Quantification

Subcellular drug quantification services

By using our proprietary technologies, we are the only provider to determine subcellular drug concentrations

Currently, pharmacokinetic profiling uses drug concentrations up to organ or total cellular levels. This does unfortunately not provide information about the actual drug concentration at the molecular target, which is expected to contribute to incorrect prediction of a drugs efficacy and safety. Subcellular concentrations are even more important for novel drug classes, which have a poor membrane permeability, but also for therapies that depend on advanced delivery systems. The notion that approximately 50 percent of all drug targets are located in organelles further emphasizes the importance of subcellular drug distribution. Cell-specific structural differences contribute to organ-specific differences in drug concentrations and a poor inter species predictability of pharmacokinetic behavior. This emphasizes the importance of a compound’s subcellular distribution which we can provide.

Our subcellular quantification services will be provided as in-house service or can be license-based. Briefly, the following options and decisions can be part of a personalized project plan, to obtain your research goals.

1. Select your subcellular compartment

Our proprietary technology can quantify your compound concentration in eighteen different cellular compartments, including free cytosolic concentrations, a plasma membrane bound fraction, and free and bound concentrations of all organelles (i.e., mitochondria, peroxisomes, lysosomes, Golgi apparatus, endoplasmic reticulum, early endosomes, late endosomes, nucleus).

2. Define uptake kinetics for your project

To determine kinetics of your compound’s cellular uptake and subcellular distribution, we can measure cellular compartmental concentrations at each desired time point. However, a steady-state time point can also be chosen for a more explorative study using multiple concentrations or compounds.

3. Determine the relevant compound concentration

Various concentrations of your compound or advanced drug delivery platform can be evaluated.

4. Pick your preferred report format

After an average lead time of six weeks we will provide you with a subcellular distribution profile. This report can be a short summary of the observations in our test system, but can also include more comprehensive additions like a literature-based extrapolation to other cell types.

1 - PROJECT PLAN

Project plan discussed with and accepted by client

2 - COMPOUND SEND

Client sends compound to QTM

3 - CELL EXPOSURE

Cells are exposed to the compound of interest

4 - FRACTION COLLECTION

Collection of free and bound subcellular fractions

5 - FRACTIONS ANALYSED

Subcellular fractions are analyzed using client-preferred method

6 - SUBCELLULAR DISTRIBUTION PROFILE

The compound distribution profile is reported to client

BENEFITSProviding insights into a compound's subcellular distribution

Pharmacokinetics 2.0

Add a new data layer to your data en get more refined pharmacokinetic profiles with a better predictability.

Increased IVIVE translation

Improve your in vitro to in vivo extrapolation (IVIVE) by better insights in species differences at the subcellular level.

Early stage derisking

Know the exact localization of your compound in an early development phase to save time, money and prevent unnecessary studies.

Enhanced efficiency

Empower your drug’s efficiency by improved subcellular targeting.