U0126 is a highly selective inhibitor of both

MEK1 Dual specificity mitogen-activated protein kinase kinase 1 is an enzyme that in humans is encoded by the ''MAP2K1'' gene. Function The protein encoded by this gene is a member of the dual-specificity protein kinase family that acts as a mito ...

and

MEK2 Dual specificity mitogen-activated protein kinase kinase 2 is an enzyme that in humans is encoded by the ''MAP2K2'' gene. It is more commonly known as MEK2, but has many alternative names including CFC4, MKK2, MAPKK2 and PRKMK2. Function The ...

, a type of MAPK/ERK kinase. U0126 was found to functionally antagonize AP-1 transcriptional activity via noncompetitive inhibition of the dual specificity kinase MEK with IC₅₀ of 72 nM for MEK1 and 58 nM for MEK2. U0126 inhibited anchorage-independent growth of Ki-ras-transformed rat

fibroblasts A fibroblast is a type of biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework ( stroma) for animal tissues, and plays a critical role in wound healing. Fibroblasts are the most common cells ...

by simultaneously blocking both extracellular signal-regulated kinase (ERK) and mammalian target of rapamycin (mTOR)-p70(S6K) pathways. The effects of U0126 on the growth of eight human breast cancer cell lines shown that U0126 selectively repressed anchorage-independent growth of MDA-MB231 and HBC4 cells, two lines with constitutively activated ERK. Loss of contact with substratum triggers apoptosis in many normal cell types, a phenomenon termed anoikis. U0126 sensitized MDA-MB231 and HBC4 to anoikis, i.e., upon treatment with U0126, cells deprived of anchorage entered apoptosis. U0126 is also a weak inhibitor of PKC, Raf, ERK, JNK, MEKK, MKK-3, MKK-4/SEK, MKK-6, Cdk2 and Cdk4. Its potential for wiping long-term memories in rats has been studied at the

Center for Neural Science Center or centre may refer to: Mathematics *Center (geometry), the middle of an object * Center (algebra), used in various contexts ** Center (group theory) ** Center (ring theory) * Graph center, the set of all vertices of minimum eccentricit ...

at New York University.

References

{{reflist Protein kinase inhibitors Nitriles Anilines

See also

References