Article
Biochemistry & Molecular Biology
Maxim Kondratyev, Vladimir R. Rudnev, Kirill S. Nikolsky, Alexander A. Stepanov, Denis Petrovsky, Liudmila Kulikova, Arthur T. Kopylov, Kristina A. Malsagova, Anna L. Kaysheva
Summary: Rheumatoid arthritis is a chronic autoimmune disease characterized by destructive synovitis and extra-articular manifestations. Cytokines play a role in the pathogenesis of rheumatoid arthritis by regulating inflammatory processes and inducing autoimmunity and chronic inflammation. Janus-associated kinase (JAK) and signal transducer and activator of transcription (STAT) proteins are involved in the development of autoimmune and inflammatory diseases. Small-molecule drugs that target JAK proteins are used for the treatment of rheumatoid arthritis. In this study, we investigated the interactions between the small-molecule drug ruxolitinib and JAK1 and JAK2 isoforms using molecular docking. Our results show that ruxolitinib selectively binds to JAK1 and JAK2 isoforms with high affinity, primarily through hydrophobic interactions. The specific amino acid residues responsible for the binding and retention of ruxolitinib were identified.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Medicine, General & Internal
Lise Torp Jensen, Kathrine E. Att, Marc Feldmann, Lars Fugger
Summary: JAK inhibitors have a broad impact on multiple cytokine pathways, making them highly effective in treating complex diseases. However, their broad reach also raises safety concerns, leading to a demand for more selective inhibitors. Deucravacitinib, as an allosteric TYK2 inhibitor, shows unprecedented functional selectivity and safety profile by targeting the regulatory pseudokinase domain of TYK2.
Article
Medicine, Research & Experimental
Misun Kim, Heung Joo Yuk, Yueun Min, Dong-Seon Kim, Yoon-Young Sung
Summary: Securinega suffruticosa extract attenuates atopic dermatitis and has potential as a therapeutic natural product candidate for AD.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Multidisciplinary Sciences
Katharina Boch, Soeren Draeger, Detlef Zillikens, Christoph Hudemann, Christoph M. Hammers, Sabrina Patzelt, Enno Schmidt, Ewan A. Langan, Ruediger Eming, Ralf J. Ludwig, Katja Bieber
Summary: Immunization with PV autoantigens induced non-pathogenic Dsg1/3 antibodies, but did not cause skin/mucous membrane disease in mice. These findings suggest that the induced autoantibodies were unable to bind to the conformational epitopes present in vivo.
Article
Medicine, Research & Experimental
Zhenpeng Dai, James Chen, Yuqian Chang, Angela M. Christiano
Summary: The study demonstrates that in the C3H/HeJ mouse model, JAK1-selective and JAK3-selective inhibitors can effectively induce hair regrowth and reduce AA-related inflammation, while JAK2-selective inhibitors show less efficacy.
Article
Pharmacology & Pharmacy
Xianbin Wang, Wenjun Cao, Chuanfen Sun, Yutie Wang, Mingyu Wang, Jiarong Wu
Summary: This study developed a pH-sensitive nanodrug, MTX@pH-AcDEX NPs, to decrease the toxicity of methotrexate (MTX) and enhance its therapeutic effect for rheumatoid arthritis (RA) treatment. The nanodrug showed notable pH-responsiveness and high drug loading. In vitro and in vivo experiments demonstrated reduced cytotoxicity and better anti-inflammatory effect compared to free MTX. Upon administration in an adjuvant-induced arthritis rat model, the nanodrug exhibited potent pharmacokinetic and pharmacodynamic profiles, accumulating in RA lesions and releasing MTX inhibitors for regulating the JAK-STAT pathways. These findings suggest the strong potential of the nanodrug for safe and effective RA therapy as well as other autoimmune diseases.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2022)
Article
Medicine, General & Internal
Faping Wang, Xiaoju Tang, Min Zhu, Hui Mao, Huajing Wan, Fengming Luo
Summary: JAKinibs are effective in improving symptoms of RA patients compared to placebo, but are associated with more adverse events. Baricitinib and upadacitinib have a higher risk of adverse events and infections, while only baricitinib is associated with a higher risk of herpes zoster.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Medicine, General & Internal
Brett King, Xingqi Zhang, Walter Gubelin Harcha, Jacek C. Szepietowski, Jerry Shapiro, Charles Lynde, Natasha A. Mesinkovska, Samuel H. Zwillich, Lynne Napatalung, Dalia Wajsbrot, Rana Fayyad, Amy Freyman, Debanjali Mitra, Vivek Purohit, Rodney Sinclair, Robert Wolk
Summary: This study investigated the efficacy and safety of Ritlecitinib, an oral medication, in patients with alopecia areata. The findings showed that Ritlecitinib had good efficacy and tolerability in patients aged 12 years and older with alopecia areata, making it a suitable treatment option for those who require systemic therapy.
