Orca's selective RORγ inhibitors block the differentiation of human Th17 cells without affecting differentiation of Th1 cells.
In collaboration with Dr Fraydoon Rastinejad at the Sanford-Burnham Medical Research Institute (SBMRI) in Lake Nona, Florida, we are now using high-resolution crystal structures of some of our compounds bound to RORγt to optimise our current leads and develop new classes of inhibitor.
Key attributes of the Orca lead compound:
- Highly potent (nanomolar) inhibitor of RORγt activation with selectivity against other related nuclear hormone receptors
- Inhibits differentiation of Th17 cells in vitro and in vivo
- Acceptable in vitro ADME characteristics amenable to further optimization