Jones, J. Howard; Xin, Zhili; Himmelbauer, Martin; Dechantsreiter, Michael; Enyedy, Istvan; Hedde, Joseph; Fang, Terry; Coomaraswamy, Janaky; King, Kristopher W.; Murugan, Paramasivam; Santoro, Joseph C.; Hesson, Thomas; Walther, Dirk M.; Wei, Ru; Zheng, Fengmei; Marcotte, Douglas J.; Spilker, Kerri; Kumar, P. Rajesh; Liu, Ying; Gilfillan, Rab; Gonzalez-Lopez de Turiso, Felix published the artcile< Discovery of Potent, Selective, and Brain-Penetrant Apoptosis Signal-Regulating Kinase 1 (ASK1) Inhibitors that Modulate Brain Inflammation In Vivo>, Electric Literature of 6482-24-2, the main research area is ASK1 inhibitor brain inflammation pharmacokinetic penetration.
Apoptosis signal-regulating kinase 1 (ASK1) is one of the key mediators of the cellular stress response that regulates inflammation and apoptosis. To probe the therapeutic value of modulating this pathway in preclin. models of neurol. disease, we further optimized the profile of our previously reported inhibitor 3. This effort led to the discovery of 32, a potent (cell IC50 = 25 nM) and selective ASK1 inhibitor with suitable pharmacokinetic and brain penetration (rat Cl/Clu = 1.6/56 L/h/kg and Kp,uu = 0.46) for proof-of-pharmacol. studies. Specifically, the ability of 32 to inhibit ASK1 in the central nervous system (CNS) was evaluated in a human tau transgenic (Tg4510) mouse model exhibiting elevated brain inflammation. In this study, transgenic animals treated with 32 (at 3, 10, and 30 mg/kg, BID/PO for 4 days) showed a robust reduction of inflammatory markers (e.g., IL-1β) in the cortex, thus confirming inhibition of ASK1 in the CNS.
Journal of Medicinal Chemistry published new progress about Anti-inflammatory agents. 6482-24-2 belongs to class ethers-buliding-blocks, and the molecular formula is C3H7BrO, Electric Literature of 6482-24-2.
Referemce:
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem