☆ 4.5 Review

New small molecules in dermatology: for the autoimmunity, inflammation and beyond

INFLAMMATION RESEARCH (2023)

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Article Dermatology

Efficacy and safety of oral ritlecitinib for the treatment of active nonsegmental vitiligo: A randomized phase 2b clinical trial

Khaled Ezzedine et al.

Summary: This study evaluated the efficacy and safety of oral JAK3/TEC inhibitor ritlecitinib in patients with active nonsegmental vitiligo. The results showed that ritlecitinib demonstrated significant efficacy and good tolerability in treating vitiligo.

JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY (2023)

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Article Dermatology

Deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: Efficacy and safety results from the 52-week, randomized, double-blinded, placebo-controlled phase 3 POETYK PSO-1 trial

April W. Armstrong et al.

Summary: This study compared the efficacy and safety of deucravacitinib with placebo and apremilast in adults with moderate to severe plaque psoriasis. The results showed that deucravacitinib was more effective than placebo and apremilast in reducing symptoms and improving skin lesions, and the adverse event rates were similar among the three drugs.

JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY (2023)

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Article Dermatology

Targeted Therapy and Immunotherapy in Melanoma

Jake Lazaroff et al.

DERMATOLOGIC CLINICS (2023)

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Article Rheumatology

Effect of JAK inhibitors on high- and low-density lipoprotein in patients with rheumatoid arthritis: a systematic review and network meta-analysis

Na Li et al.

Summary: This study systematically reviewed and analyzed the effects of JAK inhibitors on HDL and LDL levels in RA patients. The results showed that all five JAK inhibitors led to an increase in HDL and LDL levels, but did not significantly affect cardiovascular disease risk.

CLINICAL RHEUMATOLOGY (2022)

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Review Dermatology

JAK-inhibitors in dermatology - small molecules, big impact? Overview of the mechanism of action, previous study results and potential adverse effects

Benjamin Klein et al.

Summary: JAK inhibitors have shown promising results in treating various chronic inflammatory skin diseases through their ability to target proinflammatory cytokines released via the JAK-STAT pathway. Recent approvals of JAK inhibitors like Baricitinib, Upadacitinib, and Abrocitinib offer new systemic therapeutic options for moderate to severe atopic dermatitis patients. While these small molecules have demonstrated effectiveness, potential side effects and necessary laboratory examinations should be carefully considered.

JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT (2022)

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Article Multidisciplinary Sciences

Adverse events associated with JAK inhibitors in 126,815 reports from the WHO pharmacovigilance database

Lea Hoisnard et al.

Summary: This retrospective observational study assessed the safety of the first three approved Janus kinase (JAK) inhibitors: ruxolitinib, tofacitinib, and baricitinib. The study found significant associations between these drugs and infectious adverse events, musculoskeletal and connective tissue disorders, embolism and thrombosis, and neoplasms. Tofacitinib was also associated with gastrointestinal perforation events. However, there was no significant increase in major cardiovascular events.

SCIENTIFIC REPORTS (2022)

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Review Medicine, General & Internal

Bruton's Kinase Inhibitors for the Treatment of Immunological Diseases: Current Status and Perspectives

Ewa Robak et al.

Summary: The use of Bruton's tyrosine kinase (BTK) inhibitors has revolutionized the treatment of patients with B-cell lymphoid malignancies. These inhibitors have also shown promising results in immune-mediated diseases. This review article provides a comprehensive overview of the preclinical and clinical evidence supporting the role of BTK inhibitors in various autoimmune, allergic, and inflammatory conditions.

JOURNAL OF CLINICAL MEDICINE (2022)

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Review Pharmacology & Pharmacy

A Comprehensive Overview of Globally Approved JAK Inhibitors

Ahmed M. Shawky et al.

Summary: This review discusses eleven JAK inhibitors that have been approved for clinical use, including their chemical and pharmacological data, inhibitory activities, pharmacological uses, crystal structures, and metabolic pathways and metabolites. This information can contribute to the design of new JAK inhibitors for the treatment of inflammatory and autoimmune diseases.

