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

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

  • Bioorg Med Chem Lett. 2018 Nov 15;28(21):3458-3462. doi: 10.1016/j.bmcl.2018.09.022.
Michael D Barker 1,  John Liddle 2,  Francis L Atkinson 2,  David Matthew Wilson 2,  Marion C Dickson 2,  Cesar Ramirez-Molina 2,  Huw Lewis 2,  Rob P Davis 2,  Donald O Somers 2,  Margarete Neu 2,  Emma Jones 2,  Robert Watson 2
Affiliations

Affiliations

  • 1 GlaxoSmithKline R&D, Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK. Electronic address: [email protected].
  • 2 GlaxoSmithKline R&D, Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK.
PMID: 30249354 DOI: 10.1016/j.bmcl.2018.09.022
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.

Keywords

Dermal; Inhibitor; Lead optimisation; SYK; Skin penetration; Spleen Tyrosine Kinase.

Figures
Products