Review
Medicine, General & Internal
Aikaterini Tsiogka, Maria Kyriazopoulou, George Kontochristopoulos, Electra Nicolaidou, Alexander Stratigos, Dimitris Rigopoulos, Stamatios Gregoriou
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)
Review
Medicine, Research & Experimental
Susmita Srivastava, Mahaboobkhan Rasool
Summary: IL-6 plays a significant role in inflammation and rheumatoid arthritis (RA), and excessive IL-6 negatively affects immune cells. Therapeutic strategies targeting IL-6 include antibodies and JAK inhibitors, but side effects are a concern.
Article
Rheumatology
Gustavo Citera, Rakesh Jain, Fedra Irazoque, Hugo Madariaga, David Gruben, Lisy Wang, Lori Stockert, Karina Santana, Abbas Ebrahim, Dario Ponce de Leon
Summary: The aim of this study was to assess the prevalence of major depressive disorder and generalized anxiety disorder in patients with rheumatoid arthritis (RA) and evaluate the efficacy of tofacitinib on RA symptoms. The results showed that the percentage of patients with these disorders decreased after 1 year of treatment with tofacitinib or adalimumab. Effective treatment of RA may lead to improvements in depression and anxiety symptoms.
RHEUMATOLOGY AND THERAPY
(2023)
Article
Multidisciplinary Sciences
Bridget S. Gosis, Shogo Wada, Chelsea Thorsheim, Kristina Li, Sunhee Jung, Joshua H. Rhoades, Yifan Yang, Jeffrey Brandimarto, Li Li, Kahealani Uehara, Cholsoon Jang, Matthew Lanza, Nathan B. Sanford, Marc R. Bornstein, Sunhye Jeong, Paul M. Titchenell, Sudha B. Biddinger, Zoltan Arany
Summary: Selective inhibition of mTORC1 signaling in mice promotes activation of transcription factor E3 (TFE3) in the liver, protecting against NAFLD and NASH. TFE3 induces lipid consumption and suppresses anabolic lipogenesis, inhibiting lipogenesis by interacting with SREBP-1c on chromatin.
Article
Multidisciplinary Sciences
Haibin Zhou, Jianfeng Lu, Krishnapriya Chinnaswamy, Jeanne A. Stuckey, Liu Liu, Donna McEachern, Chao-Yie Yang, Denzil Bernard, Hong Shen, Liangyou Rui, Yi Sun, Shaomeng Wang
Summary: The study identifies two potent and selective covalent DCN1 inhibitors that selectively inhibit cullin-3 neddylation in cells, leading to increased NRF2 protein levels and protection of mice from liver damage.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Maurizio Benucci, Francesca Li Gobbi, Paola Fusi, Arianna Damiani, Edda Russo, Serena Guiducci, Mariangela Manfredi, Valentina Grossi, Maria Infantino, Amedeo Amedei
Summary: The aim of this study was to determine additional disease activity biomarkers in RA patients receiving selective JAK-1 inhibitors. The study found that suPAR and cCLP levels may guide different treatment choices between UPA and FIL.
