H4R antagonist 1

• CAT Number: I019633
• CAS Number: 1429375-54-1
• Molecular Formula: C11H11BrN8
• Molecular Weight: 335.16
• Purity: ≥95%
• Synonyms: 1-(12-bromo-2,3,4,5,8,10-hexazatricyclo[7.4.0.02,6]trideca-1(9),3,5,7,10,12-hexaen-7-yl)-N-methylazetidin-3-amine
• InChI: InChI=1S/C11H11BrN8/c1-13-7-4-19(5-7)10-11-16-17-18-20(11)8-2-6(12)3-14-9(8)15-10/h2-3,7,13H,4-5H2,1H3
• InChIKey: ICGICUHMULRYIQ-UHFFFAOYSA-N
• SMILES: CNC1CN(C1)C2=NC3=C(C=C(C=N3)Br)N4C2=NN=N4

H4R antagonist 1 is a potent and highly selective histamine H4 receptor (H4R) antagonist with an IC50 of 27 nM. H4R antagonist 1 does not show any noticeable binding affinity to other subtypes of histamine receptors, H1R, H2R, and H3R[1].
The competitive binding assay against a wider panel of GPCR, ion channel, and transporters at the concentration of 10 μM reveals that H4R antagonist 1 (Compound 48) is highly selective for H4R. The inhibitory activity of H4R antagonist 1 against mouse H4R (IC50=0.29 μM) is about 10 times weaker than that for human H4R[1].
H4R antagonist 1 (Compound 48) shows significant antipruritic and anti-inflammatory efficacy in Oxazolone-induced murine model mimicking human atopic dermatitis (AD)[1].
In the [35S]GTPγS functional assay, H4R antagonist 1 shows inhibitory activity against mouse H4R with an IC50 of 0.69 μM[1].

Reference

[1]. Ko K, et al. Discovery of a Novel Highly Selective Histamine H4 Receptor Antagonist for the Treatment of Atopic Dermatitis. J Med Chem. 2018 Apr 12;61(7):2949-2961.
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