Safety, pharmacokinetics and pharmacodynamics of a topical SYK inhibitor in cutaneous lupus erythematosus: A double-blind Phase Ib study

Autor: Joerg Wenzel, Sophie Gisbert, Alex Walker, Lars Erwig, Katie Foster, Katherine Nevin, Tanja Schneider-Merck, Heike Carnarius, Margitta Worm, Nicola Williams, Nirav Ratia, Marion C. Dickson, Bao Hoang

Publikováno v: Experimental Dermatology

The immunoregulator spleen tyrosine kinase (SYK) is upregulated in cutaneous lupus erythematosus (CLE). This double‐blind, multicentre, Phase Ib study evaluated the safety, tolerability, pharmacokinetics, pharmacodynamics and clinical efficacy of t

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::101882ae562739fac74a9a6039cfc474
https://pubmed.ncbi.nlm.nih.gov/33336508

Spleen tyrosine kinase (SYK) is a potential target for the treatment of cutaneous lupus erythematosus patients

Autor: Christine Braegelmann, Marion C. Dickson, Annegret Kuhn, Sandra Ferring-Schmitt, Nil Turan, Joerg Wenzel, Valerie J. Ludbrook, Sonja Sternberg, Thomas Bieber, Michael Hölzel

Publikováno v: Experimental Dermatology. 25:375-379

Spleen tyrosine kinase (SYK) is a protein kinase involved in cell proliferation and the regulation of inflammatory pathways. Due to the increasing evidence that kinase inhibitors have potential as specific anti-inflammatory drugs, we have investigate

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::40be060b00a6ea457ad2d6056ca04b60
https://doi.org/10.1111/exd.12986

A model of skin inflammation in humans leads to a rapid and reproducible increase in the interferon response signature: a potential translational model for drug development

Autor: Hayley Perry, Paul A. Wilson, Sam J. Garthside, Valerie J. Ludbrook, Michael Binks, Marion C. Dickson

Publikováno v: Inflammation Research. 64:171-183

To investigate Toll-like receptor activation in human skin using tape stripping and imiquimod cream challenges in healthy volunteers.Seventeen male Caucasian subjects underwent a baseline biopsy on their lower back prior to two tape stripping procedu

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cc49fb1eee1be966389b9128644da53c
https://doi.org/10.1007/s00011-015-0795-z

Safety, tolerability, efficacy and pharmacodynamics of the selective JAK1 inhibitor GSK2586184 in patients with systemic lupus erythematosus

Autor: Kirsty J. Hicks, L Kahl, M Layton, D Staumont-Sallé, D Machado, Stefano Zamuner, Michael Binks, Eric Hachulla, J Patel, Marion C. Dickson, R. van Vollenhoven, L Condreay, L Schifano, G Leon

Publikováno v: Lupus, 25(13), 1420-1430. SAGE Publications Ltd
Kahl, L, Patel, J, Layton, M, Binks, M, Hicks, K, Leon, L G, Hachulla, E, Machado, D, Staumont-Sallé, D, Dickson, M, Condreay, L, Schifano, L, Zamuner, S, van Vollenhoven, R F & JAK115919 Study Team 2016, ' Safety, tolerability, efficacy and pharmacodynamics of the selective JAK1 inhibitor GSK2586184 in patients with systemic lupus erythematosus ', Lupus, vol. 25, no. 13, pp. 1420-1430 . https://doi.org/10.1177/0961203316640910

We aimed to evaluate the pharmacodynamics, efficacy, safety and tolerability of the JAK1 inhibitor GSK2586184 in adults with systemic lupus erythematosus (SLE). In this adaptive, randomized, double-blind, placebo-controlled study, patients received o

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::858ce724a401c7edd4df0e690236bc09
https://research.vumc.nl/en/publications/d6c9043d-2d71-475f-b59e-3904bc19de1c

Discovery of GSK143, a highly potent, selective and orally efficacious spleen tyrosine kinase inhibitor

Autor: Philip Alan Skone, Donald O. Somers, Marion C. Dickson, Nick Smithers, Ann Louise Walker, Thomas George Christopher Hayhow, Stuart G. Leach, Karen Leavens, Clement Douault, Emma J. Jones, Dorothy Elwes, Robert J. Watson, Margarete Neu, Robert P. Davis, Matthew Gray, Neil Stuart Garton, Clare I. Hobbs, Alex Preston, Michael David Barker, Vipulkumar Kantibhai Patel, Cesar Ramirez-Molina, Paul S. Carter, Scott McCleary, Gordon G. Weingarten, Huw D. Lewis, Francis Louis Atkinson, John Liddle, Tracy Jane Shipley, Neil R. Curtis

Publikováno v: Bioorganic & Medicinal Chemistry Letters. 21:6188-6194

The lead optimisation of the diaminopyrimidine carboxamide series of spleen tyrosine kinase inhibitors is described. The medicinal chemistry strategy was focused on optimising the human whole blood activity whilst achieving a sufficient margin over l

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::58fce9afb90ca4e724d4726df2268b6f
https://doi.org/10.1016/j.bmcl.2011.07.082