RS-1748，一种新型的 CXC 趋化因子受体 4 拮抗剂，可抑制卵清蛋白诱导的豚鼠气道炎症。
RS-1748, a novel CC chemokine receptor 4 antagonist, inhibits ovalbumin-induced airway inflammation in guinea pigs.
机构信息
Biological Research Laboratories, Daiichi Sankyo Co., Ltd., Tokyo, Japan.
出版信息
Biol Pharm Bull. 2010;33(6):1067-9. doi: 10.1248/bpb.33.1067.
CC chemokine receptor 4 (CCR4) is generally recognized as a preferential marker for T helper 2 cells, and we have previously reported morpholine-derivative CCR4 antagonists, RS-1154 and RS-1269. Here, we investigate the pharmacological profiles of a novel pyrimidine-derivative CCR4 antagonist, 2-{4-[2-(diethylamino)ethoxy]phenyl}-N-(2,4-difluorobenzyl)-5-fluoropyrimidin-4-amine (RS-1748), which showed potency to inhibit the bindings of [(125)I]CCL17 and [(35)S]GTPgammaS to human CCR4-expressing Chinese hamster ovary (CHO) cells with IC(50) values of 59.9 nM and 18.4 nM, respectively. Furthermore, RS-1748 inhibited ovalbumin-induced airway inflammation in guinea pigs at a dose of 10 mg/kg. These results indicate that RS-1748 would be a promising lead compound for developing a therapeutic agent against asthma.
CC 趋化因子受体 4（CCR4）通常被认为是 T 辅助 2 细胞的首选标志物，我们之前曾报道过吗啉衍生物 CCR4 拮抗剂 RS-1154 和 RS-1269。在这里，我们研究了一种新型嘧啶衍生物 CCR4 拮抗剂 2-{4-[2-(二乙氨基)乙氧基]苯基}-N-(2,4-二氟苄基)-5-氟嘧啶-4-胺（RS-1748）的药理学特性，该拮抗剂对 [(125)I]CCL17 和 [(35)S]GTPγS 与人 CCR4 表达的中国仓鼠卵巢（CHO）细胞的结合具有抑制作用，IC50 值分别为 59.9 nM 和 18.4 nM。此外，RS-1748 以 10 mg/kg 的剂量抑制了豚鼠卵清蛋白诱导的气道炎症。这些结果表明，RS-1748 将成为开发治疗哮喘药物的有前途的先导化合物。
Zotero 插件