Adriforant HCl (PF-3893787 HCl) is a new histamine H4 receptor affinity antagonist (Ki=2.4 nM) and a functional H4 receptor blocker (antagonist) (Ki=1.56 nM).

Physicochemical Properties

Molecular Formula	C13H25CLN6O
Molecular Weight	316.830200910568
Exact Mass	370.12
CAS #	2096455-90-0
PubChem CID	131801117
Appearance	White to off-white solid powder
Hydrogen Bond Donor Count	6
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	5
Heavy Atom Count	22
Complexity	295
Defined Atom Stereocenter Count	1
SMILES	N([C@@H]1CCN(C2=NC(N)=NC(NCC3CC3)=C2)C1)C.Cl.O
InChi Key	ZAZAFXLCZSALFI-FYBBWCNBSA-N
InChi Code	InChI=1S/C13H22N6.3ClH/c1-15-10-4-5-19(8-10)12-6-11(17-13(14)18-12)16-7-9-2-3-9;;;/h6,9-10,15H,2-5,7-8H2,1H3,(H3,14,16,17,18);3*1H/t10-;;;/m1.../s1
Chemical Name	4-N-(cyclopropylmethyl)-6-[(3R)-3-(methylamino)pyrrolidin-1-yl]pyrimidine-2,4-diamine;trihydrochloride
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro

Based on functional assay data, convergent predictions of effective free plasma concentrations and rapid on/fast off of rhH4R by Adriforant were observed when the compound was tested and observed for H4R, with binding Ki=2.4 nM and functional Ki=1.56 nM (compound 13). Actin polymerization is measured in vitro using natively isolated human eosinophils, and the IC50 is 1.16 nM. The suggested concentration is 12 nM if it is assumed that 10-fold the IC50 is needed to achieve >90% receptor occupancy (and thus almost complete inhibition of the response). The whole blood GAFS assay data show that at a total blood concentration of 30 nM (corrected for PPB and blood partitioning equivalent to approximately 10 nM free), imetit-induced shape changes are completely blocked. Ceff/Cmin concentrations between 10–15 nM are utilized for safety margin computations and dose prediction [1].

References

[1]. 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.

Solubility Data

Solubility (In Vitro)	H2O : ~100 mg/mL (~269.01 mM) DMSO : ≥ 83.33 mg/mL (~224.16 mM)
Solubility (In Vivo)	Solubility in Formulation 1: 100 mg/mL (269.01 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.1563 mL	15.7813 mL	31.5627 mL
	5 mM	0.6313 mL	3.1563 mL	6.3125 mL
	10 mM	0.3156 mL	1.5781 mL	3.1563 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.