Chemistry:GSK2981278
From HandWiki
GSK2981278 is a drug which acts as a potent and selective inverse agonist of the receptor RAR-related orphan receptor gamma (RORγ). It has anti-inflammatory effects mediated by blocking production of various inflammatory mediators such as IL-1β, IL-6, IL-17 and TNFα, and was researched for the treatment of inflammatory conditions such as psoriasis, though it showed disappointing results in human clinical trials due to poor pharmacokinetic properties. However, it continues to be widely used for basic research into the function of RORγ and as a lead compound for the development of related drugs.[1][2][3][4][5][6][7]
References
- ↑ "A phase I randomized controlled trial to evaluate safety and clinical effect of topically applied GSK2981278 ointment in a psoriasis plaque test". The British Journal of Dermatology 178 (6): 1427–1429. June 2018. doi:10.1111/bjd.16131. PMID 29150844.
- ↑ "Discovery of 2H-chromone-4-one based sulfonamide derivatives as potent retinoic acid receptor-related orphan receptor γt inverse agonists". European Journal of Medicinal Chemistry 229. 5 February 2022. doi:10.1016/j.ejmech.2021.114065. PMID 34971876.
- ↑ "Inhibition of Nuclear Receptor Related Orphan Receptor γ Ameliorates Mechanical Hypersensitivity Through the Suppression of Spinal Microglial Activation". Neuroscience 526: 223–236. 21 August 2023. doi:10.1016/j.neuroscience.2023.07.002. PMID 37419402.
- ↑ "Discovery of novel and potent sulfonamide derivatives as orally available drug for psoriasis". Bioorganic Chemistry 153. December 2024. doi:10.1016/j.bioorg.2024.107853. PMID 39396455.
- ↑ "Discovery of 1-(Phenylsulfonyl)-1,2,3,4-tetrahydroquinoline Derivative as Orally Bioavailable and Safe RORγt Inverse Agonists for Potential Treatment of Rheumatoid Arthritis". Journal of Medicinal Chemistry 67 (22): 20315–20342. 28 November 2024. doi:10.1021/acs.jmedchem.4c01727. PMID 39546350.
- ↑ "Discovery of Novel N-Sulfonamide-tetrahydroquinolines as Potent Retinoic Acid Receptor-Related Orphan Receptor γt (RORγt) Inverse Agonists for the Treatment of Psoriasis". Journal of Medicinal Chemistry 67 (23): 21400–21420. 12 December 2024. doi:10.1021/acs.jmedchem.4c02318. PMID 39611350.
- ↑ "Double negative T cells promote surgery-induced neuroinflammation, microglial engulfment and cognitive dysfunction via the IL-17/CEBPβ/C3 pathway in adult mice". Brain, Behavior, and Immunity 123: 965–981. January 2025. doi:10.1016/j.bbi.2024.10.029. PMID 39491565. https://hub.hku.hk/handle/10722/358821.
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