By involving ADME / DMPK early in the drug discovery process you can ensure the best molecule is progressed. At Charnwood Discovery, not only do we have a range of in vitro ADME assays available, but we also have experts in different DMPK areas allowing us to offer a tailored approach to your project needs.
In Vitro ADME Assays that Ensure the Right Question is Answered
Our team collaborates with you to customize in vitro ADME assays that effectively address your specific project questions, as a standard practice.
Developing new candidates that combine biological activity with appropriate physicochemical properties is one of the key challenges in the drug discovery process. Therefore, investigating the physical properties alongside the chemical properties of the drug substances is crucial in early drug discovery.
Considering the drug’s permeability is a crucial aspect of the drug discovery process, particularly when aiming for oral delivery. The drug’s ability to cross the cell membrane depends on transporter proteins and membrane permeability.
At Charnwood Discovery, we can measure permeability using the following assays:
PAMPA (Parallel Artificial Membrane Permeability Assay)
PAMPA is measured using Pion Inc’s kit technology, which consists of a membrane coated with lipid to mimic gastrointestinal conditions, allowing the evaluation of the passive permeability of a compound at a range of physiologically relevant pH values.
Caco-2 (Human Colon Epithelial Adenocarcinoma Cells)
21-day differentiated cells are used as model for the human intestinal barrier as they differentiate and polarize to form tight junction and express transporter proteins (e.g., P-glycoprotein and BCRP). This allows for the assessment of both passive and active transport across the monolayer, and enables the determination of an efflux ratio of the test compound.
Contact us to find out more here.
Understanding the metabolism in drug discovery is essential. It influences how much compound is removed before it can exert a therapeutic effect, how long a drug will remain in the body, and the dosing strategy.
The primary organ responsible for the metabolism of drugs is the liver. The liver intrinsic clearance (CLint) is the measurement of the liver’s innate ability to transform and eliminate a drug from the body. This excludes factors such as hepatic blood-flow and protein binding.
Charnwood Discovery also offers metabolite identification. This can be from metabolic stability samples, enabling early identification of the most abundant metabolites. Alternatively, it can come from in vitro or in vivo samples later in the discovery process, allowing for a comprehensive determination of the metabolic profile.
Liver Phase 1 metabolism is studied with the use of liver microsomes, a sub-cellular fraction, that are a useful tool for the in vitro assessment of intrinsic clearance.
Other microsomal fractions can also be studied as required (intestinal or renal).
Find out more here.
Cryopreserved hepatocytes incubated in suspension contain both phase I (cytochrome P450s) and phase II metabolizing enzymes, as well as the necessary co-factors, enabling them to be used at Charnwood Discovery to study liver drug metabolism.
Find more information about our hepatocyte stability assay here.
Additional Services & Capabilities
In addition to in vitro ADME assays, Charnwood Discovery also offers the following services to support clients in identifying the best drug candidates and advancing their projects.
Our core capabilities, in addition to ADME / DMPK services, are
All Under One Roof!
Our compelling ‘under-one-roof’ service ensures that the best scientific minds can quickly and easily collaborate to move your project forward. We recruit from a global talent pool for diversity of intellectual input and, by investing in our scientists’ on-going development, they stay at the cutting edge of the latest advances.