U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C18H16N6S2
Molecular Weight 380.49
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 2
Charge 0

SHOW SMILES / InChI
Structure of U-0126

SMILES

N\C(SC1=CC=CC=C1N)=C(C#N)/C(C#N)=C(\N)SC2=C(N)C=CC=C2

InChI

InChIKey=DVEXZJFMOKTQEZ-JYFOCSDGSA-N
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+

HIDE SMILES / InChI

Molecular Formula C18H16N6S2
Molecular Weight 380.49
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 2
Optical Activity NONE

U0126 is a highly selective inhibitor of both MEK1 and MEK2, a type of MAPK/ERK kinase. The inhibitory effects of U0126 on MEK and ERK activation have been confirmed repeatedly, and treatments with U0126 have been shown to inhibit proliferation and migration of cancer cells in vivo and in vitro. U0126 has been widely used as an inhibitor for the Ras/Raf/MEK/ERK signaling pathway. U0126 treatments lead to cancer cell death, which agrees with the well-known role of the Ras/Raf/MEK/ERK pathway in supporting cell survival. U0126 enhances apoptosis in human breast cancer MCF-7 cells, acute myeloid leukemia, and PC12 cells.

Approval Year

PubMed

PubMed

TitleDatePubMed
Residual type 1 immunity in patients genetically deficient for interleukin 12 receptor beta1 (IL-12Rbeta1): evidence for an IL-12Rbeta1-independent pathway of IL-12 responsiveness in human T cells.
2000 Aug 21
Manganese superoxide dismutase signals matrix metalloproteinase expression via H2O2-dependent ERK1/2 activation.
2001 Apr 27
Arylhydrocarbon receptor (AhR) is involved in negative regulation of adipose differentiation in 3T3-L1 cells: AhR inhibits adipose differentiation independently of dioxin.
2001 Aug
Transcriptional induction of MKP-1 in response to stress is associated with histone H3 phosphorylation-acetylation.
2001 Dec
Effects of Ginkgo biloba extract (EGb 761) and quercetin on lipopolysaccharide-induced signaling pathways involved in the release of tumor necrosis factor-alpha.
2001 Oct 1
Early growth-responsive-1-dependent manganese superoxide dismutase gene transcription mediated by platelet-derived growth factor.
2001 Sep
IL-17 stimulates inflammatory responses via NF-kappaB and MAP kinase pathways in human colonic myofibroblasts.
2002 Jun
Activation of the ERK pathway and atypical protein kinase C isoforms in exercise- and aminoimidazole-4-carboxamide-1-beta-D-riboside (AICAR)-stimulated glucose transport.
2002 Jun 28
Induction of early growth response gene Egr2 by basic calcium phosphate crystals through a calcium-dependent protein kinase C-independent p44/42 mitogen-activated protein kinase pathway.
2003
Tumor promoter arsenite stimulates histone H3 phosphoacetylation of proto-oncogenes c-fos and c-jun chromatin in human diploid fibroblasts.
2003 Apr 11
Activation of mitogen-activated protein kinase pathway by keratinocyte growth factor or fibroblast growth factor-10 promotes cell proliferation in human endometrial carcinoma cells.
2003 Feb
Sulindac sulfide inhibits epidermal growth factor-induced phosphorylation of extracellular-regulated kinase 1/2 and Bad in human colon cancer cells.
2003 Feb 1
Increased protein stability as a mechanism that enhances Nrf2-mediated transcriptional activation of the antioxidant response element. Degradation of Nrf2 by the 26 S proteasome.
2003 Feb 14
Fibroblast growth factor-10 upregulates Na,K-ATPase via the MAPK pathway.
2003 Jun 19
MAP kinase-dependent induction of clock gene expression by alpha 1-adrenergic receptor activation.
2003 May 8
ERK inhibitor PD98059 enhances docetaxel-induced apoptosis of androgen-independent human prostate cancer cells.
2003 Nov 10
Involvement of ERK1/2 and p38 MAP kinase in doxorubicin-induced uPA expression in human RC-K8 lymphoma and NCI-H69 small cell lung carcinoma cells.
2004
Involvement of extracellular signal-regulated kinase/mitogen-activated protein kinase pathway in multidrug resistance induced by HBx in hepatoma cell line.
2004 Dec 1
Extracellular zinc triggers ERK-dependent activation of Na+/H+ exchange in colonocytes mediated by the zinc-sensing receptor.
2004 Dec 10
Differentiation-inducing factor-1-induced growth arrest of K562 leukemia cells involves the reduction of ERK1/2 activity.
2004 Feb 6
12-O-tetradecanoylphorbol-13-acetate may both potentiate and decrease the generation of apoptosis by the antileukemic agent arsenic trioxide in human promonocytic cells. Regulation by extracellular signal-regulated protein kinases and glutathione.
2004 Jan 30
Short-chain fatty acids enhance nuclear receptor activity through mitogen-activated protein kinase activation and histone deacetylase inhibition.