PHARMACEUTICS (2022)

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Article Dermatology

JAK in the [Black] Box: A Dermatology Perspective on Systemic JAK Inhibitor Safety

Sarina B. Elmariah et al.

Summary: JAK inhibitors have broad potential for use in dermatology, but recent data show increased risk of adverse cardiovascular events and venous thromboembolism. Despite their effectiveness in treating psoriatic arthritis and atopic dermatitis, balancing the potential benefits with the low-absolute risk safety concerns is crucial.

AMERICAN JOURNAL OF CLINICAL DERMATOLOGY (2022)

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Letter Dermatology

Phase 2 BELIEVE study part B: Efficacy and safety of rilzabrutinib for patients with pemphigus vulgaris

D. F. Murrell et al.

JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY (2022)

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Review Immunology

Pathophysiological Role of Nucleic Acid-Sensing Pattern Recognition Receptors in Inflammatory Diseases

Norisuke Kano et al.

Summary: This review focuses on the role of PRRs in recognizing nucleic acids and their pathophysiological roles in various inflammatory diseases.

FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY (2022)

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Review Medicine, General & Internal

The JAK/STAT Pathway and Its Selective Inhibition in the Treatment of Atopic Dermatitis: A Systematic Review

Aikaterini Tsiogka et al.

Summary: In recent years, the understanding of the pathogenesis of atopic dermatitis (AD) has expanded, leading to the development of novel therapeutic molecules that target the core inflammatory components of the disease. The Janus kinase (JAK)/signal transducer and activation of transcription (STAT) pathway is involved in intracellular signal transduction and gene transcription regulation. The activation of T-helper (Th)-2 and Th22 immune responses plays a pivotal role in the immunopathogenesis of AD, followed by a variable degree of Th1 and Th17 activation. JAK inhibitors have emerged as a potential treatment option for AD due to their ability to inhibit the signal transduction of inflammatory cytokines.

JOURNAL OF CLINICAL MEDICINE (2022)

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Article Biochemistry & Molecular Biology

From magic bullets to modern therapeutics: Paul Ehrlich, the German immunobiologist and physician coined the term 'complement'

Peter F. Zipfel et al.

Summary: Paul Ehrlich, a pioneering immunobiologist and physician, coined the term 'complement' and made substantial contributions to immunobiology and medicine. His work on immunity led to the identification of complement and he was awarded the Nobel Prize in 1908. He also played a role in the diagnosis and treatment of complement-mediated diseases.

MOLECULAR IMMUNOLOGY (2022)

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Article Immunology

Translational autoimmunity in pemphigus and the role of novel Bruton tyrosine kinase inhibitors

Piyu Parth Naik

Summary: This review discusses the role of BTK in the treatment of pemphigus and highlights the potential of BTK inhibitors as promising therapeutic targets for pemphigus.

JOURNAL OF TRANSLATIONAL AUTOIMMUNITY (2022)

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Article Pharmacology & Pharmacy

Phase 1 study in healthy participants of the safety, pharmacokinetics, and pharmacodynamics of enpatoran (M5049), a dual antagonist of toll-like receptors 7 and 8

Andreas Port et al.

Summary: This study evaluated the safety, pharmacokinetics, and pharmacodynamics of a new toll-like receptor 7 and 8 dual antagonist, enpatoran, in healthy participants. Results indicated that enpatoran was well tolerated at both single and multiple oral doses, with inhibitory effects on interleukin-6 secretion. Further investigation of enpatoran is warranted for potential treatment of diseases driven by TLR7/8 overactivation.

PHARMACOLOGY RESEARCH & PERSPECTIVES (2021)

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Review Biochemistry & Molecular Biology

The Development of BTK Inhibitors: A Five-Year Update

Bruno Tasso et al.

Summary: BTK has been a significant target for therapeutic agents in cancer and autoimmune disorders, with both irreversible and reversible inhibitors being developed and investigated. Research on BTK function and inhibitors is of interest for pharmaceutical companies and academia.

