Tofacitinib and Other Kinase Inhibitors in the Treatment of Psoriasis

Ortiz-Ibáñez, K.; Alsina, M.; Muñoz‐Santos, Carlos

doi:10.1016/j.adengl.2013.03.002

Cited by 23 publications

(50 citation statements)

References 24 publications

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“…12) Due to their ability to selectively modulate immune function, targeted JAK inhibitors are attractive candidates for some skin diseases such as psoriasis and atopic dermatitis. [13][14][15] Our computer simulation result suggested that EGCG may bind to JAK2 protein (Fig. 1C).…”

Section: Egcg Inhibited Janus Kinase (Jak)2 Activity In Vitromentioning

confidence: 99%

Epigallocatechin-3-gallate (EGCG) Suppresses the Trafficking of Lymphocytes to Epidermal Melanocytes <i>via</i> Inhibition of JAK2: Its Implication for Vitiligo Treatment

Ning

Wang

Dong

et al. 2015

Biological & Pharmaceutical Bulletin

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Vitiligo is an inflammatory skin disorder in which activated T cells play an important role in its onset and progression. Epigallocatechin-3-gallate (EGCG), the major chemical constituent of green tea, exhibits remarkable anti-oxidative and anti-inflammatory properties. EGCG administration has been confirmed to decrease the risk of vitiligo; however, the underlying mechanism is undetermined. In this study, we proved that EGCG directly inhibited the kinase activity of Janus kinase 2 (JAK2). In primary cultured human melanocytes, EGCG pre-treatment attenuated interferon ( Key words vitiligo; epigallocatechin-3-gallate; melanocyte; Janus kinase 2; chemoattractant Vitiligo is a depigmentation disorder caused by the destruction of epidermal melanocytes.1) The exact pathophysiological mechanism of vitiligo remains elusive. However, several hypotheses, including autoimmune, oxidant-antioxidant, genetic susceptibility, neural and viral mechanisms, have been proposed to explain the selective destruction of melanocytes. Currently, clinical and bench findings suggest the major role of autoimmune factors in the progress of vitiligo. Inflammatory cells, mostly T lymphocytes, have been identified close to vitiligous skin lesion.2,3) Lesional CD8+ T cells specially induce melanocyte apoptosis in unaffected skin ex vivo, and the frequency of anti-melanocyte CD8+ T cells in both the blood and skin of vitiligo patients correlates with the severity of disease. 4,5) Moreover, immunosuppressive therapies targeting T-cell activation have been shown to be effective for vitiligo treatment.6,7) These evidences all support a direct role for T lymphocytes in melanocyte destruction in human vitiligo.Epigallocatechin-3-gallate (EGCG), a major catechin in green tea, is considered beneficial for human health, especially as an anti-oxidative agent.8) In addition, EGCG was confirmed to directly inhibit protein kinases by working as an ATP analog.9) Previously, we reported the therapeutic effect of EGCG in vitiligo induced by monobenzone in mice. 10) Our results suggested that it could contribute to the suppression of CD8+ T cell migration and the inflammatory cytokine expression. However, the mechanism regarding the EGCG regulation of immune responses in vitiligo is still unclear.The aim of study is to elucidate the inhibitory effects of EGCG on inflammatory signaling pathways and to identify the target of EGCG inhibition. RESULTS AND DISCUSSION EGCG Inhibited Janus Kinase (JAK)2 Activity in VitroThe JAKs are a family of four non-receptor tyrosine kinases including JAK1, JAK2 JAK3 and tyrosine kinase (TYK)2. Recruitment of stimuli to cell surface receptors activates JAKs which, in turn, phosphorylates and stimulates latent cytoplasmic signal transducer and activator of transcription (STAT) proteins to an active dimer, leading to nuclear translocation and DNA binding and subsequently modulating gene transcription.11) The JAK/STAT signal pathway controls a number of important biological responses, including immune functions, cellular growth, cell...

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Section: Egcg Inhibited Janus Kinase (Jak)2 Activity In Vitromentioning

confidence: 99%

Epigallocatechin-3-gallate (EGCG) Suppresses the Trafficking of Lymphocytes to Epidermal Melanocytes <i>via</i> Inhibition of JAK2: Its Implication for Vitiligo Treatment

Ning

Wang

Dong

et al. 2015

Biological & Pharmaceutical Bulletin

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“…There are additional JAK inhibitors undergoing investigation for the treatment of moderate-to-severe psoriasis [35], such as baricitinib (INCB-28050/LY3009104), a JAK1 and JAK3 inhibitor, that is being examined in a phase IIb dose ranging study [36].…”

Section: Jak Inhibitorsmentioning

confidence: 99%

Small molecules and antibodies for the treatment of psoriasis: a patent review (2010–2015)

Chiricozzi

Saraceno

Novelli

et al. 2016

Expert Opinion on Therapeutic Patents

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Though the recent introduction of new antipsoriatic agents has facilitated the management of long-term psoriasis, there is still a strong desire for alternative therapeutic options. Indeed, there remain unmet needs regarding safety and efficacy of psoriasis treatment that should be addressed. In this context, recently patented drugs may prove valid, interesting, and promising within the therapeutic paradigm.

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“…Tofacitinib, a pan JAK inhibitor with primary effect against JAK3, has been safely used for the treatment of rheumatoid arthritis, psoriasis and other conditions. 4,5 Its efficacy against lymphoma and its toxicity profile when used as combination therapy is still being evaluated. 6 The PET scan at the completion of the third cycle of GEM-OX with ofatumumab and tofacitinib showed a partial metabolic response with reduction in both disease size and FDG avidity ( Figure 2C).…”

Section: A B Cmentioning

confidence: 99%

A unique case of refractory primary mediastinal B-cell lymphoma with JAK3 mutation and the role for targeted therapy

et al. 2014

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Tofacitinib and Other Kinase Inhibitors in the Treatment of Psoriasis

Cited by 23 publications

References 24 publications

Epigallocatechin-3-gallate (EGCG) Suppresses the Trafficking of Lymphocytes to Epidermal Melanocytes <i>via</i> Inhibition of JAK2: Its Implication for Vitiligo Treatment

Epigallocatechin-3-gallate (EGCG) Suppresses the Trafficking of Lymphocytes to Epidermal Melanocytes <i>via</i> Inhibition of JAK2: Its Implication for Vitiligo Treatment

Small molecules and antibodies for the treatment of psoriasis: a patent review (2010–2015)

A unique case of refractory primary mediastinal B-cell lymphoma with JAK3 mutation and the role for targeted therapy

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