Investigation of CYP3A induction by PF-05251749 in early clinical development: comparison of linear slope PBPK prediction and biomarker response

Investigation of CYP3A induction by PF-05251749 in early clinical development: comparison of linear slope PBPK prediction and biomarker response
Clin Transl Sci. 2022 Jun 21. doi: 10.1111/cts.13352. Online ahead of print.ABSTRACTPF-05251749 is a dual inhibitor of casein kinase 1 δ/ε under clinical development to treat disruption of circadian rhythm in Alzheimer's and Parkinson's disease. In vitro, PF-05251749 (0.3-100 μM) induced CYP3A in cryopreserved human hepatocytes, demonstrating non-saturable, dose-dependent CYP3A mRNA increases, with induction slopes ranging from 0.036-0.39 μM-1 . ... read more
Source: PubMedPublished on 2022-06-22By Jian Lin