GLPG0634又称为Filgotinib,是一种口服生物活性的、选择性JAK1抑制剂(IC50=10 nM,Kd=11 nM),并抑制JAK2、JAK3和TYK2,IC50分别为28 nM、810 nM和 116 nM。GLPG0634有效抑制Th1、Th2和Th17分化。另外,在胶原诱导的类风湿模型中,GLPG0634具有明显作用,导致足肿胀、软骨以及骨降解、炎症因子水平明显降低。
目前,GLPG0634已用于类风湿关节炎(RA)的Phase 2B,以及克罗恩病(Crohn’s disease,CD)的Phase 2A研究阶段。
参考文献
[1] Rompaey LV, et al. Preclinical Characterization of GLPG0634, a Selective Inhibitor of JAK1, for the Treatment of Inflammatory Diseases. The Journal of Immunology 191(7): 3568-3577 (2013).
[2] Menet CJ, et al. Triazolopyridines as Selective JAK1 Inhibitors: From Hit Identification to GLPG0634. J. Med. Chem., 57 (22): 9323–9342 (2014).
[3] Namour F, et al. AB0460 Glpg0634, A Selective JAK1 Inhibitor, Confirms Its Low Liability for Drug-Drug Interactions. Ann Rheum Dis 73: 960 (2014).
[4] Namour F, et al. Pharmacokinetics and Pharmacokinetic/Pharmacodynamic Modeling of Filgotinib (GLPG0634), a Selective JAK1 Inhibitor, in Support of Phase IIB Dose Selection. Clinical Pharmacokinetics 54(8): 859-874 (2015).
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