Details of the Drug

General Information of Drug (ID: DMT0O7H)

Drug Name
MK-886
Synonyms
MK-886; 118414-82-7; MK 886; MK886; 3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-isopropyl-1H-indol-2-yl)-2,2-dimethylpropanoic acid; UNII-080626SQ8C; QAOAOVKBIIKRNL-UHFFFAOYSA-N; L-663,536; CHEMBL29097; CHEBI:75390; L 663536; MK-886 (L-663,536); 080626SQ8C; 3-[3-tert-butylsulfanyl-1-[(4-chlorophenyl)methyl]-5-propan-2-ylindol-2-yl]-2,2-dimethylpropanoic acid; 1H-Indole-2-propanoic acid, 1-[(4-chlorophenyl)methyl]-3-[(1,1-dimethylethyl)thio]-Alpha,Alpha-dimethyl-5-(1-methylethyl)- [CAS]; L-663536; SMR000466278
Indication
Disease Entry ICD 11 Status REF
Asthma CA23 Discontinued in Phase 2 [1]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 1 Molecular Weight (mw) 472.1
Logarithm of the Partition Coefficient (xlogp) 7.6
Rotatable Bond Count (rotbonds) 8
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 3
Chemical Identifiers
Formula
C27H34ClNO2S
IUPAC Name
3-[3-tert-butylsulfanyl-1-[(4-chlorophenyl)methyl]-5-propan-2-ylindol-2-yl]-2,2-dimethylpropanoic acid
Canonical SMILES
CC(C)C1=CC2=C(C=C1)N(C(=C2SC(C)(C)C)CC(C)(C)C(=O)O)CC3=CC=C(C=C3)Cl
InChI
InChI=1S/C27H34ClNO2S/c1-17(2)19-10-13-22-21(14-19)24(32-26(3,4)5)23(15-27(6,7)25(30)31)29(22)16-18-8-11-20(28)12-9-18/h8-14,17H,15-16H2,1-7H3,(H,30,31)
InChIKey
QAOAOVKBIIKRNL-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
3651377
ChEBI ID
CHEBI:75390
CAS Number
118414-82-7
DrugBank ID
DB16739
TTD ID
D0K2ER

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Arachidonate 5-lipoxygenase (5-LOX) TT2J34L LOX5_HUMAN Modulator [2]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Apolipoprotein A-I (APOA1) OT5THARI APOA1_HUMAN Gene/Protein Processing [3]
Arachidonate 5-lipoxygenase-activating protein (ALOX5AP) OT0DH40W AL5AP_HUMAN Gene/Protein Processing [4]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Gene/Protein Processing [5]
DNA polymerase iota (POLI) OTBA4DCE POLI_HUMAN Gene/Protein Processing [6]
DNA polymerase kappa (POLK) OTKZ38JH POLK_HUMAN Gene/Protein Processing [6]
DNA-directed DNA/RNA polymerase mu (POLM) OT0SRIP4 DPOLM_HUMAN Gene/Protein Processing [6]
Peroxisome proliferator-activated receptor alpha (PPARA) OTK095PP PPARA_HUMAN Gene/Protein Processing [7]
Peroxisome proliferator-activated receptor gamma (PPARG) OTHMARHO PPARG_HUMAN Gene/Protein Processing [7]
Prostaglandin E synthase (PTGES) OTB7YQFU PTGES_HUMAN Gene/Protein Processing [8]
Retinoic acid receptor RXR-alpha (RXRA) OTP1TBDM RXRA_HUMAN Gene/Protein Processing [7]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Asthma
ICD Disease Classification CA23
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Arachidonate 5-lipoxygenase (5-LOX) DTT ALOX5 4.15E-01 -0.06 -0.15
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

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: 2655).
2 Inhibitory effects of MK-886 on arachidonic acid metabolism in human phagocytes. Br J Pharmacol. 1990 May;100(1):15-20.
3 Role of the nuclear receptors HNF4 alpha, PPAR alpha, and LXRs in the TNF alpha-mediated inhibition of human apolipoprotein A-I gene expression in HepG2 cells. Biochemistry. 2009 Dec 22;48(50):11950-60. doi: 10.1021/bi9015742.
4 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.
5 The role of transient receptor potential channel blockers in human gastric cancer cell viability. Can J Physiol Pharmacol. 2012 Feb;90(2):175-86. doi: 10.1139/y11-114. Epub 2012 Feb 6.
6 Leukotriene biosynthesis inhibitor MK886 impedes DNA polymerase activity. Chem Res Toxicol. 2013 Feb 18;26(2):221-32. doi: 10.1021/tx300392m. Epub 2013 Jan 31.
7 Inhibitors of the arachidonic acid pathway and peroxisome proliferator-activated receptor ligands have superadditive effects on lung cancer growth inhibition. Cancer Res. 2005 May 15;65(10):4181-90. doi: 10.1158/0008-5472.CAN-04-3441.
8 Arzanol, a prenylated heterodimeric phloroglucinyl pyrone, inhibits eicosanoid biosynthesis and exhibits anti-inflammatory efficacy in vivo. Biochem Pharmacol. 2011 Jan 15;81(2):259-68.