2004 May 4
Hyperforin, the active component of St. John's wort, induces IL-8 expression in human intestinal epithelial cells via a MAPK-dependent, NF-kappaB-independent pathway.
2004 Nov
Roles of mitogen activated protein kinases and EGF receptor in arsenite-stimulated matrix metalloproteinase-9 production.
2004 Nov 1
Plasticity in the entorhinal cortex suppresses memory for contextual fear.
2004 Nov 10
Extracellular signal-regulated kinase activation and Bcl-2 downregulation mediate apoptosis after gemcitabine treatment partly via a p53-independent pathway.
2004 Oct 19
Arsenite regulates Cystic Fibrosis Transmembrane Conductance Regulator and P-glycoprotein: evidence of pathway independence.
2005
Effects of organochlorine insecticides on MAP kinase pathways in human HaCaT keratinocytes: key role of reactive oxygen species.
2005 Aug
Ontogeny of rapid estrogen-mediated extracellular signal-regulated kinase signaling in the rat cerebellar cortex: potent nongenomic agonist and endocrine disrupting activity of the xenoestrogen bisphenol A.
2005 Dec
Role of cell signaling in B[a]P-induced apoptosis: characterization of unspecific effects of cell signaling inhibitors and apoptotic effects of B[a]P metabolites.
2005 Jan 15
Pharmacologic inhibition of RAF-->MEK-->ERK signaling elicits pancreatic cancer cell cycle arrest through induced expression of p27Kip1.
2005 Jun 1
Activation of protein synthesis in cardiomyocytes by the hypertrophic agent phenylephrine requires the activation of ERK and involves phosphorylation of tuberous sclerosis complex 2 (TSC2).
2005 Jun 15
Transfected beta3- but not beta2-adrenergic receptors regulate cystic fibrosis transmembrane conductance regulator activity via a new pathway involving the mitogen-activated protein kinases extracellular signal-regulated kinases.
2005 Mar
Decrease in cytosolic phospholipase A2alpha mRNA levels by reactive oxygen species via MAP kinase pathways in PC12 cells: effects of dopaminergic neurotoxins.
2005 May
Histamine H4 receptor stimulation suppresses IL-12p70 production and mediates chemotaxis in human monocyte-derived dendritic cells.
2005 May 1
Role of ERK activation in cisplatin-induced apoptosis in OK renal epithelial cells.
2005 Sep-Oct
Activation of ERK1/2 and p38 kinases by polycyclic aromatic hydrocarbons in rat liver epithelial cells is associated with induction of apoptosis.
2006 Mar 15
Substance Class Chemical
Created
by admin
on Sat Dec 16 09:05:06 GMT 2023
Edited
by admin
on Sat Dec 16 09:05:06 GMT 2023
Record UNII
8027P94HLL
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
U-0126
Code English
U0126
Code English
FT-1069-1
Code English
1,4-DIAMINO-2,3-DICYANO-1,4-BIS(2-AMINOPHENYLTHIO)BUTADIENE
Common Name English
BUTANEDINITRILE, BIS(AMINO((2-AMINOPHENYL)THIO)METHYLENE)-, (2Z,3Z)-
Systematic Name English
Classification Tree Code System Code
NCI_THESAURUS C2149
Created by admin on Sat Dec 16 09:05:07 GMT 2023 , Edited by admin on Sat Dec 16 09:05:07 GMT 2023
FDA ORPHAN DRUG 593217
Created by admin on Sat Dec 16 09:05:07 GMT 2023 , Edited by admin on Sat Dec 16 09:05:07 GMT 2023
EU-Orphan Drug EU/3/17/1935
Created by admin on Sat Dec 16 09:05:07 GMT 2023 , Edited by admin on Sat Dec 16 09:05:07 GMT 2023
Code System Code Type Description
PUBCHEM
3006531
Created by admin on Sat Dec 16 09:05:07 GMT 2023 , Edited by admin on Sat Dec 16 09:05:07 GMT 2023
PRIMARY
FDA UNII
8027P94HLL
Created by admin on Sat Dec 16 09:05:07 GMT 2023 , Edited by admin on Sat Dec 16 09:05:07 GMT 2023
PRIMARY
CAS
109511-58-2
Created by admin on Sat Dec 16 09:05:07 GMT 2023 , Edited by admin on Sat Dec 16 09:05:07 GMT 2023
NON-SPECIFIC STEREOCHEMISTRY
EPA CompTox
DTXSID4040470
Created by admin on Sat Dec 16 09:05:07 GMT 2023 , Edited by admin on Sat Dec 16 09:05:07 GMT 2023
PRIMARY
EVMPD
SUB192758
Created by admin on Sat Dec 16 09:05:07 GMT 2023 , Edited by admin on Sat Dec 16 09:05:07 GMT 2023
PRIMARY
SMS_ID
100000177388
Created by admin on Sat Dec 16 09:05:07 GMT 2023 , Edited by admin on Sat Dec 16 09:05:07 GMT 2023
PRIMARY
NCI_THESAURUS
C1825
Created by admin on Sat Dec 16 09:05:07 GMT 2023 , Edited by admin on Sat Dec 16 09:05:07 GMT 2023
PRIMARY
CHEBI
90693
Created by admin on Sat Dec 16 09:05:07 GMT 2023 , Edited by admin on Sat Dec 16 09:05:07 GMT 2023
PRIMARY
WIKIPEDIA
U0126
Created by admin on Sat Dec 16 09:05:07 GMT 2023 , Edited by admin on Sat Dec 16 09:05:07 GMT 2023
PRIMARY
CAS
218601-62-8
Created by admin on Sat Dec 16 09:05:07 GMT 2023 , Edited by admin on Sat Dec 16 09:05:07 GMT 2023
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
IC50
TARGET -> INHIBITOR
IC50
Related Record Type Details
ACTIVE MOIETY