Adriforant  (Synonyms: PF-3893787)

PF-3893787 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.

Ki: 2.4 nM (H4R bind), 1.56 nM (H4R func)^[1]

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].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

262.35

C₁₃H₂₂N₆

943057-12-3

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Mowbray CE, et al. Challenges of drug discovery in novel target space. The discovery and evaluation of PF-3893787: a novel histamine H4 receptor antagonist. Bioorg Med Chem Lett. 2011 Nov 1;21(21):6596-602.  [Content Brief]