Orca's selective RORγ inhibitors block the differentiation of human Th17 cells without affecting differentiation of Th1 cells.
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. Our focus on a differentiated allosteric mode of action has yielded potent and selective inhibitors with improved drug-like properties. 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