	Discontinued in Phase 2	[23]
Sulukast	DMBSLZV	Asthma	CA23	Discontinued in Phase 2	[24]
ICI-198615	DM0195G	Asthma	CA23	Terminated	[25]
MDL-43291	DMBIDQX	Asthma	CA23	Terminated	[26]
LY-290154	DMPZ7AO	Asthma	CA23	Terminated	[27]
FPL-55712	DMF1CDK	Asthma	CA23	Terminated	[28]
LTC4	DM702WR	Discovery agent	N.A.	Investigative	[29]
LTD4	DMIUZX3	Discovery agent	N.A.	Investigative	[29]

Drug(s) Transported By Multidrug resistance-associated protein 1 (ABCC1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[30]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[31]
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[32]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[33]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[34]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[35]
Irinotecan	DMP6SC2	Adenocarcinoma	2D40	Approved	[36]
Glutathione	DMAHMT9	Human immunodeficiency virus infection	1C62	Approved	[37]
Phenytoin	DMNOKBV	Epilepsy	8A60-8A68	Approved	[38]
Daunorubicin	DMQUSBT	Acute monocytic leukemia		Approved	[39]

Drug(s) Transported By Organic anion transporting polypeptide 1B1 (SLCO1B1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[40]
Dinoprostone	DMTYOPD	Medical abortion	JA00.1Z	Approved	[7]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[41]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[42]
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[41]
Pravastatin	DM6A0X7	Adult acute monocytic leukemia		Approved	[43]
Mycophenolate mofetil	DMPQAGE	Hepatosplenic T-cell lymphoma		Approved	[44]
Atorvastatin	DMF28YC	Acute coronary syndrome	BA41	Approved	[45]
Cerivastatin	DMXCM7H	Hyperlipidaemia	5C80	Approved	[46]
PITAVASTATIN CALCIUM	DM1UJO0	Dyslipidemia	5C80-5C81	Approved	[43]

Drug(s) Affected By Cysteinyl leukotriene receptor 1 (CYSLTR1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Zafirlukast	DMHNQOG	Asthma	CA23	Approved	[47]
Pranlukast	DMYHDCA	Allergic rhinitis	CA08.0	Approved	[47]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[48]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[49]
Aspirin	DM672AH	Acute coronary syndrome	BA41	Approved	[50]
(+)-JQ1	DM1CZSJ	Testicular cancer	2C80	Phase 1	[51]
PMID28870136-Compound-48	DMPIM9L	N. A.	N. A.	Patented	[48]
LTC4	DM702WR	Discovery agent	N.A.	Investigative	[47]
BAYu9773	DMXQ14V	Discovery agent	N.A.	Investigative	[47]
CGP-57698	DMYZ72J	Discovery agent	N.A.	Investigative	[47]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Leukotriene CysLT1 receptor (CYSLTR1)	TTGKOY9	CLTR1_HUMAN	Agonist	[2]
Leukotriene CysLT2 receptor (CYSLTR2)	TT0PZR5	CLTR2_HUMAN	Agonist	[3]
Oxoglutarate receptor (OXGR1)	TTAS1QK	OXGR1_HUMAN	Agonist	[4]
Uracil nucleotide/cysteinyl leukotriene receptor (GPR17)	TTMPART	GPR17_HUMAN	Agonist	[5]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Multidrug resistance-associated protein 1 (ABCC1)	DTSYQGK	MRP1_HUMAN	Substrate	[6]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[7]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Cysteinyl leukotriene receptor 1 (CYSLTR1)	OT904HBN	CLTR1_HUMAN	Protein Interaction/Cellular Processes	[8]

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: 5863).
• [2] Characterization of the human cysteinyl leukotriene CysLT1 receptor. Nature. 1999 Jun 24;399(6738):789-93.
• [3] Differential signaling of cysteinyl leukotrienes and a novel cysteinyl leukotriene receptor 2 (CysLT agonist, N-methyl-leukotriene C in calcium reporter and beta arrestin assays. Mol Pharmacol. 2011 Feb;79(2):270-8.
