Details of the Drug

General Information of Drug (ID: DME26RS)

• Drug Name: LTB4
• Synonyms: Leukotriene B4; LEUKOTRIENE B4; 5,12-Dihete; 71160-24-2; 5,12-Hete; UNII-1HGW4DR56D; (5S,6Z,8E,10E,12R,14Z)-5,12-dihydroxyicosa-6,8,10,14-tetraenoic acid; 1HGW4DR56D; CHEMBL65061; 5S,12R-dihydroxy-6Z,8E,10E,14Z-eicosatetraenoic acid; CHEBI:15647; VNYSSYRCGWBHLG-AMOLWHMGSA-N; [5S,12R]-Dihydroxy-[6Z,8E,10E,14Z]-eicosatetraenoic acid; Leukotriene B; 5(S),12(R)-Dihydroxy-6-cis-8-trans-10-trans-14-cis-eicosatetraenoic Acid; (S-(R*,S*-(E,Z,E,Z)))-5,12-Dihydroxy-6,8,10,14-eicosatetraenoic acid; 6,8,10,14-Eicosatetraenoic acid,; Leukotriene B4 agonist (HIV infection), LTB4 Sweden AB; LEUKOTRIENE_B4

Indication

Disease Entry	ICD 11	Status	REF
Human immunodeficiency virus infection	1C62	Phase 2	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 1:
  Molecular Weight (mw); 336.5
  Logarithm of the Partition Coefficient (xlogp); 4.1
  Rotatable Bond Count (rotbonds); 14
  Hydrogen Bond Donor Count (hbonddonor); 3
  Hydrogen Bond Acceptor Count (hbondacc); 4
• Chemical Identifiers:
  Formula: C20H32O4
  IUPAC Name: (5S,6Z,8E,10E,12R,14Z)-5,12-dihydroxyicosa-6,8,10,14-tetraenoic acid
  Canonical SMILES: CCCCC/C=C\\C[C@H](/C=C/C=C/C=C\\[C@H](CCCC(=O)O)O)O
  InChI: InChI=1S/C20H32O4/c1-2-3-4-5-6-9-13-18(21)14-10-7-8-11-15-19(22)16-12-17-20(23)24/h6-11,14-15,18-19,21-22H,2-5,12-13,16-17H2,1H3,(H,23,24)/b8-7+,9-6-,14-10+,15-11-/t18-,19-/m1/s1
  InChIKey: VNYSSYRCGWBHLG-AMOLWHMGSA-N
• Cross-matching ID:
  PubChem CID: 5280492
  ChEBI ID: CHEBI:15647
  CAS Number: 71160-24-2
  DrugBank ID: DB12961
  TTD ID: D0O4NR
  INTEDE ID: DR1851

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Leukotriene B4 receptor 1 (LTB4R)	TTN53ZF	LT4R1_HUMAN	Agonist	[2]
Leukotriene B4 receptor 2 (LTB4R2)	TTVJX54	LT4R2_HUMAN	Inhibitor	[3]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Leukotriene B4 omega-hydroxylase (CYP4F3) Main DME	DEFCMPI	CP4F3_HUMAN	Substrate	[4]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2)	OTHF4H9U	DHI2_HUMAN	Gene/Protein Processing	[5]
Actin, aortic smooth muscle (ACTA2)	OTEDLG8E	ACTA_HUMAN	Gene/Protein Processing	[6]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Gene/Protein Processing	[7]
Complement C5 (C5)	OTSL3OIC	CO5_HUMAN	Regulation of Drug Effects	[8]
Granulocyte-macrophage colony-stimulating factor (CSF2)	OT1M7D28	CSF2_HUMAN	Protein Interaction/Cellular Processes	[9]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1)	OT2YYI1A	MCL1_HUMAN	Gene/Protein Processing	[7]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Regulation of Drug Effects	[10]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Gene/Protein Processing	[11]
Leukotriene A-4 hydrolase (LTA4H)	OTWSZ0QT	LKHA4_HUMAN	Biotransformations	[12]
Leukotriene B4 receptor 2 (LTB4R2)	OTYRQR2T	LT4R2_HUMAN	Protein Interaction/Cellular Processes	[13]

Molecular Expression Atlas of This Drug

• The Studied Disease: Human immunodeficiency virus infection
• ICD Disease Classification: 1C62

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Leukotriene B4 receptor 1 (LTB4R)	DTT	LTB4R	3.40E-01	0.21	0.53
Leukotriene B4 omega-hydroxylase (CYP4F3)	DME	CYP4F3	1.08E-02	-3.54E+00	-1.59E+00

References

• [1] ClinicalTrials.gov (NCT00251537) A Pilot Study of LTB4 in HIV-1 Infected Adults in LTB4 Sweden AB.
• [2] LTB4 promotes insulin resistance in obese mice by acting on macrophages, hepatocytes and myocytes. Nat Med. 2015 Mar;21(3):239-47.
• [3] Diaryl ether/carboxylic acid derivatives of LY255283: Receptor antagonists of leukotriene B4, Bioorg. Med. Chem. Lett. 3(10):1985-1990 (1993).
• [4] Leukotriene B4: metabolism and signal transduction. Arch Biochem Biophys. 2001 Jan 15;385(2):231-41.
• [5] Effect of the interaction between lipoxygenase pathway and progesterone on the regulation of hydroxysteroid 11-Beta dehydrogenase 2 in cultured human term placental trophoblasts. Biol Reprod. 2008 Mar;78(3):514-20.
• [6] Aryl hydrocarbon receptor-ligand axis mediates pulmonary fibroblast migration and differentiation through increased arachidonic acid metabolism. Toxicology. 2016 Aug 31;370:116-126.
• [7] The anti-apoptotic effect of leukotriene B4 in neutrophils: a role for phosphatidylinositol 3-kinase, extracellular signal-regulated kinase and Mcl-1. Cell Signal. 2006 Apr;18(4):479-87. doi: 10.1016/j.cellsig.2005.05.021. Epub 2005 Jun 20.
• [8] Role of 5-lipoxygenase products in the local accumulation of neutrophils in dermal inflammation in the rabbit. J Immunol. 1999 Sep 15;163(6):3449-58.
• [9] 5-oxo-6,8,11,14-eicosatetraenoic acid stimulates the release of the eosinophil survival factor granulocyte/macrophage colony-stimulating factor from monocytes. J Biol Chem. 2004 Jul 2;279(27):28159-64. doi: 10.1074/jbc.M401537200. Epub 2004 May 10.
• [10] The antioxidant resveratrol protects against chondrocyte apoptosis via effects on mitochondrial polarization and ATP production. Arthritis Rheum. 2008 Sep;58(9):2786-97. doi: 10.1002/art.23799.
• [11] Leukotriene B4 mediates histamine induction of NF-kappaB and IL-8 in human bronchial epithelial cells. Am J Physiol. 1998 Jun;274(6):L1030-9.
• [12] Anti-inflammatory activity of a potent, selective leukotriene A4 hydrolase inhibitor in comparison with the 5-lipoxygenase inhibitor zileuton. J Pharmacol Exp Ther. 2007 Jun;321(3):1154-60. doi: 10.1124/jpet.106.115436. Epub 2007 Mar 19.
• [13] A novel hepatointestinal leukotriene B4 receptor. Cloning and functional characterization. J Biol Chem. 2000 Dec 29;275(52):40686-94. doi: 10.1074/jbc.M004512200.