MOLECULES (2021)

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Letter Dermatology

Topical tofacitinib for the treatment of alopecia areata affecting facial hair

K. L. S. Kerkemeyer et al.

BRITISH JOURNAL OF DERMATOLOGY (2021)

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Article Dermatology

Proof of concept for the clinical effects of oral rilzabrutinib, the first Bruton tyrosine kinase inhibitor for pemphigus vulgaris: the phase II BELIEVE study

D. F. Murrell et al.

Summary: Rilzabrutinib demonstrated promising efficacy and safety in the treatment of pemphigus patients, reducing the need for corticosteroids and showing potential as a new treatment strategy.

BRITISH JOURNAL OF DERMATOLOGY (2021)

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Article Dermatology

A phase 2a randomized, placebo-controlled study to evaluate the efficacy and safety of the oral Janus kinase inhibitors ritlecitinib and brepocitinib in alopecia areata: 24-week results

Brett King et al.

Summary: The study evaluated the efficacy and safety of two Janus kinase inhibitors, Ritlecitinib and Brepocitinib, in patients with alopecia areata, showing promising results in improving hair loss. However, two patients in the Brepocitinib group experienced serious adverse events.

JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY (2021)

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Review Biochemistry & Molecular Biology

Btk Inhibitors: A Medicinal Chemistry and Drug Delivery Perspective

Chiara Brullo et al.

Summary: In recent years, Btk inhibitors have emerged as a new target in medicinal chemistry, with reversible compounds being developed to overcome the limitations of irreversible inhibitors. Clinical trials and preclinical investigations have been conducted for malignancies, chronic inflammation conditions, and SARS-CoV-2 infection. Nanoformulations are also being studied to increase the bioavailability of ibrutinib.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Review Allergy

JAK inhibitors in the treatment of atopic dermatitis

Raj Chovatiya et al.

Summary: Atopic dermatitis (AD) is a chronic inflammatory skin disorder with limited treatment options. Recent studies have shown that both topical and systemic Janus kinase (JAK) inhibitors hold promise in treating AD, with further research needed to fully understand their efficacy and safety.

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY (2021)

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Article Dermatology

Selectivity Profile of the Tyrosine Kinase 2 Inhibitor Deucravacitinib Compared with Janus Kinase 1/2/3 Inhibitors

Anjaneya Chimalakonda et al.

Summary: Psoriasis is a chronic inflammatory skin condition that affects patients' physical health and well-being. Deucravacitinib, a new oral drug, selectively inhibits TYK2 in the treatment of psoriasis, showing distinct characteristics from JAK inhibitors.

DERMATOLOGY AND THERAPY (2021)

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Review Biochemistry & Molecular Biology

The JAK/STAT signaling pathway: from bench to clinic

Xiaoyi Hu et al.

Summary: The JAK/STAT signaling pathway is a crucial cellular signal transduction pathway, associated with various cancers and autoimmune diseases. Researchers discussed the composition, activation, and regulation of this pathway, as well as its role in diseases.

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2021)

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Review Biochemistry & Molecular Biology

Targeting MAPK Signaling in Cancer: Mechanisms of Drug Resistance and Sensitivity

Shannon Lee et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2020)

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Article Chemistry, Medicinal

Discovery of LOU064 (Remibrutinib), a Potent and Highly Selective Covalent Inhibitor of Bruton's Tyrosine Kinase

Daniela Angst et al.

JOURNAL OF MEDICINAL CHEMISTRY (2020)

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Review Medicine, Research & Experimental

ERK/MAPK signalling pathway and tumorigenesis

Yan-Jun Guo et al.

EXPERIMENTAL AND THERAPEUTIC MEDICINE (2020)

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Review Pharmacology & Pharmacy

Small molecules targeting the innate immune cGAS-STING-TBK1 signaling pathway

Chunyong Ding et al.

ACTA PHARMACEUTICA SINICA B (2020)

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Article Medicine, General & Internal

Selumetinib in Children with Inoperable Plexiform Neurofibromas

Andrea M. Gross et al.

NEW ENGLAND JOURNAL OF MEDICINE (2020)

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Review Oncology

Targeting Alterations in the RAF-MEK Pathway

Rona Yaeger et al.

