Abstract
Activator protein 1 (AP-1) is a pivotal transcription factor that regulates a wide range of cellular processes including proliferation, apoptosis, differentiation, survival, cell migration, and transformation. Accumulating evidence supports that AP-1 plays an important role in several severe disorders including cancer, fibrosis, and organ injury, as well as inflammatory disorders such as asthma, psoriasis, and rheumatoid arthritis. AP-1 has emerged as an actively pursued drug discovery target over the past decade. Excitingly, a selective AP-1 inhibitor T-5224 (51) has been investigated in phase II human clinical trials. Nevertheless, no effective AP-1 inhibitors have yet been approved for clinical use. Despite significant advances achieved in understanding AP-1 biology and function, as well as the identification of small molecules modulating AP-1 associated signaling pathways, medicinal chemistry efforts remain an urgent need to yield selective and efficacious AP-1 inhibitors as a viable therapeutic strategy for human diseases.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anti-Inflammatory Agents, Non-Steroidal / chemistry
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology
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Arthritis, Rheumatoid / drug therapy
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Arthritis, Rheumatoid / metabolism
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Benzophenones / pharmacology
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Biological Products / chemistry
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Biological Products / pharmacology
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Humans
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Inflammation / drug therapy
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Inflammation / metabolism
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Isoxazoles / pharmacology
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Maleimides / chemistry
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Maleimides / pharmacology
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Molecular Targeted Therapy / methods
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Neoplasms / drug therapy
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Neoplasms / metabolism
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Organic Chemicals / chemistry
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Organic Chemicals / pharmacology
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Quinazolines / chemistry
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Quinazolines / pharmacology
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Signal Transduction / drug effects
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Small Molecule Libraries / chemistry
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Small Molecule Libraries / pharmacology*
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Transcription Factor AP-1 / chemistry*
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Transcription Factor AP-1 / metabolism*
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Transcription Factors / chemistry
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Transcription Factors / metabolism
Substances
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3-(5-(4-(cyclopentyloxy)-2-hydroxybenzoyl)-2-((3-hydroxy-1,2-benzisoxazol-6-yl)methoxy)phenyl)propionic acid
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Anti-Inflammatory Agents, Non-Steroidal
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Benzophenones
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Biological Products
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Isoxazoles
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Maleimides
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N-(3,5-bis(trifluoromethyl)phenyl)-2-chloro-4-(trifluoromethyl)pyrimidine-5-carboxamide
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Organic Chemicals
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Quinazolines
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SPC-839
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Small Molecule Libraries
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Transcription Factor AP-1
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Transcription Factors