Chemokine receptors are a group of membrane proteins, belong to the seven-transmembrane, G protein-coupled protein superfamily. Chemokines and chemokine receptors regulate tissue-specific migration, maintenance and functions of immune cells. The CC chemokine receptors consist of ten members (CCR1-10). Among them, CCR10 is the last member of the CC chemokine receptor subfamily, and its main ligand chemokines are CCL27 and CCL28. For instance, CCR10 plays an important role in the migration of skin-homing memory T-cells to the skin through activation by CCL27/CTACK or to mucosal epithelia through activation of CCL28. Notably, both CCR10 and CCL27 are associated with inflammatory skin diseases such as allergic contact dermatitis and psoriasis. However, the effect of directly blocking CCR10 on inflammation in the skin is unclear.
BI-6901 is a potent and selective CCR10 antagonist. Compared with other GPCRs (including a number of other chemokine receptors), BI-6901 shows highly selective for CCR10. BI-6901 affects CCR10’s coupling with G-protein as detected in a GTP-binding assay. In addition, this compound also inhibits CCL27 dependent cAMP production in CCR10 transfected HEK cells. Similarly, the enantiomers of BI-6901 show stereospecificity for CCR10 antagonism. Finally, BI-6901 is investigated for efficacy against DNFB (2,4-dinitrofluorobenzene) murine contact hypersensitivity. The result shows that BI-6901 exhibits a dose-dependent anti-inflammatory response to ear swelling in sensitized mice stimulated by DNFB. The efficacy of this compound provides further evidence for the role of CCR10 in dermatological inflammatory conditions.
To sum up, BI-6901 is a selective CCR10 antagonist, which helps to study the role of CCR10 in inflammation and cancer.