Non-linear IV pharmacokinetics of the ATR inhibitor berzosertib (M6620) in mice.

ABSTRACT:

Background

The Ataxia Telangiectasia and Rad3-related (ATR) protein complex is an apical initiator of DNA damage response pathways. Several ATR inhibitors (ATRi) are in clinical development including berzosertib (formerly M6620, VX-970). Although clinical studies have examined plasma pharmacokinetics (PK) in humans, little is known regarding dose/exposure relationships and tissue distribution. To understand these concepts, we extensively characterized the PK of berzosertib in mouse plasma and tissues.

Methods

A highly sensitive LC-MS/MS method was utilized to quantitate berzosertib in plasma and tissues. Dose proportionality was assessed in female BALB/c mice following single IV doses (2, 6, 20 or 60 mg/kg). A more extensive PK study was conducted in tumor-bearing mice follo

SUBMITTER: Deppas JJ 

PROVIDER: S-EPMC11390321 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature