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Clinical data | |
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Trade names | Mektovi |
Other names | MEK162, ARRY-162, ARRY-438162 |
AHFS/ Drugs.com | Monograph |
MedlinePlus | a618041 |
License data |
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Drug class | Antineoplastic agent |
ATC code | |
Legal status | |
Legal status | |
Identifiers | |
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CAS Number | |
PubChem CID | |
DrugBank | |
ChemSpider | |
UNII | |
KEGG | |
ChEBI | |
ChEMBL | |
CompTox Dashboard ( EPA) | |
ECHA InfoCard | 100.167.617 |
Chemical and physical data | |
Formula | C17H15BrF2N4O3 |
Molar mass | 441.233 g·mol−1 |
3D model ( JSmol) | |
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Binimetinib, sold under the brand name Mektovi, is an anti-cancer medication used to treat various cancers. [4] Binimetinib is a selective inhibitor of MEK, a central kinase in the tumor-promoting MAPK pathway. [5] Inappropriate activation of the pathway has been shown to occur in many cancers. [5] In June 2018 it was approved by the FDA in combination with encorafenib for the treatment of patients with unresectable or metastatic BRAF V600E or V600K mutation-positive melanoma. [6] [7] In October 2023, it was approved by the FDA for treatment of NSCLC with a BRAF V600E mutation in combination with encorafenib. [8] It was developed by Array Biopharma.
Binimetinib is an orally available inhibitor of mitogen-activated protein kinase kinase (MEK), or more specifically, a MAP2K inhibitor. [9] MEK is part of the RAS pathway, which is involved in cell proliferation and survival. MEK is upregulated in many forms of cancer. [10] 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. [11] 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. [12] 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. [13] 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. [13]
In 2015, it was in phase III clinical trials for ovarian cancer, [14] BRAF mutant melanoma, [15] and NRAS Q61 mutant melanoma. [16]
In December 2015, the company announced that the mutant-NRAS melanoma trial was successful. [17] 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. [18] NDA submitted Jun 2016, [19] and the FDA should decide by 30 June 2017. [20]
In April 2016, it was reported that the phase III trial for low-grade ovarian cancer was terminated due to lack of efficacy. [21]
Binimetinib was studied for treatment of rheumatoid arthritis, but a phase II trial did not show benefit.[ medical citation needed]
In 2017, the FDA informed Array Biopharma that the phase III trial data was not sufficient and the New Drug Application was withdrawn. [22]
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. [6] 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. [7] The trial was conducted at 162 sites in Europe, North America, and various countries around the world. [7]
In October 2023, the US Food and Drug Administration approved encorafenib with binimetinib for adults with metastatic non-small cell lung cancer (NSCLC) with a BRAF V600E mutation, as detected by an FDA-approved test. [8]
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![]() | |
Clinical data | |
---|---|
Trade names | Mektovi |
Other names | MEK162, ARRY-162, ARRY-438162 |
AHFS/ Drugs.com | Monograph |
MedlinePlus | a618041 |
License data |
|
Drug class | Antineoplastic agent |
ATC code | |
Legal status | |
Legal status | |
Identifiers | |
| |
CAS Number | |
PubChem CID | |
DrugBank | |
ChemSpider | |
UNII | |
KEGG | |
ChEBI | |
ChEMBL | |
CompTox Dashboard ( EPA) | |
ECHA InfoCard | 100.167.617 |
Chemical and physical data | |
Formula | C17H15BrF2N4O3 |
Molar mass | 441.233 g·mol−1 |
3D model ( JSmol) | |
| |
|
Binimetinib, sold under the brand name Mektovi, is an anti-cancer medication used to treat various cancers. [4] Binimetinib is a selective inhibitor of MEK, a central kinase in the tumor-promoting MAPK pathway. [5] Inappropriate activation of the pathway has been shown to occur in many cancers. [5] In June 2018 it was approved by the FDA in combination with encorafenib for the treatment of patients with unresectable or metastatic BRAF V600E or V600K mutation-positive melanoma. [6] [7] In October 2023, it was approved by the FDA for treatment of NSCLC with a BRAF V600E mutation in combination with encorafenib. [8] It was developed by Array Biopharma.
Binimetinib is an orally available inhibitor of mitogen-activated protein kinase kinase (MEK), or more specifically, a MAP2K inhibitor. [9] MEK is part of the RAS pathway, which is involved in cell proliferation and survival. MEK is upregulated in many forms of cancer. [10] 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. [11] 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. [12] 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. [13] 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. [13]
In 2015, it was in phase III clinical trials for ovarian cancer, [14] BRAF mutant melanoma, [15] and NRAS Q61 mutant melanoma. [16]
In December 2015, the company announced that the mutant-NRAS melanoma trial was successful. [17] 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. [18] NDA submitted Jun 2016, [19] and the FDA should decide by 30 June 2017. [20]
In April 2016, it was reported that the phase III trial for low-grade ovarian cancer was terminated due to lack of efficacy. [21]
Binimetinib was studied for treatment of rheumatoid arthritis, but a phase II trial did not show benefit.[ medical citation needed]
In 2017, the FDA informed Array Biopharma that the phase III trial data was not sufficient and the New Drug Application was withdrawn. [22]
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. [6] 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. [7] The trial was conducted at 162 sites in Europe, North America, and various countries around the world. [7]
In October 2023, the US Food and Drug Administration approved encorafenib with binimetinib for adults with metastatic non-small cell lung cancer (NSCLC) with a BRAF V600E mutation, as detected by an FDA-approved test. [8]
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