U0126

U0126 Property

Melting point:

approximate 154℃(dec.)

Boiling point:

565.1±50.0 °C(Predicted)

Density 

1.44

RTECS 

EJ9710000

storage temp. 

Desiccate at +4°C

solubility 

Soluble in DMSO (up to 200 mg/ml).

pka

2.11±0.10(Predicted)

form 

White solid

color 

White

Water Solubility 

Soluble in DMSO. Poorly soluble in ethanol and water

Stability:

Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 3 months.

Safety

HS Code 

2930909899

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P304+P340IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

P405Store locked up.

U0126 Chemical Properties,Usage,Production

Description

U-0126 is a MEK inhibitor with IC₅₀ values of 72 nM and 58 nM for MEK1 and MEK2, respectively. It is noncompetitive with respect adenosine triphosphate (ATP) and its phosphorylation target ERK and it shows little to no inhibition against a number of other kinases including PKC, Ab1, Raf, MEKK, ERK, JNK, MKK-3, MKK-4, MKK-6, Cdk2, and Cdk4. However, U-0126 does phosphorylate and activate AMP-activated protein kinase (AMPK) in a dose-dependent manner (EC₅₀ = 15 μM in HEK293 cells). It increases the ratios of ADP to ATP and AMP to ATP and increases phosphorylation of the AMPK target acetyl-CoA carboxylase (ACC).

Uses

A chemically synthesized and highly selective inhibitor of both MEK1 and MEK2 with IC50s of 70 nM and 60 nM, respectively.

Uses

U0126 is a MEK inhibitor.

Definition

ChEBI: A dinitrile that is succinonitrile in which the methylene hydrogens at positions 2 and 3 are substituted by (2-aminophenyl)sulfanyl]methylidene groups. A potent and selective non-competitive inhibitor of MAP kinase kinase.

General Description

A potent and specific inhibitor of MEK1 (IC₅₀ = 72 nM) and MEK2 (IC₅₀ = 58 nM). The inhibition is noncompetitive with respect to MEK substrates, ATP and ERK. Has very little effect on other kinases, such as Abl, Cdk2, Cdk4, ERK, JNK, MEKK, MKK-3, MKK-4/SEK, MKK-6, PKC, and Raf. Shown to block doxazosin-induced osteoblastic differentiation. U0126 also acts as an immunosuppressant by effectively blocking IL-2 synthesis and T cell proliferation without affecting the long-term outcomes of either T cell activation or tolerance. Noncompetitive with respect to ATP. Also available in InSolution format (Cat. No. 662009.

Biological Activity

Potent and selective non-competitive inhibitor of MAP kinase kinase. Inhibits MEK-1 and MEK-2 (IC 50 values of 0.07 and 0.06 μ M respectively) with little or no effect on the activities of PKC, Abl, Raf, MEKK, ERK, JNK, MKK-3, MKK-4/SEK, MKK-6, Cdk2 or Cdk4. Centrally active following systemic administration in vivo . Also available as part of the MAPK Cascade Inhibitor Tocriset™ and MAPK Inhibitor Tocriset™ .

Biochem/physiol Actions

Primary TargetMEK1 and MEK2

storage

+4°C (desiccate)

References

[1] M F FAVATA. Identification of a novel inhibitor of mitogen-activated protein kinase kinase.[J]. The Journal of Biological Chemistry, 1998, 273 29: 18623-18632. DOI:10.1074/jbc.273.29.18623
[2] SEIGO MIYOSHI. Antitumor activity of MEK and PI3K inhibitors against malignant pleural mesothelioma cells in vitro and in vivo.[J]. International journal of oncology, 2012, 41 2: 449-456. DOI:10.3892/ijo.2012.1462
[3] KATIE L. PRICOLA. Interleukin-6 maintains bone marrow-derived mesenchymal stem cell stemness by an ERK1/2-dependent mechanism†‡[J]. Journal of cellular biochemistry, 2009, 108 3: 577-588. DOI:10.1002/jcb.22289