FRONTIERS IN BIOSCIENCE-LANDMARK
(2023)
Article
Microbiology
Jiah Yeom, Dong Joon Yim, Seongho Ma, Young-Hee Lim
Summary: P. freudenreichii MJ2 inhibits osteoclast differentiation and improves rheumatoid arthritis in both in vitro and in vivo studies. Live and dead MJ2 showed similar therapeutic effects in the arthritis model.
Article
Biochemistry & Molecular Biology
Jean-Baptiste Telliez, Martin E. Dowty, Lu Wang, Jason Jussif, Tsung Lin, Li Li, Erick Moy, Paul Balbo, Wei Li, Yajuan Zhao, Kimberly Crouse, Caitlyn Dickinson, Peter Symanowicz, Martin Hegen, Mary Ellen Banker, Fabien Vincent, Ray Unwalla, Sidney Liang, Adam M. Gilbert, Matthew F. Brown, Matthew Hayward, Justin Montgomery, Xin Yang, Jonathan Bauman, John I. Trujillo, Agustin Casimiro-Garcia, Felix F. Vajdos, Louis Leung, Kieran F. Geoghegan, Amira Quazi, Dejun Xuan, Lyn Jones, Erik Hett, Katherine Wright, James D. Clark, Atli Thorarensen
ACS CHEMICAL BIOLOGY
(2016)
Article
Biochemistry & Molecular Biology
Sara Mostafavi, Hideyuki Yoshida, Devapregasan Moodley, Hugo LeBoite, Katherine Rothamel, Towfique Raj, Chun Jimmie Ye, Nicolas Chevrier, Shen-Ying Zhang, Ting Feng, Mark Lee, Jean-Laurent Casanova, James D. Clark, Martin Hegen, Jean-Baptiste Telliez, Nir Hacohen, Philip L. De Jager, Aviv Regev, Diane Mathis, Christophe Benoist
Article
Allergy
James Krueger, James D. Clark, Mayte Suarez-Farinas, Judilyn Fuentes-Duculan, Inna Cueto, Claire Q. Wang, Huaming Tan, Robert Wolk, Scott T. Rottinghaus, Maryann Z. Whitley, Hernan Valdez, David von Schack, Shawn P. O'Neil, Padmalatha S. Reddy, Svitlana Tatulych
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2016)
Article
Multidisciplinary Sciences
Devapregasan Moodley, Hideyuki Yoshida, Sara Mostafavi, Natasha Asinovski, Adriana Ortiz-Lopez, Peter Symanowicz, Jean-Baptiste Telliez, Martin Hegen, James D. Clark, Diane Mathis, Christophe Benoist
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2016)
Article
Immunology
Kent J. Weinhold, Jack F. Bukowski, Todd V. Brennan, Robert J. Noveck, Janet S. Staats, Liwen Lin, Linda Stempora, Constance Hammond, Ann Wouters, Christopher F. Mojcik, John Cheng, Mark Collinge, Michael I. Jesson, Anasuya Hazra, Pinaki Biswas, Shuping Lan, James D. Clark, Jennifer A. Hodge
CLINICAL IMMUNOLOGY
(2018)
Article
Chemistry, Medicinal
Michael L. Vazquez, Neelu Kaila, Joseph W. Strohbach, John D. Trzupek, Matthew F. Brown, Mark E. Flanagan, Mark J. Mitton-Fry, Timothy A. Johnson, Ruth E. TenBrink, Eric P. Arnold, Arindrajit Basak, Steven E. Heasley, Soojin Kwon, Jonathan Langille, Mihir D. Parikh, Sarah H. Griffin, Jeffrey M. Casavant, Brian A. Duclos, Ashley E. Fenwick, Thomas M. Harris, Seungil Han, Nicole Caspers, Martin E. Dowty, Xin Yang, Mary Ellen Banker, Martin Hegen, Peter T. Symanowicz, Li Li, Lu Wang, Tsung H. Lin, Jason Jussif, James D. Clark, Jean-Baptiste Telliez, Ralph P. Robinson, Ray Unwalla
