A Pharmacokinetic and Metabolism Study of the TRPC6 Inhibitor SH045 in Mice by LC-MS/MS.

ABSTRACT: TRPC6, the sixth member of the family of canonical transient receptor potential (TRP) channels, contributes to a variety of physiological processes and human pathologies. This study extends the knowledge on the newly developed TRPC6 blocker SH045 with respect to its main target organs beyond the description of plasma kinetics. According to the plasma concentration-time course in mice, SH045 is measurable up to 24 h after administration of 20 mg/kg BW (i.v.) and up to 6 h orally. The short plasma half-life and rather low oral bioavailability are contrasted by its reported high potency. Dosage limits were not worked out, but absence of safety concerns for 20 mg/kg BW supports further dose exploration. The disposition of SH045 is described. In particular, a high extravascular distribution, mo

SUBMITTER: Chai XN 

PROVIDER: S-EPMC8998618 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature