In silico molecular docking model
We exploited this finding to create an in silico tool that could enable us to design and screen New Chemical Entities with an anti-inflammatory Mode of Action and a safety profile similar to 5-ASA.
A large number of structures of PPARγ Ligand Binding Domain (LBD) co-crystallized with a panel of partial and full agonists (RCSB Protein Data Bank) gave the possibility to carry out docking simulations to predict the binding mode of 5-ASA into PPARγ LBD (Farce et al, 2009).
Rational Drug Design of New Chemical Entities
On this basis, a large set of different compounds theoretically able to bind into PPARγ LBD in a 5-ASA similar mode was rationally designed, and docking simulations were carried out to screen the designed molecules based on their putative binding mode.
These NCEs were further screened in silico for chemical accessibility, patentability, ADMET properties; the best scorers synthesized and screened in vitro for their anti-inflammatory effects.