Rahul Sharma (Editor)

MEK inhibitor

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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 significance.)

Contents

Hence MEK inhibitors have potential for treatment of some cancers, especially BRAF-mutated melanoma, and KRAS/BRAF mutated colorectal cancer.

Approved for clinical use

  • Trametinib (GSK1120212), FDA-approved to treat BRAF-mutated melanoma. Also studied in combination with BRAF inhibitor dabrafenib to treat BRAF-mutated melanoma.
  • Cobimetinib or XL518, 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.

    • In clinical trials

  • Binimetinib (MEK162), is currently in phase 3 clinical trials for ovarian cancer, BRAF mutant melanoma, and NRAS mutant melanoma.
  • Selumetinib, had a phase 2 clinical trial for non-small cell lung cancer (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.
  • 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
  • TAK-733, preclinical for multiple myeloma.

    • References

    MEK inhibitor Wikipedia
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