ADME Transil Assays

XpressBio and Sovicell are dedicated to providing trusted state-of-the-art ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicology) products that enable our customers to rapidly obtain accurate and reproducible pharmacokinetic data about their drug candidates or other test substances.

 

XpressBio and Sovicell ready-to-use kits for ADMET (A: absorption, D: distribution, M: metabolism, E: excretion, T: toxicology) support preclinical research programs in drug discovery. For pharmaceutical R&D, the Company’s products facilitate a shift from labor intensive “home-brew” approaches to fully automated, minimal labor, processes. This in turn provides increased flexibility, reduced cost and increased efficiency of the drug discovery process.

TRANSIL Plasma Protein Binding Assays

Assessing plasma protein binding is important because only the unbound fraction (fu) of a drug can penetrate cell membranes. Thus, only a drug’s unbound fraction is responsible for its pharmacological effect. At the same time, it is only the unbound fraction upon which metabolizing enzymes in the liver and filtration in the kidneys act, thus plasma binding reduces clearance and increases a drug’s half-life.

Many drugs, especially lipophilic compounds, bind to circulating plasma proteins, such as human serum albumin (HSA), α1-acid glycoprotein (AGP), globulins, and lipoproteins. Among these proteins, HSA and AGP are the most important for the reduction of the exposure to xenobiotics because of their ability to bind a large array of structurally unrelated drugs in distinct binding sites.

TRANSIL Membrane Binding & Permeability Assays

Drug transport can broadly be divided into transcellular and paracellular processes. Transcellular movement, which involves the passage of drugs through the cells, is the most common router of drug transport. However, a small fraction of highly polar or very small drugs are able to utilize the paracellular route between the cells.

While a drug’s size, it’s lipophilicity and charge influence its ability to passively diffuse through membranes, diffusion is also influenced by the drug’s structure and in particular its structure-structure interactions with the membrane.

Moreover, increasing a drug’s lipophilicity is not necessarily increasing its propensity to traverse through cell membranes. In fact, the higher a drug’s affinity to the membranes, the more likely it is to enter the membrane and not come out again. That means that drug can get effectively trapped in the membranes – a phenomenon well known as brain tissue binding or microsomal binding. This also has toxicological consequences as the compound accumulates the bodies tissues.

Sovicell’s propritery TRANSIL technology is both patented and trademarked. Its name is derived from transition silica and refers to proprietary surface modified porous silica beads which serve as a carrier material for biological molecules or structures such proteins, enzymes and membranes.

  • Protein binding assays:

–Albumin: HSA, RSA, MSA, BSA

–α1-acid glycoprotein: AGP/AAG

–Approximate plasma: PPB (= HSA + AGP)

 

  • Membrane binding assays =       Membrane affinity assays

-Phosphatidylcholine: Intestinal absorption

-Brain lipid extracts: Brain absorption

-Liver microsomes extracts: Microsomal binding

-Intracellular binding

  • Combined

-High sensitivity binding assay: Membranes + Full plasma

TRANSIL assays are ready-to-use assay kits for
–    Brain tissue binding
– Brain-to-plasma distribution prediction
–    Liver microsomal binding
–    Plasma protein binding
• All TRANSIL Assays are highly defined and reproducible
• Intrinsic quality control
• Matrix free, fast & easy high-throughput assay
– Minimal labor requirements through automation
–  Multiplexing capability
–  Highly cost effective

1. Brain Tissue Binding
2. Brain-to-Plasma Distribution
3. Liver Microsomal Binding
4. Plasma Protein Binding