U-0126

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 Search

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

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/11804618 | https://www.ncbi.nlm.nih.gov/pubmed/28560420 | https://www.ncbi.nlm.nih.gov/pubmed/29110347

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

Targets

Primary Target	Pharmacology	Condition	Potency
Dual specificity mitogen-activated protein kinase kinase 1 20 Target ID: CHEMBL3587 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9873633 \| https://www.ncbi.nlm.nih.gov/pubmed/9660836	Inhibitor 8297		72.0 nM [IC50]
Dual specificity mitogen-activated protein kinase kinase 2 9 Target ID: CHEMBL2964 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9660836 \| https://www.ncbi.nlm.nih.gov/pubmed/9873633	Inhibitor 8297		58.0 nM [IC50]

PubMed

Title	Date	PubMed
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	10952721
5-lipoxygenase is phosphorylated by p38 kinase-dependent MAPKAP kinases.	2000 May 9	10779545
Manganese superoxide dismutase signals matrix metalloproteinase expression via H2O2-dependent ERK1/2 activation.	2001 Apr 27	11297530
Arylhydrocarbon receptor (AhR) is involved in negative regulation of adipose differentiation in 3T3-L1 cells: AhR inhibits adipose differentiation independently of dioxin.	2001 Aug	11683414
Transcriptional induction of MKP-1 in response to stress is associated with histone H3 phosphorylation-acetylation.	2001 Dec	11689710
15-Deoxy-delta 12,14-prostaglandin J2 and thiazolidinediones activate the MEK/ERK pathway through phosphatidylinositol 3-kinase in vascular smooth muscle cells.	2001 Dec 28	11687581
Potentiation of cadmium-induced cytotoxicity by sulfur amino acid deprivation through activation of extracellular signal-regulated kinase1/2 (ERK1/2) in conjunction with p38 kinase or c-jun N-terminal kinase (JNK). Complete inhibition of the potentiated toxicity by U0126 an ERK1/2 and p38 kinase inhibitor.	2001 Nov 15	11709198
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	11543732
Early growth-responsive-1-dependent manganese superoxide dismutase gene transcription mediated by platelet-derived growth factor.	2001 Sep	11511524
Nickel requires hypoxia-inducible factor-1 alpha, not redox signaling, to induce plasminogen activator inhibitor-1.	2001 Sep	11504687
Cadmium-induced DNA synthesis and cell proliferation in macrophages: the role of intracellular calcium and signal transduction mechanisms.	2002 Apr	11858940
Indomethacin causes prostaglandin D(2)-like and eotaxin-like selective responses in eosinophils and basophils.	2002 Jul 19	11980903
A novel pathway for nickel-induced interleukin-8 expression.	2002 Jul 5	11978798
IL-17 stimulates inflammatory responses via NF-kappaB and MAP kinase pathways in human colonic myofibroblasts.	2002 Jun	12016129
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	11978788
Inorganic lead activates the mitogen-activated protein kinase kinase-mitogen-activated protein kinase-p90(RSK) signaling pathway in human astrocytoma cells via a protein kinase C-dependent mechanism.	2002 Mar	11861786
Ras/Erk signaling is essential for activation of protein synthesis by Gq protein-coupled receptor agonists in adult cardiomyocytes.	2002 Nov 1	12411397
Up-regulation of c-jun mRNA in cardiac myocytes requires the extracellular signal-regulated kinase cascade, but c-Jun N-terminal kinases are required for efficient up-regulation of c-Jun protein.	2002 Nov 15	12169099
Activation of mitogen-activated protein kinases (MAPKs) by aromatic hydrocarbons: role in the regulation of aryl hydrocarbon receptor (AHR) function.	2002 Sep	12213569
Phosphorylation of extracellular signal-regulated kinase in primary afferent neurons by noxious stimuli and its involvement in peripheral sensitization.	2002 Sep 1	12196597
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	12784042
