U0126
U0126
Molecule
U0126[1][2] is the 'code' name for a compound associated with cancer treatment[3] and also in preventing ischemia and cellular oxidative stress. It also has likely utility in strokes and heart attacks.[4] This compound is available for research purposes from a number of companies.[5][6]
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The specific compound is not approved by the FDA as a therapeutic agent, though it has been used in medical settings.[7] Members of this broad class of chemical compounds have been approved by the US FDA for the treatment of specific cancers.[8][9]
It is a highly selective inhibitor of both MEK1 and MEK2, a type of MAPK/ERK kinase.[10][11] 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.[12]
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.[13] 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.[14]
Its potential for wiping long-term memories in rats has been studied at the Center for Neural Science at New York University.[15]