CANCER DISCOVERY (2019)

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Article Immunology

Efficacy and Pharmacodynamic Modeling of the BTK Inhibitor Evobrutinib in Autoimmune Disease Models

Philipp Haselmayer et al.

JOURNAL OF IMMUNOLOGY (2019)

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Review Pharmacology & Pharmacy

JAK3-selective inhibitor peficitinib for the treatment of rheumatoid arthritis

Qian Qiu et al.

EXPERT REVIEW OF CLINICAL PHARMACOLOGY (2019)

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Article Chemistry, Medicinal

Highly Selective Inhibition of Tyrosine Kinase 2 (TYK2) for the Treatment of Autoimmune Diseases: Discovery of the Allosteric Inhibitor BMS-986165

Stephen T. Wrobleski et al.

JOURNAL OF MEDICINAL CHEMISTRY (2019)

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Article Immunology

Role of Src and Cortactin in Pemphigus Skin Blistering

Daniela Kugelmann et al.

FRONTIERS IN IMMUNOLOGY (2019)

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Article Chemistry, Medicinal

Discovery of Evobrutinib: An Oral, Potent, and Highly Selective, Covalent Bruton's Tyrosine Kinase (BTK) Inhibitor for the Treatment of Immunological Diseases

Richard D. Caldwell et al.

JOURNAL OF MEDICINAL CHEMISTRY (2019)

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Review Immunology

Tyrosine Kinases in Autoimmune and Inflammatory Skin Diseases

Kata P. Szilveszter et al.

FRONTIERS IN IMMUNOLOGY (2019)

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Review Immunology

Emerging Topical and Systemic JAK Inhibitors in Dermatology

Farzan Solimani et al.

FRONTIERS IN IMMUNOLOGY (2019)

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Review Dermatology

Are neutrophilic dermatoses autoinflammatory disorders?

T. K. Satoh et al.

BRITISH JOURNAL OF DERMATOLOGY (2018)

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Article Medicine, Research & Experimental

γδTCR recruits the Syk/PI3K axis to drive proinflammatory differentiation program

Ryunosuke Muro et al.

JOURNAL OF CLINICAL INVESTIGATION (2018)

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Review Pharmacology & Pharmacy

BRAF and MEK Inhibitors: Use and Resistance in BRAF-Mutated Cancers

Jaquelyn N. Sanchez et al.

DRUGS (2018)

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Letter Dermatology

Topical 2% tofacitinib for children with alopecia areata, alopecia totalis, and alopecia universalis

Elana Putterman et al.

JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY (2018)

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Article Pharmacology & Pharmacy

Usage of Mitogen-Activated Protein Kinase Small Molecule Inhibitors: More Than Just Inhibition!

Steffen K. Meurer et al.

FRONTIERS IN PHARMACOLOGY (2018)

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Article Immunology

Whole-genome expression Profiling in skin reveals sYK as a Key regulator of inflammation in experimental epidermolysis Bullosa acquisita

Unni K. Samavedam et al.

FRONTIERS IN IMMUNOLOGY (2018)

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Article Immunology

Cutting Edge: Dysregulated CARD9 Signaling in Neutrophils Drives Inflammation in a Mouse Model of Neutrophilic Dermatoses

Sarang Tartey et al.

JOURNAL OF IMMUNOLOGY (2018)

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Article Dermatology

The Syk Tyrosine Kinase Is Required for Skin Inflammation in an In Vivo Mouse Model of Epidermolysis Bullosa Acquisita

Tamas Nemeth et al.

JOURNAL OF INVESTIGATIVE DERMATOLOGY (2017)

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Review Dermatology

JAK inhibitors in dermatology: The promise of a new drug class

William Damsky et al.

JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY (2017)

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Review Biotechnology & Applied Microbiology

JAK inhibition as a therapeutic strategy for immune and inflammatory diseases

Daniella M. Schwartz et al.

NATURE REVIEWS DRUG DISCOVERY (2017)

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Review Biochemistry & Molecular Biology

Mitogen-activated Protein Kinase (MAPK) Interacting Kinases 1 and 2 (MNK1 and MNK2) as Targets for Cancer Therapy: Recent Progress in the Development of MNK Inhibitors

Agnieszka Dreas et al.

