Unknown

Dataset Information

0

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


ABSTRACT: 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.

SUBMITTER: Maldonado MDM 

PROVIDER: S-EPMC6843717 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Maldonado María Del Mar MDM   Rosado-González Gabriela G   Bloom Joseph J   Duconge Jorge J   Ruiz-Calderón Jean F JF   Hernández-O'Farrill Eliud E   Vlaar Cornelis C   Rodríguez-Orengo José F JF   Dharmawardhane Suranganie S  

ACS omega 20191023 19


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 supercri  ...[more]

Similar Datasets

| S-EPMC5418092 | biostudies-literature
| S-EPMC8643341 | biostudies-literature
| S-EPMC10956050 | biostudies-literature
| S-EPMC9685587 | biostudies-literature
| S-EPMC9143669 | biostudies-literature
| S-EPMC4306626 | biostudies-literature
| S-EPMC6992569 | biostudies-literature
| S-EPMC9370278 | biostudies-literature
| S-EPMC6027907 | biostudies-literature
| S-EPMC7549613 | biostudies-literature