The product is an oral and small molecule inhibitor of MEK1 and
MEK2. It was evaluated in various phase one and phase two clinical trials, that included more than 200 patients.
The company said Mirdametinib is an oral, small molecule inhibitor of MEK1 and
MEK2. MEK proteins occupy a pivotal position in the MAPK pathway, a key signaling network that regulates cell growth and survival and that plays a central role in multiple oncology and rare disease indications.
To further confirm that DAB2IP regulates cell growth and EMT via ERK1/2 pathway, we treated DAB2IP-deficient cells with U0126, a highly selective inhibitor of both MEK1 and
MEK2 (a type of MAPK/ ERK kinase).
(21) Both Mek1 and
Mek2 deficiency lead to severe impairment of gliogenesis in vivo and to a reduction in JAK-STAT3 signal activation in cultured NSCs through a decrease in the expression of gp130, which contributes to mediating the effects of the entire IL-6 family of cytokines.
U0126 (a highly selective inhibitor of MEK1 and
MEK2, which are kinase of ERK1/2) was from Cell Signaling Technology (CST).
(12) Some of these mutations, such as MEK1 P124 (substitution of proline at position 124), MEK1 C121S (serine for cysteine substitution at position 121), and
MEK2 C125S (serine for cysteine substitution at position 125), are particularly concerning because they might confer resistance to targeted drugs.
Phospho-p44/42 MAPK (ERK1/2) ([Thr.sup.202]/ [Tyr.sup.204], E10) antibody, p44/42 MAPK (ERK1/2) antibody, MEK1 antibody,
MEK2 antibody, and horseradish peroxidase-conjugated secondary anti-rabbit and anti-mouse antibodies were purchased from Cell Signaling Technology (Beverly, MA, USA).
Similar binding affinities of AKT, MEK1,
MEK2, STAT3 and mTOR were calculated for honokiol (range from -9.0 [+ or -]0.01 to 7.40 [+ or -]0.01 kcal/mol) compared to corresponding control inhibitor compounds for these signal transducers.
The new drug, called selumetinib, works by disrupting the enzymes (MEK1 and
MEK2) which are involved in the signalling pathway associated with these genes, and has been shown in preliminary research to disrupt the growth of melanoma cells in the laboratory and now in early stage human trials.
MEK inhibitor-induced receptor tyrosine kinase (RTK) stimulation overcame
MEK2 inhibition, reactivating ERK and resulting in drug resistance.
Zhang H, Feng H, Luo L, Zhou Q, Luo Z, Peng Y (2010) Distinct effects of knocking down MEK1 and
MEK2 on replication of herpes simplex virus type 2.
Implication of MEK1 and
MEK2 in the establishment of the blood-placenta barrier during placentogenesis in mouse.
