Literature DB >> 30249354

Discovery of potent and selective Spleen Tyrosine Kinase inhibitors for the topical treatment of inflammatory skin disease.

Michael D Barker1, John Liddle2, Francis L Atkinson2, David Matthew Wilson2, Marion C Dickson2, Cesar Ramirez-Molina2, Huw Lewis2, Rob P Davis2, Donald O Somers2, Margarete Neu2, Emma Jones2, Robert Watson2.   

Abstract

The discovery and lead optimisation of a novel series of SYK inhibitors is described. These were optimised for SYK potency and selectivity against Aurora B. Compounds were profiled in a human skin penetration study to identify a suitable candidate molecule for pre-clinical development. Compound 44 (GSK2646264) was selected for progression and is currently in Phase I clinical trials.
Copyright © 2018 Elsevier Ltd. All rights reserved.

Entities:  

Keywords:  Dermal; Inhibitor; Lead optimisation; SYK; Skin penetration; Spleen Tyrosine Kinase

Mesh：

Substances：

Year:  2018        PMID： 30249354     DOI： 10.1016/j.bmcl.2018.09.022

Source DB:  PubMed          Journal:  Bioorg Med Chem Lett        ISSN： 0960-894X            Impact factor:   2.823


  8 in total

1.  GSK2646264, a spleen tyrosine kinase inhibitor, attenuates the release of histamine in ex vivo human skin.

Authors:  Cesar Ramirez Molina; Sidsel Falkencrone; Per S Skov; Edward Hooper-Greenhill; Mike Barker; Marion C Dickson
Journal:  Br J Pharmacol       Date:  2019-03-21       Impact factor: 8.739

2.  A Comprehensive Approach to Urticaria: From Clinical Presentation to Modern Biological Treatments Through Pathogenesis.

Authors:  Marco Folci; Giacomo Ramponi; Enrico Brunetta
Journal:  Adv Exp Med Biol       Date:  2021       Impact factor: 2.622

Review 3.  Current and emerging treatments for chronic spontaneous urticaria.

Authors:  Kirti J Johal; Sarbjit S Saini
Journal:  Ann Allergy Asthma Immunol       Date:  2019-09-05       Impact factor: 6.347

Review 4.  Emerging Therapies in Chronic Spontaneous Urticaria.

Authors:  Taek Ki Min; Sarbjit S Saini
Journal:  Allergy Asthma Immunol Res       Date:  2019-07       Impact factor: 5.764

5.  Rapid Characterization of Chemical Components in Edible Mushroom Sparassis crispa by UPLC-Orbitrap MS Analysis and Potential Inhibitory Effects on Allergic Rhinitis.

Authors:  Zhixin Wang; Jingyu Liu; Xiangjian Zhong; Jinjie Li; Xin Wang; Linlin Ji; Xiaoya Shang
Journal:  Molecules       Date:  2019-08-20       Impact factor: 4.411

6.  Characterizing the structure-activity relationships of natural products, tanshinones, reveals their mode of action in inhibiting spleen tyrosine kinase.

Authors:  Min-Che Tung; Keng-Chang Tsai; Kit-Man Fung; Ming-Jaw Don; Tien-Sheng Tseng
Journal:  RSC Adv       Date:  2021-01-14       Impact factor: 3.361

Review 7.  Regulation of Trafficking and Signaling of the High Affinity IgE Receptor by FcεRIβ and the Potential Impact of FcεRIβ Splicing in Allergic Inflammation.

Authors:  Greer K Arthur; Glenn Cruse
Journal:  Int J Mol Sci       Date:  2022-01-12       Impact factor: 5.923

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

Authors:  Alex Walker; Lars Erwig; Katie Foster; Katherine Nevin; Joerg Wenzel; Margitta Worm; Nicola Williams; Nirav Ratia; Bao Hoang; Tanja Schneider-Merck; Sophie Gisbert; Heike Carnarius; Marion Dickson
Journal:  Exp Dermatol       Date:  2020-12-17       Impact factor: 3.960
  8 in total

北京卡尤迪生物科技股份有限公司 © 2022-2023.