QUANTIFICATION OF IN VIVO TARGET ENGAGEMENT

Using Microfluidic Activity-Based Protein Profiling

A recent study published in SLAS Technologies by Reardon, H. T., et al., used activity-based protein profiling (ABPP) to accurately measure drug–target interactions in vivo.

The authors needed to accelerate the ABPP workflows and avoid imaging artifacts which make conventional gels challenging to quantify. They utilized the LabChip® GXII Touch microfluidic instrument to assist with this task. The LabChip® GXII Touch protein characterization system provides electrophoretic separation of probe-labeled proteins in tissue lysates and plasma, and quantification of fluorescence to meet these goals.

Automation of the ABPP assay on the LabChip® GXII Touch protein characterization system:

• Delivered an overall time savings of 3–5 h per 96-well sample plate
• Reduced sample consumption significantly facilitating assay miniaturization for scarce biological samples
• Enabled routine assessments of tissue distribution and engagement of targets and off-targets in vivo

Reardon, H. T., at al. incorporated microfluidic ABPP assays into routine in vitro screening and in vivo assessments of target engagement, tissue distribution, and selectivity against off-target enzymes. This enabled direct visualization and comparison of enzyme activity for inhibitors dosed in vivo compared with in vitro treatments and provided a translational advantage and a streamlined, scalable workflow for preclinical drug discovery and development.

Read the Research:

Reardon, H. T., Herbst, R. A., Henry, C. L., Herbst, D. M., Ngo, N., Cisar, J. S., . . . O’Neill, G. P. (2019). Quantification of In Vivo Target Engagement Using Microfluidic Activity-Based Protein Profiling. SLAS TECHNOLOGY: Translating Life Sciences Innovation,247263031985230. doi:10.1177/2472630319852303.

For research use only. Not for use in diagnostic procedures.

2019-11-05T21:21:30+00:00