Details of the Drug

General Information of Drug (ID: DM31OGF)

Drug Name
U0126
Synonyms
U0126; 109511-58-2; U-0126; U 0126; 1,4-Diamino-2,3-dicyano-1,4-bis(o-aminophenylmercapto)butadiene; UNII-8027P94HLL; CHEBI:64208; 8027P94HLL; (2Z,3Z)-bis{amino[(2-aminophenyl)sulfanyl]methylidene}butanedinitrile; FT-1069-1; 218601-62-8; Succinonitrile, bis(amino(o-aminophenylthio)methylene)-; Butanedinitrile, bis(amino((2-aminophenyl)thio)methylene)-; C18H16N6S2; (2z)-Bis{amino[(2-Aminophenyl)sulfanyl]methylidene}butanedinitrile; (2Z,3Z)-bis{amino[(2-aminophenyl)sulfanyl]methylene}succinonitrile
Indication
Disease Entry ICD 11 Status REF
Discovery agent N.A. Investigative [1]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 380.5
Logarithm of the Partition Coefficient (xlogp) 2
Rotatable Bond Count (rotbonds) 5
Hydrogen Bond Donor Count (hbonddonor) 4
Hydrogen Bond Acceptor Count (hbondacc) 8
Chemical Identifiers
Formula
C18H16N6S2
IUPAC Name
(2Z,3Z)-2,3-bis[amino-(2-aminophenyl)sulfanylmethylidene]butanedinitrile
Canonical SMILES
C1=CC=C(C(=C1)N)S/C(=C(/C(=C(/SC2=CC=CC=C2N)\\N)/C#N)\\C#N)/N
InChI
InChI=1S/C18H16N6S2/c19-9-11(17(23)25-15-7-3-1-5-13(15)21)12(10-20)18(24)26-16-8-4-2-6-14(16)22/h1-8H,21-24H2/b17-11+,18-12+
InChIKey
DVEXZJFMOKTQEZ-JYFOCSDGSA-N
Cross-matching ID
PubChem CID
3006531
ChEBI ID
CHEBI:64208
CAS Number
218601-62-8
TTD ID
D0GD8Y

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
MAPK/ERK kinase kinase 1 (MAP3K1) TTQBCEJ M3K1_HUMAN Inhibitor [2]
MAPK/ERK kinase kinase 2 (MAP3K2) TTK1N5G M3K2_HUMAN Inhibitor [2]
Mitogen-activated protein kinase (MAPK) TTVOE6D NOUNIPROTAC Inhibitor [3]
Mitogen-activated protein kinase kinase (MAPKK) TTCZO0Q NOUNIPROTAC Inhibitor [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]
15-hydroxyprostaglandin dehydrogenase (HPGD) OTYZI6JB PGDH_HUMAN Gene/Protein Processing [6]
72 kDa type IV collagenase (MMP2) OT5NIWA2 MMP2_HUMAN Gene/Protein Processing [7]
Actin, aortic smooth muscle (ACTA2) OTEDLG8E ACTA_HUMAN Gene/Protein Processing [8]
Aldo-keto reductase family 1 member B10 (AKR1B10) OTOA4HTH AK1BA_HUMAN Gene/Protein Processing [9]
Alkaline phosphatase, tissue-nonspecific isozyme (ALPL) OTG7J4BP PPBT_HUMAN Gene/Protein Processing [10]
Amphiregulin (AREG) OTJFOR67 AREG_HUMAN Protein Interaction/Cellular Processes [11]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Gene/Protein Processing [12]
Aromatase (CYP19A1) OTZ6XF74 CP19A_HUMAN Gene/Protein Processing [13]
Aryl hydrocarbon receptor (AHR) OTFE4EYE AHR_HUMAN Protein Interaction/Cellular Processes [14]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

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
MAPK/ERK kinase kinase 1 (MAP3K1) DTT MAP3K1 6.07E-03 -0.28 -0.52
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: 5282).
2 Pharmacological inhibitors of MAPK pathways. Trends Pharmacol Sci. 2002 Jan;23(1):40-5.
3 Intravenous administration of MEK inhibitor U0126 affords brain protection against forebrain ischemia and focal cerebral ischemia. Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11569-74.
4 Transcriptional regulation of basal cyclooxygenase-2 expression in murine lung tumor-derived cell lines by CCAAT/enhancer-binding protein and activating transcription factor/cAMP response element-binding protein. Mol Pharmacol. 2002 Aug;62(2):326-33.
5 The ERK1/2 signaling pathway regulates 11beta-hydroxysteroid dehydrogenase type 2 expression in human trophoblast cells through a transcriptional mechanism. Biol Reprod. 2013 Oct 17;89(4):92.
6 15-Hydroxyprostaglandin dehydrogenase (15-PGDH) is up-regulated by flurbiprofen and other non-steroidal anti-inflammatory drugs in human colon cancer HT29 cells. Arch Biochem Biophys. 2009 Jul 15;487(2):139-45. doi: 10.1016/j.abb.2009.05.017. Epub 2009 Jun 6.
7 Tomatidine inhibits invasion of human lung adenocarcinoma cell A549 by reducing matrix metalloproteinases expression. Chem Biol Interact. 2013 May 25;203(3):580-7. doi: 10.1016/j.cbi.2013.03.016. Epub 2013 Apr 6.
8 Synergistic action of the nephrotoxic mycotoxins ochratoxin A and citrinin at nanomolar concentrations in human proximal tubule-derived cells. Toxicol Lett. 2018 Jul;291:149-157. doi: 10.1016/j.toxlet.2018.04.014. Epub 2018 Apr 17.
9 Chrysin enhances sensitivity of BEL-7402/ADM cells to doxorubicin by suppressing PI3K/Akt/Nrf2 and ERK/Nrf2 pathway. Chem Biol Interact. 2013 Oct 25;206(1):100-8.
10 Pharmacological inhibition of protein kinase D suppresses epithelial ovarian cancer via MAPK/ERK1/2/Runx2 signalling axis. Cell Signal. 2023 Oct;110:110849. doi: 10.1016/j.cellsig.2023.110849. Epub 2023 Aug 8.
11 Src family kinase inhibitors block amphiregulin-mediated autocrine ErbB signaling in normal human keratinocytes. Mol Pharmacol. 2005 Apr;67(4):1145-57. doi: 10.1124/mol.104.004689. Epub 2004 Dec 22.
12 The novel dual PI3K/mTOR inhibitor GDC-0941 synergizes with the MEK inhibitor U0126 in non-small cell lung cancer cells. Mol Med Rep. 2012 Feb;5(2):503-8. doi: 10.3892/mmr.2011.682. Epub 2011 Nov 16.
13 Low-dose bisphenol A activates the ERK signaling pathway and attenuates steroidogenic gene expression in human placental cells. Biol Reprod. 2018 Feb 1;98(2):250-258.
14 ERK kinase inhibition stabilizes the aryl hydrocarbon receptor: implications for transcriptional activation and protein degradation. J Biol Chem. 2005 Feb 11;280(6):4350-9.