Pharmacokinetics of the Rac/Cdc42 Inhibitor MBQ-167 in Mice by Supercritical Fluid Chromatography–Tandem Mass Spectrometry

This is the authors' abstract. We don't add key points for this paper.

The Rho GTPases Rac and Cdc42 are potential targets against metastatic diseases. We characterized the small molecule MBQ-167 as an effective dual Rac/Cdc42 inhibitor that reduces HER2-type tumor growth and metastasis in mice by ∼90%. This study reports the pharmacokinetics and tissue distribution of MBQ-167 following intraperitoneal and oral single-dose administrations. We first developed and validated a bioanalytical method for the quantitation of MBQ-167 in mouse plasma and tissues by supercritical fluid chromatography coupled with electrospray ionization tandem mass spectrometry. MBQ-167 was rapidly distributed into the kidneys after intraperitoneal dosing, whereas oral administration resulted in higher distribution to lungs. The elimination half-lives were 2.17 and 2.6 h for the intraperitoneal and oral dosing, respectively. The relative bioavailability of MBQ-167 after oral administration was 35%. This investigation presents the first analysis of the pharmacokinetics of MBQ-167 and supports further preclinical evaluation of this drug as a potential anticancer therapeutic.