Drug metabolism/pharmacokinetic & toxicological properties of remaining potential drugs examined - DMPK & toxcitiy ipS assays
~3 drugs remain in 'lead series'
1. Liver activity assays
  - Liver microsome/hepatocyte survival after drug exposure recorded - drug conc. & effects also noted
  - Lots of SAR info collected
  - Activity CYP450 enzymes assayed to predict drug interactions (allow us predict how drug will interact with P450 enzymes - multiple drug interactions!!)
2. Intestinal absorption assays
  - Drug permeability through Caco-2 cells (Intestinal epithelial cells)
  - Drug applied apical side cell - conc. measured on basolateral side
  - Determines absorption & bioavailability
3. BBB absorption assays
  - in-vitro assays using brain endothelial cells
  - Drug applied blood-facing side of cells - measured on brain side
Compound profiling = Drug properties (pharmacoK, toxicity, metab) discovered in target validation & lead finding phase are compiled & catalogued - Other researchers can know properties of specific compounds without needing to re-use assays

	Erstellt von Niamh McLoughlin vor fast 9 Jahre

Pharmacology (Clinical development ) Notiz am Pre-clinical development , erstellt von Niamh McLoughlin am 05/11/2017.