|Other names||MEK162, ARRY-162, ARRY-438162|
|Side effects||Tiredness, nausea, diarrhea, abdominal pain|
|Typical dose||45 mg BID|
|Chemical and physical data|
|Molar mass||441.233 g·mol−1|
|3D model (JSmol)|
Binimetinib, sold under the brand name Mektovi, is as medication used to treat melanoma. Specifically it is used with encorafenib for cases that are BRAF V600 positive and cannot be removed by surgery. It is taken by mouth.
Common side effects include tiredness, nausea, diarrhea, and abdominal pain. Other side effects may include heart damage, blood clots, eye problems, interstitial lung disease, liver problems, muscle breakdown, and bleeding. Use in pregnancy may harm the baby. It works by blocking MEK, preventing its activation by BRAF, thereby slowing cancer growth.
Binimetinib was approved for medication use in the United States and Europe in 2018. In the United Kingdom 4 weeks of treatment costs the NHS about £4,500 as of 2021. This amount in the United States costs about 12,800 USD.
It is typically taken as 45 mg twice per day.
Mechanism of action
Binimetinib is an orally available inhibitor of mitogen-activated protein kinase kinase (MEK), or more specifically, a MAP2K inhibitor. MEK is part of the RAS pathway, which is involved in cell proliferation and survival. MEK is upregulated in many forms of cancer. Binimetinib, uncompetitive with ATP, binds to and inhibits the activity of MEK1/2 kinase, which has been shown to regulate several key cellular activities including proliferation, survival, and angiogenesis. MEK1/2 are dual-specificity threonine/tyrosine kinases that play key roles in the activation of the RAS/RAF/MEK/ERK pathway and are often upregulated in a variety of tumor cell types. Inhibition of MEK1/2 prevents the activation of MEK1/2 dependent effector proteins and transcription factors, which may result in the inhibition of growth factor-mediated cell signaling. As demonstrated in preclinical studies, this may eventually lead to an inhibition of tumor cell proliferation and an inhibition in production of various inflammatory cytokines including interleukin-1, -6 and tumor necrosis factor.
In December 2015, the company announced that the mutant-NRAS melanoma trial was successful. In the trial, those receiving binimetinib had a median progression-free survival of 2.8 months versus 1.5 months for those on the standard dacarbazine treatment. NDA submitted Jun 2016, and the FDA should decide by 30 June 2017.
In April 2016, it was reported that the phase III trial for low-grade ovarian cancer was terminated due to lack of efficacy.
In June 2018, it was approved for the treatment of certain melanomas by the U.S. Food and Drug Administration (FDA) in combination with encorafenib. The FDA approved binimetinib based primarily on evidence from one clinical trial (NCT01909453) of 383 patients with BRAF V600 mutation-positive melanoma that was advanced or could not be removed by surgery. The trial was conducted at 162 sites in Europe, North America, and various countries around the world.
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- Clinical trial number NCT01849874 for "A Study of MEK162 vs. Physician's Choice Chemotherapy in Patients With Low-grade Serous Ovarian, Fallopian Tube or Peritoneal Cancer" at ClinicalTrials.gov
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- Clinical trial number NCT01763164 for "Study Comparing the Efficacy of MEK162 Versus Dacarbazine in Unresectable or Metastatic NRAS Mutation-positive Melanoma" at ClinicalTrials.gov
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