Home |
About Us |
Investor Relations |
Products & Services |
Science & Technology |
People |
News & Events |
Contact Us
Cloe®
Predict | Cloe®
Screen
| Cloe®
Select
| Publications
Library | FAQs |
|
 |
|
||
 |
||
| |
|
 |
 |
|
In what format should test compounds be sent to Cyprotex? The best way to send compounds for most of the screening is on a 96-well plate, either heat-sealed with a foil or with a "cap-mat" pressed into place. The cap-mat is a single plastic lid for the plate - it has indentations that seal each well individually. Plates containing 96 individual tubes are not a good idea, because the lids can easily pop off and cause leakage. The product codes for recommended plates and seals are:
What information does Cyprotex require to perform the assays? Accurate MW, indicate whether it is a salt, compound id and optionally molecular formulae How long does it take from order to report? With regular scheduled work, most of our core Cloe® Screen assays return results within 10 working days of the scheduled start date of the study, providing that they are delivered in the right format with the required compound information for the assays in question. There are exceptions to this which include CYP450 induction using fresh human hepatocytes and tailored assays. Are your assays customized for our purpose? If you require specific protocol changes after reviewing our protocols and perhaps performing a trial plate of compounds through the desired assays, then we are happy to discuss making changes to the protocols. However, this would require additional cost over the standard pricing. Do we have any predicted vs real PK data for oral and iv dosing? Yes, lots! The graphs are in the overview presentation, we have a great deal more validation data which we can share under CDA. Overall stats are better for human, we think it reflects on the nature of the compounds. The human data are from late stage clinical trials so compounds are more soluble; rat data comes from earlier projects where solubility issues are abundant (and can lead to inaccuracies in input data as well variations in the corresponding in vivo data). In addition we have to compare predictions to observed data where the rats may have been given formulated compound - leading to some differences not reflective of Cloe® PK accuracy. How many compounds do we use in building the models? Cloe® PK is driven by ADME and physicochemical properties, not structures - so we picked compounds that covered property space for all the input parameters. This was over 200 compounds in each species. The data was used to construct the optimization of partitioning into tissues - the only component which is optimized in Cloe® PK. We have been very careful to concentrate on the modeling of physiology so that Cloe® PK stands up to ANY chemistry - and this is borne out in our most recent comparison of Cloe® PK versus allometric scaling from in vivo studies, soon to be submitted for publication. As soon as I have the manuscripts in their accepted format I'll send them out to interested parties. Do we have data on predictions for poorly soluble & low permeability compounds? A large number of our evaluation compounds from biotech and pharma companies were of this type. You have the rat oral and iv observed vs predicted graphs - and the validation paper. In general we found that as long as solubility was >2 uM, we can predict well. The problem is that below this value, input data is unreliable due to insolubility of the compound in the in vitro assays. Predicting PK values for low permeability compounds has not been seen to be problematic. |
|
|
 |
|
