First-in-Human Study for a Selective Rearranged During Transfection Tyrosine Kinase Inhibitor, GSK3352589, to Investigate the Safety, Tolerability, and Pharmacokinetics in Healthy Volunteers.

Rearranged during transfection (RET), a neuronal growth factor receptor tyrosine kinase, regulates the development of sympathetic, parasympathetic, motor, and sensory neurons in the enteric nervous system. The intended site of action for GSK3352589 is intestinal tissues. GSK3352589 is an RET kinase inhibitor that was administered in double-blind, randomized, placebo-controlled single-dose (SD) and repeat-dose (RD) studies in healthy subjects to investigate its safety/tolerability and pharmacokinetics.

A Phase 1 Randomized, Placebo-Controlled Trial With a Topical Inhibitor of Stearoyl-Coenzyme A Desaturase 1 Under Occluded and Nonoccluded Conditions.

Stearoyl-coenzyme A desaturase 1 (SCD-1) in sebaceous glands is a key enzyme in the synthesis of monounsaturated fatty acids essential for acne development. GSK1940029 gel, a novel SCD-1 inhibitor, is being developed as a potential treatment for acne. To assess the irritation potential, pharmacokinetics (PK), and safety of topical GSK1940029 to the skin of healthy adults, two interdependent studies were conducted in parallel.

First-in-Human Studies for a Selective RET Tyrosine Kinase Inhibitor, GSK3179106, to Investigate the Safety, Tolerability, and Pharmacokinetics in Healthy Volunteers.

Rearranged during transfection (RET), a neuronal growth factor receptor tyrosine kinase, regulates the development of the sympathetic, parasympathetic, motor, and sensory neurons in the enteric nervous system. GSK3179106 is a RET kinase inhibitor that was administered in double-blind, randomized, placebo-controlled single-dose and repeat-dose studies in healthy subjects to investigate its pharmacokinetics and safety/tolerability. In the single-dose study (n = 16), GSK3179106 was dosed from 10 mg to 800 mg, including a food effect arm.

A phase IIa study of afuresertib, an oral pan-AKT inhibitor, in patients with Langerhans cell histiocytosis.

Background: Langerhans cell histiocytosis (LCH) is a clonal neoplasm characterized by widely varied clinical presentations, including multisystem involvement and systemic inflammatory symptoms. The AKT pathway is relevant to survival and proliferation of dendritic cells, and is also often upregulated in hematopoietic malignancies. A clinical response in an adult patient with LCH participating in the first-in-human trial of afuresertib prompted this prospective trial.