GSK2646264 / GSK - LARVOL DELTA

Effects of a topical treatment with spleen tyrosine kinase (SYK) inhibitor in healthy subjects and patients with cold urticaria or chronic spontaneous urticaria: results of a Phase 1a/b randomised double-blind placebo-controlled study. (PubMed, Br J Clin Pharmacol) - "This Phase 1/1b study confirms that GSK2646264 cream applied topically penetrates the skin and some reduction in CTT was observed."

Clinical • Journal • P1 data • Chronic Spontaneous Urticaria • Dermatology • Urticaria • SYK

Safety, pharmacokinetics and pharmacodynamics of a topical SYK inhibitor in cutaneous lupus erythematosus: A double-blind Phase Ib study. (PubMed, Exp Dermatol) - "Similar findings were observed for CD3 + T cell and CD11c + dendritic cell levels; however, overall clinical activity remained unchanged with GSK2646264 vs. placebo. Further studies are warranted to assess SYK inhibitors as potential treatment for CLE."

Clinical • Journal • P1 data • PK/PD data • Cutaneous Lupus Erythematosus • Immunology • Inflammatory Arthritis • Lupus

Current and EmergingTreatments for Chronic Spontaneous Urticaria. (PubMed, Ann Allergy Asthma Immunol) - "The development of new treatments for CSU will importantly lead to improved options for patients and may assist with improving our understanding of disease pathophysiology."

Journal • Review • Dermatology • Urticaria

GSK2646264, a spleen tyrosine kinase inhibitor attenuates the release of histamine in ex vivo human skin. (PubMed, Br J Pharmacol) - "GSK2646264 administered topically or direct to the dermis blocked histamine release from in situ skin mast cells. A PK/PD relationship curve suggests that dermal concentrations above 6.8 μM should lead to approximately 90% inhibition of histamine release from skin mast cells following FcεRI activation implicating a potential use for the compound in skin mast cell diseases such as urticaria."

Journal • Preclinical • Cardiovascular • Dermatology • Dermatopathology • Immunology • Urticaria

Discovery of potent and selective Spleen Tyrosine Kinase inhibitors for the topical treatment of inflammatory skin disease. (PubMed, Bioorg Med Chem Lett) - "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."

Journal