JOURNAL OF MEDICINAL CHEMISTRY
(2018)
Article
Dermatology
B. Strober, M. Buonanno, J. D. Clark, T. Kawabata, H. Tan, R. Wolk, H. Valdez, R. G. Langley, J. Harness, A. Menter, K. Papp
BRITISH JOURNAL OF DERMATOLOGY
(2013)
Article
Immunology
Paresh Thakker, Suzana Marusic, Nancy L. Stedman, Katherine L. Lee, John C. McKew, Andrew Wood, Samuel J. Goldman, Michael W. Leach, Mary Collins, Vijay K. Kuchroo, Stanley F. Wolf, James D. Clark, Mina Hassan-Zahraee
JOURNAL OF IMMUNOLOGY
(2011)
Article
Chemistry, Medicinal
James D. Clark, Mark E. Flanagan, Jean-Baptiste Telliez
JOURNAL OF MEDICINAL CHEMISTRY
(2014)
Article
Chemistry, Medicinal
Andrew Fensome, Catherine M. Ambler, Eric Arnold, Mary Ellen Banker, Matthew F. Brown, Jill Chrencik, James D. Clark, Martin E. Dowty, Ivan V. Efremov, Andrew Flick, Brian S. Gerstenberger, Ariamala Gopalsamy, Matthew M. Hayward, Martin Hegen, Brett D. Hollingshead, Jason Jussif, John D. Knafels, David C. Limburg, David Lin, Tsung H. Lin, Betsy S. Pierce, Eddine Saiah, Raman Sharma, Peter T. Symanowicz, Jean-Baptiste Telliez, John I. Trujillo, Felix F. Vajdos, Fabien Vincent, Zhao-Kui Wan, Li Xing, Xiaojing Yang, Xin Yang, Liying Zhang
JOURNAL OF MEDICINAL CHEMISTRY
(2018)
Article
Rheumatology
Maria Seddighzadeh, Antonio Gonzalez, Bo Ding, Aida Ferreiro-Iglesias, Juan J. Gomez-Reino, Lars Klareskog, Lars Alfredsson, Kyri Dunussi-Joannopoulos, James D. Clark, Leonid Padyukov
JOURNAL OF RHEUMATOLOGY
(2012)
Article
Genetics & Heredity
Marcus Ronninger, Yongjing Guo, Klementy Shchetynsky, Andrew Hill, Mohsen Khademi, Tomas Olsson, Padmalatha S. Reddy, Maria Seddighzadeh, James D. Clark, Lih-Ling Lin, Margot O'Toole, Leonid Padyukov
Article
Rheumatology
Ronald van Vollenhoven, Eun Bong Lee, Sander Strengholt, Christopher Mojcik, Hernan Valdez, Sriram Krishnaswami, Pinaki Biswas, Irina Lazariciu, Anasuya Hazra, James D. Clark, Jennifer Hodge, Lisy Wang, Ernest Choy
ARTHRITIS & RHEUMATOLOGY
(2019)
Review
Rheumatology
J. A. Hodge, T. T. Kawabata, S. Krishnaswami, J. D. Clark, J. -B. Telliez, M. E. Dowty, S. Menon, M. Lamba, S. Zwillich
CLINICAL AND EXPERIMENTAL RHEUMATOLOGY
(2016)
Article
Pharmacology & Pharmacy
Christopher A. Hewson, Sheena Patel, Luigino Calzetta, Hinnah Campwala, Suzanne Havard, Emma Luscombe, Philip A. Clarke, Peter T. Peachell, Maria G. Matera, Mario Cazzola, Clive Page, William M. Abraham, Cara M. Williams, James D. Clark, Wai L. Liu, Nicholas P. Clarke, Michael Yeadon
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2012)