Friday, 17 July 2015

Silensomes: One single model for DMPK phenotyping studies

Silensomes™ are human pooled liver microsomes in which one specific CYP has been chemically knocked out and are capable of directly quantifying and predicting the contribution of CYP enzymes in drug metabolism.

Until now, a battery of in-vitro tests recommended by the regulatory agencies (EMA/FDA) are required for this CYP phenotyping assay. These tests (correlation analysis, antibody or chemical inhibition and metabolism by recombinant human enzymes) have a number of disadvantages:

- No direct quantitative measurement of the contribution of each CYP in the metabolism of a drug (correlation analysis)
- Model is not fully representative of the liver enzyme profile (e.g. human recombinant CYP450)
- Lack of specificity (e.g. anti-CYP antibodies and chemical inhibitors)

To overcome the disadvantages of the current methodologies, Biopredic International has developed a patented new in-vitro drug development model.

Silensomes™ are validated human pooled liver microsomes (HLMs) chemically and irreversibly inactivated for one specific CYP using mechanism based inhibitors (MBI).

Each Silensomes™ is available as ready-to-use HLMs chemically knocked-out for one specific CYP activity (1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4) with each showing high specificity and efficiency of their targeted CYP inhibition (>80%), and only minor impact (<20%),

Key Advantages of Silensomes™:
- Silensomes™: the model of choice for determination of the CYP contribution all along the development plan of a new chemical entity

- Irreversibly inhibited CYPs

- For initial rate conditions

- For saturating conditions

- One single model for CYP phenotyping assays, instead of a battery of in-vitro tests

- Quantitative: the true contribution of the CYP450 in the metabolism of the coumpound can be measured

- A powerful model with an excellent specificity, potency, stability and predictability to ensure reliable extrapolation of the drug-drug interaction risk

- More representative of in-vivo, using human liver microsomes rather than recombinant enzymes isolated from non-mammalian cells

Silensomes™ are available for compound screening purposes and also for regulatory validation

Silensomes are now available for beta testing. Please contact us if you would be interested in this.

Caltag Medsystems are the exclusive UK distributor of Biopredic products. Please call the office on +44 (0)1280 827460 for further information about their products, or email office@caltagmedsystems.co.uk.

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