Application | Comment | Organism |
---|---|---|
drug development | because of their importance in cell proliferation and signaling, MAPK pathways are being targeted for drugs for oncology, inflammation and other conditions. MEK inhibitors may be beneficial for cancer therapy. MEK inhibition is likely to be of particular importance in specific tumors where the MEK pathway is highly and directly activated | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
AS-703026 | a MEK12 inhibitor, binds in the allosteric site of MEK1. For A-375 cells, AS-703026 has a growth IC50 of 4 nM | Homo sapiens | |
AZD8330 | ARRY424704, renamed AZD8330 | Homo sapiens | |
BAY 869766 | i.e. RDEA119 | Homo sapiens | |
capecitabine | - |
Homo sapiens | |
CH-4987655/RO4987655 | a MEK1/2 inhibitor | Homo sapiens | |
CH4987655 | or RO4987655, a non-ATP competitive inhibitor, highly selective for MEK1 | Homo sapiens | |
E6201 | blocks proliferation of many of the cell lines typically used in testing MEK inhibitors, such as Colo205 and MiaPaca-2 | Homo sapiens | |
GSK1120212 | - |
Homo sapiens | |
LL-Z1640-2 | a MEK1 inhibitor, which shows reasonable MEK inhibition but a very short half-life | Homo sapiens | |
additional information | the MEK enzyme contains a hydrophobic allosteric pocket adjacent to the ATP-binding site which allows for the design of highly selective allosteric inhibitors | Homo sapiens | |
PD0325901 | - |
Homo sapiens | |
PD184352/CI-1040 | a allosteric, non-ATP competitive MEK inhibitor | Homo sapiens | |
pemetrexed | - |
Homo sapiens | |
RDEA119 | - |
Homo sapiens | |
RDEA436 | - |
Homo sapiens | |
RO4987655 | - |
Homo sapiens | |
selumetinib | i.e. AZD6244, potent and highly selective, non-ATP competitive inhibitor of MEK1/2, MEK1 phosphorylation of ERK2. The compound inhibits growth of cell lines | Homo sapiens | |
temozolomide | - |
Homo sapiens | |
U0126 | a allosteric, non-ATP competitive MEK inhibitor | Homo sapiens | |
XL-518/GDC-0973 | selective for MEK1 relative to MEK2 | Homo sapiens |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Mg2+ | required | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + ERK1/2 | Homo sapiens | - |
ADP + phosphorylated ERK1/2 | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
- |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
A-375 cell | - |
Homo sapiens | - |
BxPC-3 cell | - |
Homo sapiens | - |
Colo-205 cell | - |
Homo sapiens | - |
colon | - |
Homo sapiens | - |
HCT-116 cell | - |
Homo sapiens | - |
HT-29 cell | - |
Homo sapiens | - |
melanoma cell | - |
Homo sapiens | - |
MiaPaCa-2 cell | - |
Homo sapiens | - |
pancreas | - |
Homo sapiens | - |
SK-MEL-28 cell | - |
Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + ERK1/2 | - |
Homo sapiens | ADP + phosphorylated ERK1/2 | - |
? |
Synonyms | Comment | Organism |
---|---|---|
MAPK kinase 1 | - |
Homo sapiens |
MAPK kinase 2 | - |
Homo sapiens |
MEK | - |
Homo sapiens |
MEK1/2 | - |
Homo sapiens |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
ATP | - |
Homo sapiens |
IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|
0.0000052 | - |
inhibition of MEK1, pH and temperature not specified in the publication | Homo sapiens | CH4987655 | |
0.000014 | - |
inhibition of MEK1 phosphorylation of ERK2, pH and temperature not specified in the publication | Homo sapiens | selumetinib | |
0.000019 | - |
inhibition of MEK1, pH and temperature not specified in the publication | Homo sapiens | BAY 869766 | |
0.000046 | - |
inhibition of MEK1, pH and temperature not specified in the publication | Homo sapiens | LL-Z1640-2 | |
0.000047 | - |
inhibition of MEK2, pH and temperature not specified in the publication | Homo sapiens | BAY 869766 | |
0.000052 | - |
inhibition of MEK1, pH and temperature not specified in the publication | Homo sapiens | AS-703026 |
General Information | Comment | Organism |
---|---|---|
metabolism | MAPK forms the backbone of four primary signal transduction cascades leading to the phosphorylation and activation of extracellular signal-regulated kinases 1 and 2 (ERK1-2), JNK, p38 and ERK5. The RAS-RAF-MEK-ERK pathway acts as a conduit to transduce signals from receptor tyrosine kinases (RTKs) to the nucleus. This pathway is intimately tied to intracellular machinery involved in cell proliferation, survival and cell migration, overview | Homo sapiens |
additional information | anaphylatoxins (mainly C5a) are key players in the initiation of arthritis and utilize the MEK kinase cascade to initiate the disease process | Homo sapiens |
physiological function | MEK signaling directly impacts both the expression of these cytokines and their downstream activation pathways | Homo sapiens |