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
Structure
3D MOL 2D MOL
#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
UNII
1HGW4DR56D
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 Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

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
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

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.