• [4] Identification of GPR99 protein as a potential third cysteinyl leukotriene receptor with a preference for leukotriene E4 ligand. J Biol Chem. 2013 Apr 19;288(16):10967-72.
• [5] The recently identified P2Y-like receptor GPR17 is a sensor of brain damage and a new target for brain repair. PLoS One. 2008;3(10):e3579.
• [6] Transport of glutathione, glucuronate, and sulfate conjugates by the MRP gene-encoded conjugate export pump. Cancer Res. 1996 Mar 1;56(5):988-94.
• [7] Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. Pharmacol Rev. 2011 Mar;63(1):157-81.
• [8] Characterization of the leukotriene D4 receptor in dimethylsulphoxide-differentiated U937 cells: comparison with the leukotriene D4 receptor in human lung and guinea-pig lung. Eur J Pharmacol. 1993 Feb 15;244(3):239-50. doi: 10.1016/0922-4106(93)90149-4.
• [9] The orphan receptor GPR17 identified as a new dual uracil nucleotides/cysteinyl-leukotrienes receptor. EMBO J. 2006 Oct 4;25(19):4615-27.
• [10] In silico identification of new ligands for GPR17: a promising therapeutic target for neurodegenerative diseases. J Comput Aided Mol Des. 2011 Aug;25(8):743-52.
• [11] 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.
• [12] Protective potential of montelukast against hepatic ischemia/reperfusion injury in rats. J Surg Res. 2010 Mar;159(1):588-94.
• [13] Inhibitory effects of zafirlukast on respiratory bursts of human neutrophils. Drugs Exp Clin Res. 2002;28(4):133-45.
• [14] Beneficial effects of leukotriene receptor antagonists in the prevention of cedar pollinosis in a community setting. J Investig Allergol Clin Immunol. 2009;19(3):195-203.
• [15] Prolonged protection against exercise-induced bronchoconstriction by the leukotriene D4-receptor antagonist cinalukast. J Allergy Clin Immunol. 1997 Feb;99(2):210-5.
• [16] Effects of KP-496, a novel dual antagonist for leukotriene D4 and thromboxane A2 receptors, on contractions induced by various agonists in the guinea pig trachea. Allergol Int. 2006 Dec;55(4):403-10.
• [17] The effect of a novel leukotriene C4/D4 antagonist, BAY-x-7195, on experimental allergic reactions. Prostaglandins. 1995 Nov-Dec;50(5-6):269-85.
• [18] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [19] Pharmacological differences among CysLT(1) receptor antagonists with respect to LTC(4) and LTD(4) in human lung parenchyma. Biochem Pharmacol. 2002 Apr 15;63(8):1537-46.
• [20] Pharmacological characterization of the cysteinyl-leukotriene antagonists CGP 45715A (iralukast) and CGP 57698 in human airways in vitro. Br J Pharmacol. 1998 Feb;123(3):590-8.
• [21] In vitro pharmacologic profile of YM158, a new dual antagonist for LTD4 and TXA2 receptors. J Pharmacol Exp Ther. 1998 Nov;287(2):633-9.
• [22] Inhibition of radiolabeled leukotriene-binding by AS-35 in guinea pig lung membrane fraction. Jpn J Pharmacol. 1992 Apr;58(4):357-64.
• [23] Inhibitory effect of DS-4574, a mast cell stabilizer with peptidoleukotriene receptor antagonism, on gastric acid secretion in rats. Eur J Pharmacol. 1994 Apr 1;255(1-3):229-34.
• [24] The pharmacological evaluation of LY 170680, a novel leukotriene D4 and E4 antagonist in the guinea-pig. Br J Pharmacol. 1989 Sep;98(1):259-67.
• [25] Heterogeneity of binding sites for ICI 198,615 in human lung parenchyma. Biochem Pharmacol. 1992 Oct 6;44(7):1411-5.
• [26] Conformationally restricted leukotriene receptor antagonists: [(octahydro-2-oxo-7-tetradecylidene-2H-1-benzopyran-8-yl)thio]ace tic acids. Pharmacology. 1990;40(5):271-6.
• [27] DOI: 10.1021/op060036x
• [28] Effect of the leukotriene receptor antagonists FPL 55712, LY 163443, and MK-571 on the elimination of cysteinyl leukotrienes in the rat. Br J Pharmacol. 1991 Apr;102(4):865-70.
• [29] Molecular cloning and characterization of a second human cysteinyl leukotriene receptor: discovery of a subtype selective agonist. Mol Pharmacol. 2000 Dec;58(6):1601-8.
• [30] The role of bioreductive activation of doxorubicin in cytotoxic activity against leukaemia HL60-sensitive cell line and its multidrug-resistant sublines. Br J Cancer. 2005 Jul 11;93(1):89-97.
• [31] Transport of methotrexate (MTX) and folates by multidrug resistance protein (MRP) 3 and MRP1: effect of polyglutamylation on MTX transport. Cancer Res. 2001 Oct 1;61(19):7225-32.
• [32] Folate concentration dependent transport activity of the Multidrug Resistance Protein 1 (ABCC1). Biochem Pharmacol. 2004 Apr 15;67(8):1541-8.
• [33] Hammerhead ribozyme against gamma-glutamylcysteine synthetase sensitizes human colonic cancer cells to cisplatin by down-regulating both the glutathione synthesis and the expression of multidrug resistance proteins. Cancer Gene Ther. 2001 Oct;8(10):803-14.
• [34] Multidrug resistance-associated protein-1 functional activity in Calu-3 cells. J Pharmacol Exp Ther. 2001 Sep;298(3):1199-205.
• [35] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [36] ATP-Dependent efflux of CPT-11 and SN-38 by the multidrug resistance protein (MRP) and its inhibition by PAK-104P. Mol Pharmacol. 1999 May;55(5):921-8.
• [37] Structural determinants of substrate specificity differences between human multidrug resistance protein (MRP) 1 (ABCC1) and MRP3 (ABCC3). Drug Metab Dispos. 2008 Dec;36(12):2571-81.
• [38] Evaluation of transport of common antiepileptic drugs by human multidrug resistance-associated proteins (MRP1, 2 and 5) that are overexpressed in pharmacoresistant epilepsy. Neuropharmacology. 2010 Jun;58(7):1019-32.
• [39] Vinblastine and sulfinpyrazone export by the multidrug resistance protein MRP2 is associated with glutathione export. Br J Cancer. 2000 Aug;83(3):375-83.
• [40] Preclinical Mouse Models To Study Human OATP1B1- and OATP1B3-Mediated Drug-Drug Interactions in Vivo. Mol Pharm. 2015 Dec 7;12(12):4259-69.
• [41] Contribution of OATP1B1 and OATP1B3 to the disposition of sorafenib and sorafenib-glucuronide. Clin Cancer Res. 2013 Mar 15;19(6):1458-66.
• [42] Identification of drugs and drug metabolites as substrates of multidrug resistance protein 2 (MRP2) using triple-transfected MDCK-OATP1B1-UGT1A1-MRP2 cells. Br J Pharmacol. 2012 Mar;165(6):1836-1847.
• [43] The effect of SLCO1B1*15 on the disposition of pravastatin and pitavastatin is substrate dependent: the contribution of transporting activity changes by SLCO1B1*15. Pharmacogenet Genomics. 2008 May;18(5):424-33.
• [44] Influence of SLCO1B1, 1B3, 2B1 and ABCC2 genetic polymorphisms on mycophenolic acid pharmacokinetics in Japanese renal transplant recipients. Eur J Clin Pharmacol. 2007 Dec;63(12):1161-9.
• [45] Rifampicin alters atorvastatin plasma concentration on the basis of SLCO1B1 521T>C polymorphism. Clin Chim Acta. 2009 Jul;405(1-2):49-52.
• [46] FDA Drug Development and Drug Interactions
• [47] A kinetic binding study to evaluate the pharmacological profile of a specific leukotriene C(4) binding site not coupled to contraction in human lun... Mol Pharmacol. 2000 Jun;57(6):1182-9.
• [48] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [49] 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.
• [50] Differential contribution of the CysLTR1 gene in patients with aspirin hypersensitivity. J Clin Immunol. 2007 Nov;27(6):613-9. doi: 10.1007/s10875-007-9115-x. Epub 2007 Jul 20.
• [51] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.