Small molecule inhibitors targeting activator protein 1 (AP-1)

• Published in: Journal of medicinal chemistry Vol. 57; no. 16; p. 6930
• Main Authors: Ye, Na, Ding, Ye, Wild, Christopher, Shen, Qiang, Zhou, Jia
• Format: Journal Article
• Language: English
• Published: United States 28.08.2014
• Subjects: Animals; Anti-Inflammatory Agents, Non-Steroidal - chemistry; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - metabolism; Benzophenones - pharmacology; Biological Products - chemistry; Biological Products - pharmacology; Humans; Inflammation - drug therapy; Inflammation - metabolism; Isoxazoles - pharmacology; Maleimides - chemistry; Maleimides - pharmacology; Molecular Targeted Therapy - methods; Neoplasms - drug therapy; Neoplasms - metabolism; Organic Chemicals - chemistry; Organic Chemicals - pharmacology; Quinazolines - chemistry; Quinazolines - pharmacology; Signal Transduction - drug effects; Small Molecule Libraries - chemistry; Small Molecule Libraries - pharmacology; Transcription Factor AP-1 - chemistry; Transcription Factor AP-1 - metabolism; Transcription Factors - chemistry; Transcription Factors - metabolism
• ISSN: 1520-4804; 1520-4804
• DOI: 10.1021/jm5004733

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.