U0126

U0126 is a highly selective inhibitor of both MEK1 and MEK2, a type of MAPK/ERK kinase.[1][2] 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 by simultaneously blocking both extracellular signal-regulated kinase (ERK) and mammalian target of rapamycin (mTOR)-p70(S6K) pathways.[3] 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.[4] 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
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
ChEBI
ChEMBL
Chemical and physical data
FormulaC18H16N6S2
Molar mass380.49 g·mol−1
3D model (JSmol)
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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 at New York University.[5]

See also

References

  1. Favata, M., et al., Identification of a novel inhibitor of mitogen-activated protein kinase. J. Biol. Chem. 273, 18623, (1998)
  2. DeSilva, D., et al., Inhibition of mitogen-activated protein kinase blocks T cell proliferation but does not induce or prevent anergy. J. Immunol. 160, 4175, (1998)
  3. Duncia, J.V., et al., MEK inhibitors: The chemistry and biological activity of U0126, its analogs, and cyclization products. Bioorg. Med. Chem. Lett. 8, 2839-2844, (1998)
  4. Fukazawa, H., et al., Mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) inhibitors restore anoikis sensitivity in human breast cancer cell lines with a constitutively activated extracellular-regulated kinase (ERK) pathway. Mol. Cancer Ther., 303-309, (2002)
  5. Smith, Kerri (2007-03-11). "Wipe out a single memory". Nature Magazine. Retrieved 2017-12-31.
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