JAK inhibition as a new treatment strategy for patients with COVID-19

Huang, Jin; Zhou, Chi; Zhou, Jianfeng

doi:10.1016/j.bcp.2022.115162

Cited by 18 publications

(15 citation statements)

References 176 publications

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“…Among them, JAK3 is only expressed in cells of the hematopoietic and lymphoid systems, while the remaining three are expressed in almost all cells [ 11 , 22 , 23 ]. JAK contains seven homology domains (JH1–7) and forms four structural domains: JH1, JH2, SH2, and FERM [ 23 , 24 ].…”

Section: Stat3 and Its Pathwaysmentioning

confidence: 99%

STAT3 Inhibitors: A Novel Insight for Anticancer Therapy of Pancreatic Cancer

Jiang

Dong

et al. 2022

Biomolecules

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The signal transducer and activator of transcription (STAT) is a family of intracellular cytoplasmic transcription factors involved in many biological functions in mammalian signal transduction. Among them, STAT3 is involved in cell proliferation, differentiation, apoptosis, and inflammatory responses. Despite the advances in the treatment of pancreatic cancer in the past decade, the prognosis for patients with pancreatic cancer remains poor. STAT3 has been shown to play a pro-cancer role in a variety of cancers, and inhibitors of STAT3 are used in pre-clinical and clinical studies. We reviewed the relationship between STAT3 and pancreatic cancer and the latest results on the use of STAT3 inhibitors in pancreatic cancer, with the aim of providing insights and ideas around STAT3 inhibitors for a new generation of chemotherapeutic modalities for pancreatic cancer.

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Section: Stat3 and Its Pathwaysmentioning

confidence: 99%

STAT3 Inhibitors: A Novel Insight for Anticancer Therapy of Pancreatic Cancer

Jiang

Dong

et al. 2022

Biomolecules

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“…Starting with ruxolitinib approved in 2011 (15,16), numerous JAK inhibitors have been approved and launched in the global pharmaceutical market (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32). They target one or more than one kinases among JAK1, JAK2, JAK3, and TYK2, accordingly aiming at different indications such as myelofibrosis, rheumatoid arthritis, atopic dermatitis, and psoriasis (13,14,33). Several review papers provide valuable information on JAKs and their inhibitors in the treatment of specific indications.…”

Section: Introductionmentioning

confidence: 99%

“…To perform their biological functions, JAKs form homodimers or heterodimers by binding to the same isoform or other forms. The binary combination of JAKs differs depending on specific receptors that bind their own ligands ( 7 , 14 ). Each dimeric JAK is involved in specific biological functions, most of which correspond to immune response ( 7 , 14 ).…”

Section: Introductionmentioning

confidence: 99%

“…The binary combination of JAKs differs depending on specific receptors that bind their own ligands ( 7 , 14 ). Each dimeric JAK is involved in specific biological functions, most of which correspond to immune response ( 7 , 14 ). Accordingly, dysfunctional JAKs can cause severe immune disorders by precluding normal downstream signaling in the JAK-STAT pathway.…”

Section: Introductionmentioning

confidence: 99%

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Molecular dissection of Janus kinases as drug targets for inflammatory diseases

Kwon

2022

Front. Immunol.

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The Janus kinase (JAK) family enzymes are non-receptor tyrosine kinases that phosphorylate cytokine receptors and signal transducer and activator of transcription (STAT) proteins in the JAK-STAT signaling pathway. Considering that JAK-STAT signal transduction is initiated by the binding of ligands, such as cytokines to their receptors, dysfunctional JAKs in the JAK-STAT pathway can lead to severe immune system-related diseases, including autoimmune disorders. Therefore, JAKs are attractive drug targets to develop therapies that block abnormal JAK-STAT signaling. To date, various JAK inhibitors have been developed to block cytokine-triggered signaling pathways. However, kinase inhibitors have intrinsic limitations to drug selectivity. Moreover, resistance to the developed JAK inhibitors constitutes a recently emerging issue owing to the occurrence of drug-resistant mutations. In this review, we discuss the role of JAKs in the JAK-STAT signaling pathway and analyze the structures of JAKs, along with their conformational changes for catalysis. In addition, the entire structure of the murine JAK1 elucidated recently provides information on an interaction mode for dimerization. Based on updated structural information on JAKs, we also discuss strategies for disrupting the dimerization of JAKs to develop novel JAK inhibitors.

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“…JAK-STAT inhibitors can block many proinflammatory and anti-inflammatory cytokines and have good pharmacodynamics. At the same time because of its short half-life, the extent and duration of cytokine arrest can be easily monitored by adjusting the dose and duration of treatment ( 6 , 7 ).…”

Section: Introductionmentioning

confidence: 99%

Janus kinases inhibitors for coronavirus disease-2019: A pairwise and Bayesian network meta-analysis

Niu

Lin

et al. 2022

Front. Med.

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BackgroundJAK (Janus kinases) inhibitors have been proposed as a promising treatment option for the coronavirus disease-2019 (COVID-19). However, the benefits of JAK inhibitors and the optimum thereof for COVID-19 have not been adequately defined.MethodsDatabases were searched from their inception dates to 17 June 2022. Eligible studies included randomized controlled trials and observational studies. Extracted data were analyzed by pairwise and network meta-analysis. The primary outcome was the coefficient of mortality.ResultsTwenty-eight studies of 8,206 patients were included and assessed qualitatively (modified Jadad and Newcastle–Ottawa Scale scores). A pairwise meta-analysis revealed that JAK inhibitors effectively reduced the mortality (OR = 0.54; 95% CI: 0.46–0.63; P < 0.00001; I2 = 32%) without increasing the risk of adverse events (OR = 1.02; 95% CI: 0.88–1.18; P = 0.79; I2 = 12%). In a network meta-analysis, clinical efficacy benefits were seen among different types of JAK inhibitors (baricitinib, ruxolitinib, and tofacitinib) without the observation of a declined incidence of adverse events. The assessment of rank probabilities indicated that ruxolitinib presented the greatest likelihood of benefits regarding mortality and adverse events.ConclusionJAK inhibitors appear to be a promising treatment for COVID-19 concerning reducing mortality, and they do not increase the risk of adverse events vs. standard of care. A network meta-analysis suggests that mortality benefits are associated with specific JAK inhibitors, and among these, ruxolitinib presents the greatest likelihood of having benefits for mortality and adverse events.Systematic review registration[www.crd.york.ac.uk/prospero], identifier [CRD42022343338].

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JAK inhibition as a new treatment strategy for patients with COVID-19

Cited by 18 publications

References 176 publications

STAT3 Inhibitors: A Novel Insight for Anticancer Therapy of Pancreatic Cancer

STAT3 Inhibitors: A Novel Insight for Anticancer Therapy of Pancreatic Cancer

Molecular dissection of Janus kinases as drug targets for inflammatory diseases

Janus kinases inhibitors for coronavirus disease-2019: A pairwise and Bayesian network meta-analysis

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