Plasma Protein Binding, Biostability, Metabolite Profiling, and CYP450 Phenotype of TPB15 Across Different Species: A Novel Smoothened Inhibitor for TNBC Therapy.

ABSTRACT: Background/Objectives: Triple-negative breast cancer (TNBC) is a major cause of cancer-related deaths among women. The Hedgehog (Hh) signaling pathway plays a critical role in tumor development, and targeting this pathway may provide new therapeutic opportunities for TNBC. TPB15 is a novel smoothened inhibitor of the Hh pathway, showing promising tumor reduction and low-toxicity properties in vivo/vitro. This study aims to evaluate TPB15's protein binding rates, metabolic stability, and metabolism across different species, including mice, rats, dogs, monkeys, and humans. Methods: TPB15 was synthesized, and its pharmacokinetic profile was assessed. Plasma protein binding was determined using ultrafiltration across multiple species. Stability studies were conducted in plasma an

SUBMITTER: Wen D 

PROVIDER: S-EPMC12030497 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature