U0126-EtOH

U0126-EtOH is a highly selective inhibitor of MEK1/2 with IC50 of 0.07 μM/0.06 μM, 100-fold higher affinity for ΔN3-S218E/S222D MEK than PD98059. This inhibition of MEK1/2 is noncompetitive with ERK and ATP.

Product information

CAS Number: 1173097-76-1

Molecular Weight: 426.56

Formula: C20H22N6OS2

Chemical Name: bis({amino[(2-aminophenyl)sulfanyl]methylidene})butanedinitrile; ethanol

Smiles: CCO.NC1=CC=CC=C1SC(N)=C(C#N)C(C#N)=C(N)SC1=CC=CC=C1N

InChiKey: CFQULUVMLGZVAF-OYJDLGDISA-N

InChi: InChI=1S/C18H16N6S2.C2H6O/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;1-2-3/h1-8H,21-24H2;3H,2H2,1H3/b17-11+,18-12+;

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO: ≥ 49 mg/mL

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥360 days if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

Treatment with U0126 efficiently reduces progeny virus titers of all tested strains in A549 cells. While nM concentrations of U0126 are efficient to reduce H1N1v and H5N1 (MB1), μM concentrations of U0126 are required to reduce the virus titer of H5N1 (GSB) and H7N7. The EC50 values for U0126 against H1N1v are 1.2±0.4 μM in A549 cells and 74.7±1.0 μM in MDCKII cells.Rat hepatocarcinoma cells (FAO) stimulated by fetal calf serum (FCS) exhibits a significant proportion in S phase (32.62%) whereas U0126 strongly decreases the proportion of cells in S phase (9.92%) and increases the proportion of cells in G0-G1 phase and to a lesser extent in G2/M.

In Vivo:

Mice are treated daily with U0126 (i.p., 10.5 mg/kg). In control experiment, tumor sizes are constant or slightly increase all over the kinetic. At the opposite, in all U0126 experiments, engraftment and early tumor growth are significantly decreased. Furthermore, a 60-70% reduction in the volume of tumors treated with U0126 is obtained 9 days after injection and thereafter. Rats are subjected to 120?minutes transient middle cerebral artery occlusion (tMCAO) and thereafter treated with the U0126 (i.p., 30 mg/kg) at 0 and 24 hours of reperfusion. After treatment with U0126, the vasoconstriction to S6c is markedly reduced.

References:

1. Duncia JV, et al. MEK inhibitors: the chemistry and biological activity of U0126, its analogs, and cyclization products. Bioorg Med Chem Lett. 1998, 8(20), 2839-2844.
2. Droebner K, et al. Antiviral activity of the MEK-inhibitor U0126 against pandemic H1N1v and highly pathogenic avian influenza virus in vitro and in vivo. Antiviral Res. 2011, 92(2), 195-203.
3. Bessard A, et al. RNAi-mediated ERK2 knockdown inhibits growth of tumor cells in vitro and in vivo. Oncogene. 2008 Sep 11;27(40):5315-25.
4. Ahnstedt H, et al. U0126 attenuates cerebral vasoconstriction and improves long-term neurologic outcome after stroke in female rats. J Cereb Blood Flow Metab. 2015 Mar;35(3):454-60.

Products are for research use only. Not for human use.