Abstract：
:Aberrant activation of the three-layered protein kinase cascade, Raf/MEK/ERK, is often detected in human cancer, which is mainly attributed to the oncogenic alterations of RAF, or its upstream activators RAS or cell surface receptor tyrosine kinases. Deregulated activity of the Raf/MEK/ERK pathway drives uncontrolled tumor cell proliferation and survival, thus providing a rational therapeutic target for the treatment of many cancers. While Raf, MEK1/2, and ERK1/2 are equally important targets for the design of therapeutic small molecular weight inhibitors, the effort to develop MEK1/2-specific inhibitors has been greatly successful. Particularly, MEK1/2 have been relatively advantageous for the design of highly selective adenosine triphosphate (ATP)-noncompetitive inhibitors. Indeed, a plethora of highly selective and potent MEK1/2 inhibitors are now available and many of those inhibitors have been evaluated for their therapeutic potential. Herein, we review different MEK1/2 inhibitors that have been studied for their inhibitory mechanisms and therapeutic potential in cancer. Some of the key structural features of MEK1/2 that are important for the efficacy of these inhibitors are also discussed. In addition, we discuss current challenges and future prospective in using these advanced MEK1/2 inhibitors for cancer therapy.
journal_name
Semin Oncoljournal_title
Seminars in oncologyauthors
Wu PK,Park JIdoi
10.1053/j.seminoncol.2015.09.023subject
Has Abstractpub_date
2015-12-01 00:00:00pages
849-62issue
6eissn
0093-7754issn
1532-8708pii
S0093-7754(15)00193-1journal_volume
42pub_type
杂志文章,评审abstract：:Combination therapy consisting of Lipiodol (Laboratoire Guerbet, Villepinte, France) containing styrene maleic acid neocarzinostatin and transcatheter arterial embolization (L-TAE) has been an important conservative therapy for hepatocellular carcinoma (HCC). We examined the clinical and pathologic characteristics of ...
journal_title：Seminars in oncology
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journal_title：Seminars in oncology
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journal_title：Seminars in oncology
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journal_title：Seminars in oncology
pub_type： 杂志文章,评审
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journal_title：Seminars in oncology
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journal_title：Seminars in oncology
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journal_title：Seminars in oncology
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journal_title：Seminars in oncology
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doi：10.1016/s0093-7754(01)90251-9
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