Adriforant (Tartrate)

PF-3893787 Tartrate is a novel histamine H4 receptor antagonist binding affinity (K_i=2.4 nM) and is also a functional (K_i=1.56 nM) antagonist. IC50 & Target: Ki: 2.4 nM (H4R bind), 1.56 nM (H4R func)^[1] In Vitro: PF-3893787 is tested and observed binding K_i=2.4 nM and functional K_i=1.56 nM for H4R. Data from functional assays produce convergent projections of the free plasma efficacious concentration and PF-3893787 (Compound 13) is fast on/fast off on rhH4R. The in vitro IC₅₀ on human native isolated eosinophils assessing actin polymerisation is 1.16 nM and assuming need 10 times the IC₅₀ for >90% receptor occupancy (and therefore near complete inhibition of the response) suggested a concentration of 12 nM. The data in the whole blood GAFS assay demonstrates that the imetit induced shape change is completely blocked at a total blood concentration of 30 nM (which correcting for PPB and blood partitioning equates to approximately 10 nM free). For the purpose of dose projection and safety margin calculation, a Ceff/Cmin concentration of 10-15 nM is used^[1].