Drug-Drug Interaction Liabilities with BTK Inhibitor TL-895.

ABSTRACT: TL-895 is an orally administered protein kinase inhibitor in clinical development for the treatment of B-cell malignancies and various other blood and autoimmune disorders. In the early stages of drug development, limited data are available to assess off-target engagement and drug-drug interaction (DDI) liabilities, which may have profound effects on drug safety and efficacy. In this context, we characterized the kinase interaction profile of TL-895 and determined that the agent inhibits Bruton's tyrosine kinase (BTK) and bone marrow kinase on chromosome X (BMX), with more potent inhibition of BMX than BTK in a kinase assay (IC50: 0.53 vs. 3.02 nmol/L) and a bioluminescence resonance energy transfer (BRET) assay (IC50: 1.6 vs. 6.8 nmol/L). We used in vitro and in vivo models to assess DDI

SUBMITTER: Stromatt JC 

PROVIDER: S-EPMC12426595 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature