Details of the Drug

General Information of Drug (ID: DMIUZX3)

• Drug Name: LTD4
• Synonyms: S-[(4S,5R,6E,8E,10Z,13Z)-1-Carboxy-4-hydroxynonadeca-6,8,10,13-tetraen-5-yl]cysteinylglycine; 5(S)-Hydroxy-6(R)-S-cysteinylglycinyl-7-trans-9-trans-11-cis-14-cis-eicosatetraenoic Acid; Leukotriene D(sub 4); (5S,6R,7E,9E,11Z,14Z)-6-({2-amino-2-[(carboxymethyl)carbamoyl]ethyl}sulfanyl)-5-hydroxyicosa-7,9,11,14-tetraenoic acid; LTD (sub 4); [3H]LTD4; [3H]-LTD4; S-[(4S,5R,6E,8E,10Z,13Z)-1-carboxy-4-hydroxynonadeca-6,8,10,13-tetraen-5-yl]cysteinylglycine; AC1O5JI4; SCHEMBL4295683; GTPL3412; BML1-E08; GTPL3353; CHEMBL1521056; DTXSID6040533; YEESKJGWJFYOOK-LDDGIIIKSA-N; 73836-78-9; LTD; leukotriene D4

Indication

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

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 1:
  Molecular Weight (mw); 496.7
  Logarithm of the Partition Coefficient (xlogp); 1.4
  Rotatable Bond Count (rotbonds); 20
  Hydrogen Bond Donor Count (hbonddonor); 5
  Hydrogen Bond Acceptor Count (hbondacc); 8
• Chemical Identifiers:
  Formula: C25H40N2O6S
  IUPAC Name: (5S,6R,7E,9E,11Z,14Z)-6-[(2R)-2-amino-3-(carboxymethylamino)-3-oxopropyl]sulfanyl-5-hydroxyicosa-7,9,11,14-tetraenoic acid
  Canonical SMILES: CCCCC/C=C\\C/C=C\\C=C\\C=C\\[C@H]([C@H](CCCC(=O)O)O)SC[C@@H](C(=O)NCC(=O)O)N
  InChI: InChI=1S/C25H40N2O6S/c1-2-3-4-5-6-7-8-9-10-11-12-13-16-22(21(28)15-14-17-23(29)30)34-19-20(26)25(33)27-18-24(31)32/h6-7,9-13,16,20-22,28H,2-5,8,14-15,17-19,26H2,1H3,(H,27,33)(H,29,30)(H,31,32)/b7-6-,10-9-,12-11+,16-13+/t20-,21-,22+/m0/s1
  InChIKey: YEESKJGWJFYOOK-IJHYULJSSA-N
• Cross-matching ID:
  PubChem CID: 5280878
  ChEBI ID: CHEBI:28666
  CAS Number: 73836-78-9
  DrugBank ID: DB11858
  TTD ID: D03YBH

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]
Uracil nucleotide/cysteinyl leukotriene receptor (GPR17)	TTMPART	GPR17_HUMAN	Agonist	[4]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Cysteinyl leukotriene receptor 1 (CYSLTR1)	OT904HBN	CLTR1_HUMAN	Drug Response	[5]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Protein Interaction/Cellular Processes	[6]
P-selectin (SELP)	OTWR90PK	LYAM3_HUMAN	Gene/Protein Processing	[7]
Polyunsaturated fatty acid 5-lipoxygenase (ALOX5)	OT7FOIK2	LOX5_HUMAN	Regulation of Drug Effects	[8]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Protein Interaction/Cellular Processes	[6]
Tumor necrosis factor receptor superfamily member 6 (FAS)	OTP9XG86	TNR6_HUMAN	Gene/Protein Processing	[9]

Molecular Expression Atlas of This Drug

• The Studied Disease: Discovery agent
• ICD Disease Classification: N.A.

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Leukotriene CysLT1 receptor (CYSLTR1)	DTT	CYSLTR1	1.96E-02	0.24	0.43
Leukotriene CysLT2 receptor (CYSLTR2)	DTT	CYSLTR2	1.40E-03	-0.24	-0.52

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: 3412).
• [2] Identification, molecular cloning, expression, and characterization of a cysteinyl leukotriene receptor. Mol Pharmacol. 1999 Sep;56(3):657-63.
• [3] 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.
• [4] The orphan receptor GPR17 identified as a new dual uracil nucleotides/cysteinyl-leukotrienes receptor. EMBO J. 2006 Oct 4;25(19):4615-27.
• [5] Effects of the cysteinyl leukotriene receptor antagonists pranlukast and zafirlukast on tracheal mucus secretion in ovalbumin-sensitized guinea-pigs in vitro. Br J Pharmacol. 1998 Jun;124(3):563-71. doi: 10.1038/sj.bjp.0701886.
• [6] Leukotriene pathways and in vitro adenotonsillar cell proliferation in children with obstructive sleep apnea. Chest. 2009 May;135(5):1142-1149. doi: 10.1378/chest.08-2102. Epub 2008 Dec 31.
• [7] Cysteinyl leukotrienes induce P-selectin expression in human endothelial cells via a non-CysLT1 receptor-mediated mechanism. J Pharmacol Exp Ther. 1997 May;281(2):655-62.
• [8] Toxicity of human monocytic THP-1 cells and microglia toward SH-SY5Y neuroblastoma cells is reduced by inhibitors of 5-lipoxygenase and its activating protein FLAP. J Leukoc Biol. 2003 Mar;73(3):369-78.
• [9] Expression of functional cysteinyl leukotriene receptors by human basophils. J Allergy Clin Immunol. 2005 Jul;116(1):80-7. doi: 10.1016/j.jaci.2005.03.014.