Small molecule inhibitors targeting activator protein 1 (AP-1).
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.
Chemical Biology Program, Department of Pharmacology and Toxicology, University of Texas Medical Branch , Galveston, Texas 77555, United States.
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D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000378:metabolism; D001577:Benzophenones / Q000494:pharmacology; D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D007555:Isoxazoles / Q000494:pharmacology; D008301:Maleimides / Q000737:chemistry / Q000494:pharmacology; D058990:Molecular Targeted Therapy / Q000379:methods; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D009930:Organic Chemicals / Q000737:chemistry / Q000494:pharmacology; D011799:Quinazolines / Q000737:chemistry / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000737:chemistry* / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism; D000813:Anilides; D001549:Benzamides; D011743:Pyrimidines
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001577:Benzophenones; D001688:Biological Products; D007555:Isoxazoles; D008301:Maleimides; D009930:Organic Chemicals; D011799:Quinazolines; D054852:Small Molecule Libraries; D018808:Transcription Factor AP-1; D014157:Transcription Factors; C568912:3-(5-(4-(cyclopentyloxy)-2-hydroxybenzoyl)-2-((3-hydroxy-1,2-benzisoxazol-6-yl)methoxy)phenyl)propionic acid; C102914:N-(3,5-bis(trifluoromethyl)phenyl)-2-chloro-4-(trifluoromethyl)pyrimidine-5-carboxamide; D000813:Anilides; D001549:Benzamides; D011743:Pyrimidines; C000597429:SPC-839