Targeting the JAK-STAT pathway in autoimmune diseases and cancers: A focus on molecular mechanisms and therapeutic potential

Tzeng, Hong-Tai; Chyuan, I‐Tsu; Lai, Jenn‐Haung

doi:10.1016/j.bcp.2021.114760

Cited by 57 publications

(34 citation statements)

References 113 publications

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“…This drug, a JAK1/JAK2 inhibitor, is also in clinical trials as an oral treatment for psoriasis and rheumatoid arthritis. 19 Tofacitinib, a JAK1/JAK2/JAK3 inhibitor, is approved for the treatment of polyarticular course juvenile idiopathic arthritis, psoriatic arthritis, rheumatoid arthritis, and ulcerative colitis. Tofacitinib is currently in clinical trials for systemic lupus erythematosus, primary Sjogren’s syndrome, Takayasu arteritis, diffuse cutaneous systemic sclerosis, and dermatomyositis.…”

Section: Introductionmentioning

confidence: 99%

“…Tofacitinib is currently in clinical trials for systemic lupus erythematosus, primary Sjogren’s syndrome, Takayasu arteritis, diffuse cutaneous systemic sclerosis, and dermatomyositis. 19 Baricitinib, a JAK1/JAK2 inhibitor, is approved for rheumatoid arthritis and is currently in clinical trials for systemic lupus erythematosus, juvenile idiopathic arthritis, primary Sjogren´s syndrome, and psoriasis. 19 The European Union has approved upadacitinib, a JAK1 selective inhibitor for rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, it is also in clinical trials for Takayasu arteritis, giant cell arteritis, Crohn’s disease, systemic lupus erythematosus, and ulcerative colitis.…”

Section: Introductionmentioning

confidence: 99%

“… 19 Baricitinib, a JAK1/JAK2 inhibitor, is approved for rheumatoid arthritis and is currently in clinical trials for systemic lupus erythematosus, juvenile idiopathic arthritis, primary Sjogren´s syndrome, and psoriasis. 19 The European Union has approved upadacitinib, a JAK1 selective inhibitor for rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, it is also in clinical trials for Takayasu arteritis, giant cell arteritis, Crohn’s disease, systemic lupus erythematosus, and ulcerative colitis. 19 Filgotinib, a JAK1 selective inhibitor, is approved in the European Union and Japan for rheumatoid arthritis, is also being studied for Crohn’s disease, ankylosing spondylitis, psoriatic arthritis, and Sjogren’s syndrome.…”

Section: Introductionmentioning

confidence: 99%

“… 19 The European Union has approved upadacitinib, a JAK1 selective inhibitor for rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, it is also in clinical trials for Takayasu arteritis, giant cell arteritis, Crohn’s disease, systemic lupus erythematosus, and ulcerative colitis. 19 Filgotinib, a JAK1 selective inhibitor, is approved in the European Union and Japan for rheumatoid arthritis, is also being studied for Crohn’s disease, ankylosing spondylitis, psoriatic arthritis, and Sjogren’s syndrome. It is also being studied for Crohn’s disease, ankylosing spondylitis, psoriatic arthritis, and Sjogren’s syndrome.…”

Section: Introductionmentioning

confidence: 99%

“…It is also being studied for Crohn’s disease, ankylosing spondylitis, psoriatic arthritis, and Sjogren’s syndrome. 19 Peficitinib a Pan-JAK inhibitor is approved in Japan and South Korea for rheumatoid arthritis, and is also in clinical trials for psoriasis, and ulcerative colitis. 19 …”

Section: Introductionmentioning

confidence: 99%

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Evaluating the Therapeutic Potential of Ritlecitinib for the Treatment of Alopecia Areata

Ramírez-Marín

Tosti²

2022

DDDT

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Alopecia areata (AA) is an autoimmune condition that causes patchy hair loss, affecting up to 147 million people globally. Currently, there are no treatments approved by US Food and Drug Administration (FDA) specific for AA, and there are few effective therapeutic options for widespread and persistent illness. There is an ongoing need for a treatment that demonstrates a good clinical response with a benefit-risk ratio that is suitable for long-term use, especially for patients with chronic, extensive disease. Several clinical trials and case studies that have assessed Janus kinase inhibitors have had encouraging results. Ritlecitinib, a selective JAK3/TEC kinase inhibitor has been demonstrated to inhibit the action of signaling molecules and immune cells that are responsible for hair loss in people with alopecia areata. Furthermore, several clinical trials are investigating the utility of ritlecitinib in patients with vitiligo, rheumatoid arthritis, Crohn’s disease, and ulcerative colitis. Advantages of using ritlecitinib when compared with other non-selective JAK inhibitors include avoiding JAK1/JAK2 inhibition’s clinical repercussions, which include pharmacodynamic effects such as increased cholesterol and liver enzymes, and those related to JAK2 inhibition (thrombocytopenia, anemia). Treatment with Ritlecitinib 50 mg and 30 mg daily for 24 weeks has been shown to induce hair regrowth with a significant proportion of patients reaching SALT 20 (≤20% scalp hair loss) after six months of therapy compared to placebo. Additional research is needed for long-term effects.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Evaluating the Therapeutic Potential of Ritlecitinib for the Treatment of Alopecia Areata

Ramírez-Marín

Tosti²

2022

DDDT

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A better understanding of the role of the CTLA–CD80/86 axis in the treatment of autoimmune diseases

Darvish,

Kheder,

Faraj

et al. 2023

Cell Biochemistry & Function

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Autoimmune diseases are diseases in which the regulatory mechanisms of the immune response are disturbed. As a result, the body loses self‐tolerance. Since one of the main regulatory mechanisms of the immune response is the CTLA4–CD80/86 axis, this hypothesis suggests that autoimmune diseases potentially share a similar molecular basis of pathogenesis. Hence, investigating the CTLA4–CD80/86 axis may be helpful in finding an appropriate treatment strategy. Therefore, this study aims to investigate the molecular basis of the CTLA4–CD80/86 axis in the regulation of the immune response, and then its role in developing some autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes, and multiple sclerosis. As well, the main therapeutic strategies affecting the CTLA4–CD80/86 axis have been summarized to highlight the importance of this axis in management of autoimmune diseases.

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Covalent inhibitors: An ambitious approach for the discovery of newer oncotherapeutics

Cheke,

Kharkar

2023

Drug Development Research

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Covalent inhibitors have been used to treat several diseases for over a century. However, strategic approaches for the rational design of covalent drugs have taken a definitive shape in recent times. Since the first appearance of covalent inhibitors in the late 18th century, the field has grown tremendously and around 30% of marketed drugs are covalent inhibitors especially, for oncology indications. However, the off‐target toxicity and safety concerns can be significant issues related to the covalent drugs. Covalent kinase inhibitor (CKI) targeted oncotherapeutics has advanced dramatically over the last two decades since the discovery of afatinib (Gilotrif®), an EGFR inhibitor. Since then, US FDA has approved 10 CKIs for diverse cancer targets. The present review broadly summarizes the ongoing development in the discovery of newer CKIs from 2016 till the end of 2022. We believe that these efforts will assist the modern medicinal chemist actively working in the field of CKI discovery for varied indications.

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Targeting the JAK-STAT pathway in autoimmune diseases and cancers: A focus on molecular mechanisms and therapeutic potential

Cited by 57 publications

References 113 publications

Evaluating the Therapeutic Potential of Ritlecitinib for the Treatment of Alopecia Areata

Evaluating the Therapeutic Potential of Ritlecitinib for the Treatment of Alopecia Areata

A better understanding of the role of the CTLA–CD80/86 axis in the treatment of autoimmune diseases

Covalent inhibitors: An ambitious approach for the discovery of newer oncotherapeutics

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