CURRENT MEDICINAL CHEMISTRY (2017)

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Article Oncology

Gene Expression Profiling in BRAF-Mutated Melanoma Reveals Patient Subgroups with Poor Outcomes to Vemurafenib That May Be Overcome by Cobimetinib Plus Vemurafenib

Matthew J. Wongchenko et al.

CLINICAL CANCER RESEARCH (2017)

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Review Cell Biology

The role of JAK-STAT signaling pathway and its regulators in the fate of T helper cells

Farhad Seif et al.

CELL COMMUNICATION AND SIGNALING (2017)

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Review Immunology

Bullous pemphigoid

Isin Sinem Bagci et al.

AUTOIMMUNITY REVIEWS (2017)

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Review Oncology

Combination Treatment of Patients with BRAF-Mutant Melanoma: A New Standard of Care

Ester Simeone et al.

BIODRUGS (2017)

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Review Immunology

The role of Bruton's tyrosine kinase in autoimmunity and implications for therapy

Leslie J. Crofford et al.

EXPERT REVIEW OF CLINICAL IMMUNOLOGY (2016)

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Review Immunology

Tyrosine kinase signaling pathways in neutrophils

Krisztina Futosi et al.

IMMUNOLOGICAL REVIEWS (2016)

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Review Oncology

Targeting drivers of melanoma with synthetic small molecules and phytochemicals

Leah Ray Strickland et al.

CANCER LETTERS (2015)

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Review Pharmacology & Pharmacy

Src protein-tyrosine kinase structure, mechanism, and small molecule inhibitors

Robert Roskoski

PHARMACOLOGICAL RESEARCH (2015)

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Article Pathology

Fcγ Receptors HI and IV Mediate Tissue Destruction in a Novel Adult Mouse Model of Bullous Pemphigoid

Franziska S. Schulze et al.

AMERICAN JOURNAL OF PATHOLOGY (2014)

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Article Immunology

The Src family kinases Hck, Fgr, and Lyn are critical for the generation of the in vivo inflammatory environment without a direct role in leukocyte recruitment

Miklos Kovacs et al.

JOURNAL OF EXPERIMENTAL MEDICINE (2014)

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Article Medicine, General & Internal

Combined Vemurafenib and Cobimetinib in BRAF-Mutated Melanoma

James Larkin et al.

NEW ENGLAND JOURNAL OF MEDICINE (2014)

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Review Oncology

Targeting MAPK pathway in melanoma therapy

Yabin Cheng et al.

CANCER AND METASTASIS REVIEWS (2013)

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Article Medicine, Research & Experimental

MEK inhibition exhibits efficacy in human and mouse neurofibromatosis tumors

Walter J. Jessen et al.

JOURNAL OF CLINICAL INVESTIGATION (2013)

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Article Medicine, General & Internal

Pemphigoid diseases

Enno Schmidt et al.

LANCET (2013)

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Article Chemistry, Medicinal

Discovery of Dabrafenib: A Selective Inhibitor of Raf Kinases with Antitumor Activity against B-Raf-Driven Tumors

Tara R. Rheault et al.

ACS MEDICINAL CHEMISTRY LETTERS (2013)

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Review Pharmacology & Pharmacy

Targeting Src family kinases in anti-cancer therapies: turning promise into triumph

Siyuan Zhang et al.

TRENDS IN PHARMACOLOGICAL SCIENCES (2012)

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Article Biotechnology & Applied Microbiology

Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity

Theonie Anastassiadis et al.

NATURE BIOTECHNOLOGY (2011)

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Article Rheumatology

The Bruton tyrosine kinase inhibitor PCI-32765 ameliorates autoimmune arthritis by inhibition of multiple effector cells

Betty Y. Chang et al.

ARTHRITIS RESEARCH & THERAPY (2011)

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Article Multidisciplinary Sciences

Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma

Gideon Bollag et al.