Tumor promoter arsenite stimulates histone H3 phosphoacetylation of proto-oncogenes c-fos and c-jun chromatin in human diploid fibroblasts.	2003 Apr 11	12547826
Phosphorylation of initiation factor 4E is resistant to SB203580 in cells expressing a drug-resistant mutant of stress-activated protein kinase 2a/p38.	2003 Aug	12781867
Extracellular signaling-regulated kinase-1 and -2 (ERK 1/2) mediate referred hyperalgesia in a murine model of visceral pain.	2003 Aug 19	12941468
Pretreatment with PKC inhibitor triggers TNF-alpha induced apoptosis in TNF-alpha-resistant B16 melanoma BL6 cells.	2003 Dec 26	14654170
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	12446695
Fibroblast growth factor-10 upregulates Na,K-ATPase via the MAPK pathway.	2003 Jun 19	12804770
AhR- and ERK-dependent pathways function synergistically to mediate 2,3,7,8-tetrachlorodibenzo-p-dioxin suppression of peroxisome proliferator-activated receptor-gamma1 expression and subsequent adipocyte differentiation.	2003 May 15	12758056
ERK inhibitor PD98059 enhances docetaxel-induced apoptosis of androgen-independent human prostate cancer cells.	2003 Nov 10	14506750
MAP kinase activation by fluoxetine and its relation to gene expression in cultured rat astrocytes.	2004	15456934
Novel action of activin and bone morphogenetic protein in regulating aldosterone production by human adrenocortical cells.	2004 Feb	14592955
Temporal control of NF-kappaB activation by ERK differentially regulates interleukin-1beta-induced gene expression.	2004 Jan 9	14581482
Short-chain fatty acids enhance nuclear receptor activity through mitogen-activated protein kinase activation and histone deacetylase inhibition.	2004 May 4	15103026
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	15622447
Plasticity in the entorhinal cortex suppresses memory for contextual fear.	2004 Nov 10	15537881
Modulation of the transactivation function of nuclear factor-kappaB by lipopolysaccharide in RAW264.7 macrophages.	2004 Oct	15375559
Asbestos induces tissue factor in Beas-2B cells via PI3 kinase-PKC-mediated signaling.	2004 Oct 8	15371228
Arsenite regulates Cystic Fibrosis Transmembrane Conductance Regulator and P-glycoprotein: evidence of pathway independence.	2005	16121039
Effects of organochlorine insecticides on MAP kinase pathways in human HaCaT keratinocytes: key role of reactive oxygen species.	2005 Aug	15888667
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	16123166
Mesangial cell apoptosis induced by stimulation of the adenosine A3 receptor: signaling and apoptotic events.	2005 Jan	16025880
The effect of a brominated flame retardant, tetrabromobisphenol-A, on free radical formation in human neutrophil granulocytes: the involvement of the MAP kinase pathway and protein kinase C.	2005 Jan	15456914
Investigating the neuroprotective mechanism of action of a CDK5 inhibitor by phosphoproteome analysis.	2005 Jul 1	15838870
7-Ketocholesterol-induced apoptosis. Involvement of several pro-apoptotic but also anti-apoptotic calcium-dependent transduction pathways.	2005 Jun	15955068
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	15757502
Juzentaihoto, a Kampo medicine, enhances IL-12 production by modulating Toll-like receptor 4 signaling pathways in murine peritoneal exudate macrophages.	2005 May	15778123
Decrease in cytosolic phospholipase A2alpha mRNA levels by reactive oxygen species via MAP kinase pathways in PC12 cells: effects of dopaminergic neurotoxins.	2005 May	15683734
Transcriptional profiling of gamma delta T cells identifies a role for vitamin D in the immunoregulation of the V gamma 9V delta 2 response to phosphate-containing ligands.	2005 May 15	15879110
Apoptosis induced by the kinase inhibitor BAY 43-9006 in human leukemia cells involves down-regulation of Mcl-1 through inhibition of translation.	2005 Oct 21	16109713
Role of ERK activation in cisplatin-induced apoptosis in OK renal epithelial cells.	2005 Sep-Oct	16013042

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