Absorption Screening:
Create the best First Step in ADMETox
|
-
Incorporate automated PAMPA technology from pION at the front end of Caco-2 to streamline
the process:
- FASTER - Results in less than two hours
- BETTER - Simplifies the process and produces quality data (Gastro-intestinal and blood brain barrier passive drug permeability models strongly correlate to cell-based studies)
- COST EFFICIENT - Averages about $2 per data point
The PAMPA Evolution 96 data management and analysis package speeds decision-making for further
drug development.
|
|
PAMPA Sandwich System for Permeability Assay
|
|
|
Parallel Artifical Membrane Permeability Analysis (PAMPA)
|
-
The acceptor wells contain chemical scavengers that
mimic in vivo carrier proteins, and the donor wells have
varying pH that model physiological chemistry.
|
|
|
|
HUMAN JEJUNAL PERMEABILITIES (HJP) VS. pION’S DOUBLE-SINK* PAMPA MODEL
|
-
pION’s Double-Sink method for PAMPA uses a
proprietary phospholipid formulation to create an
artificial membrane that models absorption in the GI
tract by measurement of permeability at multiple pH.
|
|
|
|
BLOOD BRAIN BARRIER VS. DOUBLE-SINK PAMPA
|
-
Measure of drug permeability across the blood brain barrier
(BBB model) is also supported on the workstation by the use of a different phospholipid formulation.
|
|
Absorption Screening: µSOL Technology
|
-
pION’s μSOL technology on the Biomek FX ADMETox Workstation is a high-throughput assay in 96-well
format using a modified "Shake Flask" method. The assay is performed at multiple pH and uses UV
technology to measure both kinetic and thermodynamic solubility. Test compound solutions are mixed using
the appropriate pH buffer, and then filtered using the on-deck filtration system (kinetic) or incubated
(thermodynamic) to enable the differentiation of soluble vs. insoluble drug compounds by UV scan. This
technique has a lower limit of solubility detection at 0.1 mg/mL and an upper limit between 100-200 mg/mL.
|
|
|
|
pION's PAMPA Evolution 96 Software
|
-
pION-developed PAMPA Evolution 96
software controls all liquid handling steps on
the Biomek FX during the assay protocol,
performs the UV scans on the SpectraMAX
(Molecular Devices: Sunnyvale, Calif.) and
handles all data analysis for the PAMPA
and μSOL assays. Assay modifications,
necessitated by particular sets of test drug
compounds, are readily made within the
PAMPA software and automatically translated
to liquid handling steps on the Biomek FX.
The Client Report* feature enables all 96-well
data to be assessed at a single glance, and is
also printable.
|
|
Metabolism and Toxicology Screening
|
-
The Biomek FX ADMETox Workstation also offers automated solutions for in vitro metabolism and
toxicology screening. Template methods are available for the following supported assays:
P450 inhibition studies
- P450-Glo**
- LC-MS/MS-based
Cellular proliferation studies
- CellTiter-Glo**
- CellTiter-Blue**
Apoptosis
- Caspase-Glo** 3/7
- Caspase-Glo** 8
- Caspase-Glo** 9
- Apo-ONE** Homogeneous Caspase-3/7
|
|
