SOM230:生长激素抑制素peptidomimetic广泛生长激素释放抑制因子(研)受体结合和独特antisecretory概要文件。

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布鲁斯C,刘易斯我盐水U, Meno-Tetang G, Weckbecker G

SOM230:生长激素抑制素peptidomimetic广泛生长激素释放抑制因子(研)受体结合和独特antisecretory概要文件。

146年5月,欧元J性。2002 (5):707 - 16。

PubMed ID

11980628 (在PubMed

]

文摘

目的:本研究的目的是确定一个小,新陈代谢稳定生长激素释放抑制因子(研)模拟更普遍约束力的概要文件类似于自然生长激素抑制素,从而提高员工的药理性质,因此新治疗使用。设计:一个理性药物设计方法是紧随其后的是合成alanine-substituted SRIF-14类似物来确定单个氨基酸的重要性SRIF-14研受体亚型绑定。结构元素的掺入SRIF-14 cyclohexapeptide稳定形式的模板修改非自然氨基酸导致小说的识别cyclohexapeptide SOM230。结果:SOM230高亲和力结合研受体亚型sst1, sst2, sst3 sst5和显示一个30 - 40倍亲和力sst1和sst5高于Sandostatin (octreotide;短信201 - 995)或Somatuline(女子23014)。体外,SOM230有效抑制生长激素释放激素(GHRH)全身的生长激素(GH)在大鼠垂体细胞的主要文化的集成电路(50)0.4 + / - -0.1 nmol / l (n = 5)。体内,SOM230也强有力地抑制GH分泌的老鼠。艾德(50)值在1 h和6 h后确定注入SOM230表示其体内的行动很长时间。这个属性也反映在药代动力学研究比较等离子体水平的SMS 201 - 995和SOM230皮下后的应用程序。而SMS 201 - 995有一个终端消除半衰期2 h,这是明显延长SOM230-treated动物(t (1/2) = 23 h)。此外,在老鼠SOM230表现出更高的功效降低血浆胰岛素样生长因子(IGF-I)水平与SMS 201 - 995。 The infusion of 10 microg/kg/h of SOM230 using subcutaneously implanted minipumps decreased plasma IGF-I levels far more effectively than SMS 201-995. After 126 days of continuous infusion of SOM230 plasma IGF-I levels were decreased by 75% of placebo-treated control animals. For comparison SMS 201-995, when used under the same experimental conditions, resulted in only a 28% reduction of plasma IGF-I levels, indicating a much higher efficacy for SOM230 in this animal model. It is important to note that the inhibitory effect of SOM230 was relatively selective for GH and IGF-I in that insulin and glucagon secretion was inhibited only at higher doses of SOM230. This lack of potent inhibition of insulin and glucagon release was also reflected in the lack of effect on plasma glucose levels. Even after high dose treatment over 126 days no obvious adverse side effects were noticed, including changes in plasma glucose levels. CONCLUSION: We have identified a novel short synthetic SRIF peptidomimetic, which exhibits high affinity binding to four of the five human SRIF receptor subtypes and has potent, long lasting inhibitory effects on GH and IGF-I release. Therefore SOM230 is a promising development candidate for effective GH and IGF-I inhibition and is currently under evaluation in phase 1 clinical trials.

beplay体育安全吗DrugBank数据引用了这篇文章

药物靶点

药物	目标	类	生物	药理作用	行动
Pasireotide	生长激素抑制素受体1型	蛋白质	人类	未知的	不可用	细节
Pasireotide	生长激素抑制素受体2型	蛋白质	人类	未知的	不可用	细节
Pasireotide	生长激素抑制素受体类型3	蛋白质	人类	未知的	不可用	细节
Pasireotide	生长激素抑制素受体类型5	蛋白质	人类	未知的	不可用	细节