A MEK inhibitor is a chemical or drug that inhibits the

mitogen-activated protein kinase kinase Mitogen-activated protein kinase kinase (also known as MAP2K, MEK, MAPKK) is a dual-specificity kinase enzyme which phosphorylates mitogen-activated protein kinase (MAPK). MAP2K is classified as . There are seven genes: * (a.k.a. MEK1) * ( ...

enzymes

MEK1 Dual specificity mitogen-activated protein kinase kinase 1 is an enzyme that in humans is encoded by the ''MAP2K1'' gene. Function The protein encoded by this gene is a member of the dual-specificity protein kinase family that acts as a mito ...

and/or

MEK2 Dual specificity mitogen-activated protein kinase kinase 2 is an enzyme that in humans is encoded by the ''MAP2K2'' gene. It is more commonly known as MEK2, but has many alternative names including CFC4, MKK2, MAPKK2 and PRKMK2. Function The ...

. They can be used to affect the

MAPK/ERK pathway The MAPK/ERK pathway (also known as the Ras-Raf-MEK-ERK pathway) is a chain of proteins in the cell that communicates a signal from a receptor on the surface of the cell to the DNA in the nucleus of the cell. The signal starts when a signaling ...

which is often overactive in some cancers. (See MAPK/ERK pathway#Clinical significance.) Hence MEK inhibitors have potential for treatment of some cancers, especially BRAF-mutated

melanoma Melanoma, also redundantly known as malignant melanoma, is a type of skin cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, intestines, or eye ( ...

, and

KRAS ''KRAS'' ( Kirsten rat sarcoma virus) is a gene that provides instructions for making a protein called K-Ras, a part of the RAS/MAPK pathway. The protein relays signals from outside the cell to the cell's nucleus. These signals instruct the cell ...

/BRAF mutated

colorectal cancer Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel ...

Approved for clinical use

Binimetinib Binimetinib, also known as Mektovi and ARRY-162, is an anti-cancer small molecule that was developed by Array Biopharma to treat various cancers. Binimetinib is a selective inhibitor of MEK, a central kinase in the tumor-promoting MAPK pathway. ...

(MEK162), approved by the FDA in June 2018 in combination with

encorafenib Encorafenib, sold under the brand name Braftovi, is a medication for the treatment of certain melanoma cancers. It is a small molecule BRAF inhibitor that targets key enzymes in the MAPK signaling pathway. This pathway occurs in many different ...

for the treatment of patients with unresectable or metastatic BRAF V600E or V600K mutation-positive melanoma. *

Cobimetinib Cobimetinib, sold under the brand name Cotellic, is an anti-cancer medication used in combination with vemurafenib (Zelboraf) alone or with both vemurafenib and atezolizumab (Tecentriq) to treat melanoma. Cobimetinib is a MEK inhibitor. Cotell ...

XL518 Cobimetinib, sold under the brand name Cotellic, is an anti-cancer medication used in combination with vemurafenib (Zelboraf) alone or with both vemurafenib and atezolizumab (Tecentriq) to treat melanoma. Cobimetinib is a MEK inhibitor. Cotellic ...

, approved by US FDA in Nov 2015 for use in combination with vemurafenib (Zelboraf(R)), for treatment of advanced melanoma with a BRAF V600E or V600K mutation. *

Selumetinib Selumetinib ( ), sold under the brand name Koselugo, is a medication for the treatment of children, two years of age and older, with neurofibromatosis type I (NF-1), a genetic disorder of the nervous system causing tumors to grow on nerves. I ...

, had a phase 2

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, diet ...

for

non-small cell lung cancer Non-small-cell lung cancer (NSCLC) is any type of epithelial lung cancer other than small-cell lung carcinoma (SCLC). NSCLC accounts for about 85% of all lung cancers. As a class, NSCLCs are relatively insensitive to chemotherapy, compared to s ...

(NSCLC) which demonstrated an improvement in PFS, and is now in phase III development in KRAS mutation positive NSCLC (SELECT-1, NCT01933932). Other ph 3 clinical trials underway include uveal melanoma (failed), and differentiated thyroid carcinoma. * Trametinib (GSK1120212), FDA-approved to treat BRAF-mutated melanoma. Also studied in combination with BRAF inhibitor dabrafenib to treat BRAF-mutated melanoma.

In clinical trials

* PD-325901, for breast cancer, colon cancer, and melanoma A phase II trial for advanced non-small cell lung cancer "did not meet its primary efficacy end point".

Others

* CI-1040,

PD035901 PD, P.D., or Pd may refer to: Arts and media * ''People's Democracy'' (newspaper), weekly organ of the Communist Party of India (Marxist) * ''The Plain Dealer'', a Cleveland, Ohio, US newspaper * Post Diaspora, a time frame in the ''Honorverse'' ...

TAK-733 A MEK inhibitor is a chemical or drug that inhibits the mitogen-activated protein kinase kinase enzymes MEK1 and/or MEK2. They can be used to affect the MAPK/ERK pathway which is often overactive in some cancers. (See MAPK/ERK pathway#Clinical si ...

, preclinical for

multiple myeloma Multiple myeloma (MM), also known as plasma cell myeloma and simply myeloma, is a cancer of plasma cells, a type of white blood cell that normally produces antibodies. Often, no symptoms are noticed initially. As it progresses, bone pain, ...

Pre-clinical investigation

Clinically approved MEK inhibitor

has been investigated in combination with PI3K inhibition in pre-clinical models of lung cancer, where the combined treatment approach lead to a synergistic anti-cancer response. Co-targeted therapeutic approaches to have been suggested to induce improved anti-cancer effects, due to blockade of compensatory signalling, prevention or delay of acquired resistance to treatment, and the possibility of reducing dosing of each compound.

References

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