Baricitinib (LY3009104, INCB028050) is a potent orally active inhibitor of JAK1 and JAK2 with IC50 values of 5.9 and 5.7nM, respectively [1]. By inhibiting JAK1 and JAK2 enzymes, Baricitinib can block the signal transduction of a variety of cytokines related to COVID-19 immunopathology, and play an antiviral effect by targeting the host factors that viral invasion cells depend on and inhibiting the up-regulation of angiotensin-converting enzyme 2 (ACE2) driven by type I interferon[2]. Baricitinib has been widely used to regulate cytokine release and related signaling of leukocyte subsets as well as inflammatory responses[3].
In vitro, Baricitinib treatment for 24 hours significantly inhibited TGF-β1-induced proliferation of Mlg cells and NIH-3T3 cells, with IC50 values of 113.3 and 148.0μM, respectively[4]. Baricitinib treatment at 5µM for 24h significantly inhibited lipopolysaccharide (10µg/ml)-induced oxidative stress and inflammation in periodontal ligament stem cells (PDLSCs) and promoted osteogenic differentiation of the cells[5].
In vivo, Baricitinib treatment via oral administration (10mg/kg) twice daily for 8 weeks inhibited abnormal B cell activation and podocyte abnormalities and effectively attenuated autoimmune features, including renal inflammation, in lupus-prone mice[6]. Oral administration of Baricitinib at a dose of 10mg/kg/day for 16 weeks suppressed metabolic disorders and ameliorated muscle steatosis, mesangial expansion, and associated proteinuria in mice induced by a high-fat and high-sugar diet[7]. Oral administration of Baricitinib at a dose of 5mg/kg/day for a week can reduce myocardial cell widening, inflammatory infiltration, and fibrous tissue hyperplasia in isoproterenol (ISO)-induced myocardial fibrosis mice[8].
References:
[1] Fridman J S, Scherle P A, Collins R, et al. Selective inhibition of JAK1 and JAK2 is efficacious in rodent models of arthritis: preclinical characterization of INCB028050[J]. The Journal of Immunology, 2010, 184(9): 5298-5307.
[2] Jorgensen S C J, Tse C L Y, Burry L, et al. Baricitinib: a review of pharmacology, safety, and emerging clinical experience in COVID‐19[J]. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 2020, 40(8): 843-856.
[3] McInnes I B, Byers N L, Higgs R E, et al. Comparison of baricitinib, upadacitinib, and tofacitinib mediated regulation of cytokine signaling in human leukocyte subpopulations[J]. Arthritis research & therapy, 2019, 21(1): 183.
[4] Gu S, Liang J, Zhang J, et al. Baricitinib attenuates bleomycin-induced pulmonary fibrosis in mice by inhibiting TGF-β1 signaling pathway[J]. Molecules, 2023, 28(5): 2195.
[5] Yang P, Shi F, Zhang Y. Baricitinib alleviates lipopolysaccharide‑induced human periodontal ligament stem cell injury and promotes osteogenic differentiation by inhibiting JAK/STAT signaling[J]. Experimental and Therapeutic Medicine, 2022, 25(2): 74.
[6] Lee J, Park Y, Jang S G, et al. Baricitinib attenuates autoimmune phenotype and podocyte injury in a murine model of systemic lupus erythematosus[J]. Frontiers in Immunology, 2021, 12: 704526.
[7] Collotta D, Hull W, Mastrocola R, et al. Baricitinib counteracts metaflammation, thus protecting against diet-induced metabolic abnormalities in mice[J]. Molecular Metabolism, 2020, 39: 101009.
[8] Feng R, Liu H, Chen Y. Baricitinib represses the myocardial fibrosis via blocking JAK/STAT and TGF-β1 pathways in vivo and in vitro[J]. BMC Cardiovascular Disorders, 2025, 25(1): 65.
Baricitinib (LY3009104, INCB028050)是一种高效口服JAK1/JAK2抑制剂，对JAK1和JAK2的IC50值分别为5.9nM和5.7nM[1]。通过抑制JAK1/JAK2酶活性，Baricitinib可阻断多种COVID-19免疫病理相关细胞因子的信号转导，并通过靶向病毒入侵细胞的宿主依赖因子及抑制I型干扰素驱动的血管紧张素转换酶2(ACE2)上调发挥抗病毒作用[2]。Baricitinib已广泛应用于细胞因子释放、白细胞亚群相关信号及炎症反应的调控[3]。
在体外，Baricitinib处理24小时能显著抑制TGF-β1诱导的Mlg细胞和NIH-3T3细胞增殖，IC50值分别为113.3 μM和148.0 μM[4]。使用5µM的Baricitinib处理牙周膜干细胞(PDLSCs)24小时，可显著抑制脂多糖(10µg/ml)诱导的氧化应激与炎症反应，并促进细胞成骨分化[4]。
在体内，每日两次口服10 mg/kg剂量的Baricitinib连续8周，能抑制狼疮易感小鼠的异常B细胞活化及足细胞异常，有效减轻肾脏炎症等自身免疫特征[6]。每日口服10 mg/kg/day剂量的Baricitinib连续16周，可抑制高脂高糖饮食诱导的小鼠代谢紊乱，改善肌肉脂肪变性、系膜扩张及相关蛋白尿[7]。每日口服5mg/kg/day剂量的Baricitinib连续1周，能减轻异丙肾上腺素(ISO)诱导的心肌纤维化小鼠的心肌细胞肥大、炎症浸润及纤维组织增生[8]。