3 ways Silensomes^TM HLM make reaction phenotyping easier and more relevant

“Simplicity is the soul of efficiency.” 

-Austin Freeman

Looking for ways to simplify your CYP Phenotyping studies? Silensomes^TM Human Liver Microsomes (HLM) may be the answer. Silensomes^TM are validated human pooled liver microsomes chemically and irreversibly inactivated for one specific CYP using mechanism based inhibitors (MBI). 

Each Silensomes^TM HLM is available as cryopreserved, ready-to-use HLMs chemically knocked-out for one specific CYP activity (1A2, 2A6, 2B6, 2C8, 2C9, 2D6, 3A4) showing high specificity and efficiency of their targeted CYP inhibition ( most are >80%), and only minor impact (<20%) on other enzymes. The thaw and go format of Silensomes^TM HLM enables researchers to focus more on results and less on validating the level of CYP inhibitions.

1. You don’t need to have high quality inhibitors on hand.  Silensomes are preinhibited with mechnism based irreversible inhibitors.  This feature alleviates problems researchers have with inhibitor access and quality.  Because Silensomes are preinhibited and prequalified for the level of inhibition, you don’t need to worry whether the inhibitors will work each time you run an experiment.

 

2. Your additive fraction metabolized (fM) calculations will never exceed 100%..  A fundamental problem with the use of recombinant proteins for determining the fraction metabolized by any one enzyme is the addition of all the individual reactions together often exceeds 100%.  This is typically corrected using a relative activity factor (RAF) applied to each enzyme activity which requires seperate reactions to accurately predict.  With Silensomes, the native enzymes are all present in the reaction at their physiological levels with only a single enzyme inactivated.  This eliminates the need for determing and RAF and leads to more accurate prediction of fM.

 

3. Use of FDA-designated inhibitors.  The mechanism based inhibitors used to produce Silensomes are non-proprietary and among those designated in FDA guidance documents.   Not only will you be saving time by alleviating the need to have inhibitors, improving accuracy by eliminating RAF in your calculations, but all the inhibitors used in Silensomes are common and recommended by the FDA in guidance documents.  This feature enables you to use Silensomes data to move candidates through the development pipeline without having to backtrack using another method.