NATURE (2010)

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Review Immunology

The SYK tyrosine kinase: a crucial player in diverse biological functions

Attila Mocsai et al.

NATURE REVIEWS IMMUNOLOGY (2010)

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Review Biochemistry & Molecular Biology

Tyrosine Kinase Inhibitors - A Review on Pharmacology, Metabolism and Side Effects

Joerg Thomas Hartmann et al.

CURRENT DRUG METABOLISM (2009)

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Review Immunology

Janus kinases in immune cell signaling

Kamran Ghoreschi et al.

IMMUNOLOGICAL REVIEWS (2009)

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Article Oncology

Src activation in melanoma and Src inhibitors as therapeutic agents in melanoma

Jade Homsi et al.

MELANOMA RESEARCH (2009)

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Article Rheumatology

An orally bioavailable spleen tyrosine kinase inhibitor delays disease progression and prolongs survival in murine lupus

Frances Rena Bahjat et al.

ARTHRITIS AND RHEUMATISM (2008)

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Article Immunology

Differential Expression and Molecular Associations of Syk in Systemic Lupus Erythematosus T Cells

Sandeep Krishnan et al.

JOURNAL OF IMMUNOLOGY (2008)

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Article Oncology

Inhibition of Src Family Kinases with Dasatinib Blocks Migration and Invasion of Human Melanoma Cells

Ralf Buettner et al.

MOLECULAR CANCER RESEARCH (2008)

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Review Cell Biology

Canonical and non-canonical JAK-STAT signaling

Willis X. Li

TRENDS IN CELL BIOLOGY (2008)

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Review Cell Biology

Immunoreceptor-like signaling by β2 and β3 integrins

Zoltan Jakus et al.

TRENDS IN CELL BIOLOGY (2007)

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Article Immunology

Syk- and CARD9-dependent coupling of innate immunity to the induction of T helper cells that produce interleukin 17

Salome LeibundGut-Landmann et al.

NATURE IMMUNOLOGY (2007)

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Review Pharmacology & Pharmacy

The Src signaling pathway: a potential target in melanoma and other malignancies

Jade Homsi et al.

EXPERT OPINION ON THERAPEUTIC TARGETS (2007)

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Article Immunology

Integrin signaling in neutrophils and macrophages uses adaptors containing immunoreceptor tyrosine-based activation motifs

Attila Mocsai et al.

NATURE IMMUNOLOGY (2006)

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Review Medicine, General & Internal

Pemphigus, bullous impetigo, and the staphylococcal scalded-skin syndrome

John R. Stanley et al.

NEW ENGLAND JOURNAL OF MEDICINE (2006)

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Article Immunology

Role of FcRs in animal model of autoimmune bullous pemphigoid

Minglang Zhao et al.

JOURNAL OF IMMUNOLOGY (2006)

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Review Biochemistry & Molecular Biology

Src-family kinases: rheostats of immune cell signaling

CA Lowell

MOLECULAR IMMUNOLOGY (2004)

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Review Oncology

A renaissance for SRC

TJ Yeatman

NATURE REVIEWS CANCER (2004)

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Review Biochemistry & Molecular Biology

Src family kinases, key regulators of signal transduction

SJ Parsons et al.

ONCOGENE (2004)

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Review Biochemistry & Molecular Biology

Crosstalk between steroid receptors and the c-Src-receptor tyrosine kinase pathways: implications for cell proliferation

MA Shupnik

ONCOGENE (2004)

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Article Multidisciplinary Sciences

Regulation of blood and lymphatic vascular separation by signaling proteins SLP-76 and Syk

F Abtahian et al.

SCIENCE (2003)

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Article Immunology

Syk is required for integrin signaling in neutrophils

A Mócsai et al.

IMMUNITY (2002)

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Review Multidisciplinary Sciences

Oncogenic kinase signalling

P Blume-Jensen et al.

NATURE (2001)

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Article Medicine, Research & Experimental

Antibodies against keratinocyte antigens other than desmogleins 1 and 3 can induce pemphigus vulgaris-like lesions

VT Nguyen et al.

JOURNAL OF CLINICAL INVESTIGATION (2000)

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