Abstract
The protein kinase B-Raf is a critical component of the Ras/MAPK signaling pathway. An oncogenic B-Raf mutation that constitutively activates the kinase was identified in ~50% of melanoma patients and in other cancers. A structure-guided drug discovery approach enabled the development of Zelboraf, a targeted inhibitor of oncogenic B-Raf. This drug has been used successfully in the clinic to treat metastatic melanoma patients harboring B-Raf mutations.
MeSH terms
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Antineoplastic Agents / adverse effects
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Antineoplastic Agents / pharmacology*
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Drug Screening Assays, Antitumor
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Humans
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Indoles / adverse effects
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Indoles / pharmacology*
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Melanoma / drug therapy*
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Melanoma / genetics*
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Mutation*
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Protein Kinase Inhibitors / adverse effects
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Protein Kinase Inhibitors / pharmacology*
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Proto-Oncogene Proteins B-raf / antagonists & inhibitors*
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Proto-Oncogene Proteins B-raf / genetics
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Proto-Oncogene Proteins B-raf / metabolism
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Structure-Activity Relationship
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Sulfonamides / adverse effects
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Sulfonamides / pharmacology*
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Vemurafenib
Substances
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Antineoplastic Agents
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Indoles
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Protein Kinase Inhibitors
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Sulfonamides
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Vemurafenib
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Proto-Oncogene Proteins B-raf