Pharmacokinetics and Pharmacodynamics of KT-474, a Novel Selective Interleukin-1 Receptor-Associated Kinase 4 (IRAK4) Degrader, in Healthy Adults.

ABSTRACT: Interleukin-1 receptor-associated kinase 4 (IRAK4), a key component of the Myddosome complex, mediates signaling through toll-like and interleukin-1 receptors. KT-474, a heterobifunctional IRAK4 degrader, was evaluated in a randomized, double-blind, placebo-controlled Phase 1 trial (NCT04772885) in single (25, 75, 150, 300, 600, 1000, and 1600 mg) and multiple (25, 50, 100, and 200 mg once daily [QD] for 14 days; or 200 mg twice weekly) ascending doses in healthy subjects. The pharmacokinetics of KT-474 and its diastereomers, the pharmacodynamics of KT-474, and the effect of food on KT-474 pharmacokinetics and the pharmacokinetic-pharmacodynamic analysis are presented as additional analyses to supplement the Ackerman et al. publication. KT-474 showed delayed absorption and prolonged elimin

SUBMITTER: Agarwal S 

PROVIDER: S-EPMC11889407 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature