Toreforant

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

Toreforant (JNJ-38518168) 是一种有效的选择性组胺 H4 受体 (H4R) 拮抗剂，Ki 为 8.4 nM。

Toreforant (JNJ-38518168) is a potent, selective histamine H4 receptor (H4R) antagonist with Ki of 8.4 nM, shows excellent selectivity over other receptors including the other histamine receptors; JNJ-38518168 acts as an antagonist in all species tested and inhibits histamine-induced eosinophil shape change in vitro; demonstrates anti-inflammatory activities in mouse models of asthma and arthritis.Rheumatoid Arthritis Phase 2 Clinical.

In human polymorphonuclear leukocytes, Toreforant inhibits the histamine-induced shape change of human eosinophils and produces a rightward shift in the histamine dose response curves indicating that it is acting as an antagonist of the human H4R in these primary cells. This is not an equilibrium measurement and therefore the calculation of a pA2 is complicated. The pA2 can be estimated using the shift seen the lowest concentration of antagonist. This yields a pA2 of around 7.5 consistent with the results in the transfected system. This assay can also be performed in whole blood and, as for the purified cells, Toreforant is able to inhibit the actions of histamine. The IC50 values are 296 nM and 780 nM when 100 nM and 300 nM histamine are used, respectively.

The animals treated with 100 mg/kg toreforant have reduced disease severity scores. The reduction in scores is similar to JNJ 28307474. A model of histamine-induced scratching in CD-1 mice (n=5 per group) is used to judge the anti-pruritic effects of Toreforant. Unlike other H4R antagonists, Toreforant is not efficacious in reducing histamine-mediated pruritus. After oral administration to rats, Toreforant-derived radioactivity is widely distributed into tissues; however, it is not quantifiable in cerebellum, cerebrum, medulla, and spinal cord in either Long Evans or Sprague Dawley rats, suggesting that drug-derived radioactivity does not cross the blood-brain barrier. Neuropathic pain models in rats are conducted with Toreforant and an H4R antagonist that does cross the blood-brain barrier, JNJ 39758979. In a rat spinal nerve ligation model JNJ 39758979 was able to significantly attenuate the mechanical allodynia induced in the model, however Toreforant has no activity.

JNJ-38518168 | JNJ38518168

GPCR/G Protein

Histamine Receptor

Histamine Receptor

Inflammation/Immunology

Rheumatoid Arthritis

952494-46-1

392.551

C23H32N6

>98% (HPLC)

In Vitro:?DMSO : 100 mg/mL (254.75 mM)

CN1CCC(CCCNC2=NC=C(C3=NC4=C(C)C=C(C)C=C4N3)C(C)=N2)CC1

5-(4,6-dimethyl-1H-benzimidazol-2-yl)-4-methyl-N-[3-(1-methylpiperidin-4-yl)propyl]pyrimidin-2-amine

(-20℃)

With Ice Pack

≥ 2 years