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Competition in the TYK2 drug market is intensifying, and Pfizer will sell 2 drugs under development

https://worldwidechemicallabs.us/

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Competition in the TYK2 drug market is intensifying, and Pfizer will sell 2 drugs under development

https://worldwidechemicallabs.us/

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Pirnie R, P Gillespie K, Mesaros C, Blair IA. Reappraisal of oxidized HMGB1 as a mediator and biomarker. Future Sci OA. 2023 Feb 10;8(10):FSO828. doi: 10.2144/fsoa-2022-0052. PMID: 36874369; PMCID: PMC9979160.

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Koutsodendris N, Blumenfeld J, Agrawal A, Traglia M, Yip O, Rao A, Kim MJ, Nelson MR, Wang YH, Grone B, Hao Y, Thomas R, Zilberter M, Yoon SY, Arriola P, Huang Y. APOE4-promoted gliosis and degeneration in tauopathy are ameliorated by pharmacological inhibition of HMGB1 release. Cell Rep. 2023 Oct 31;42(10):113252. doi: 10.1016/j.celrep.2023.113252. Epub 2023 Oct 19. PMID: 37863057.

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What about HMGB1 as a potential target. Intriguing recent Alzheimer's paper.

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Dec 8, 2023·edited Dec 8, 2023Author

I haven't seen the recent work can you link it? I have generally seen strong preclinical data for the role of alarmins like HMGB1, IL-33 and other DAMPs in AD, PD and in CNS. In my mind, I wonder whether targeting upstream mechanisms of cell death that allow for alarmin release (e.g. pyroptosis, necroptosis) may be more effective than mAbs against individual alarmins like HMGB1, or antagonists of the RAGE or TLR4 receptors. Denali's ALS Ph2 HIMALAYA trial with its RIPK1 inhibitor (blocking necroptosis) is ongoing, results potentially in 2024.

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