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更新于：2025-05-07

LY-389382

更新于：2025-05-07

概要

概要

基本信息

药物类型

小分子化药

别名

靶点-

作用方式-

作用机制-

治疗领域

内分泌与代谢疾病

在研适应症-

非在研适应症

2型糖尿病

原研机构

Eli Lilly & Co.

在研机构-

非在研机构

Lilly Research Laboratories

权益机构-

最高研发阶段无进展药物发现

首次获批日期-

最高研发阶段(中国)-

特殊审评-

结构/序列

分子式C22H22Cl2N2O2

InChIKeyNSVUIPZLBUDXLC-UHFFFAOYSA-N

CAS号227799-37-3

关联

100 项与 LY-389382 相关的临床结果

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100 项与 LY-389382 相关的转化医学

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100 项与 LY-389382 相关的专利（医药）

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项与 LY-389382 相关的文献（医药）

2002-09-01·European Journal of Pharmacology3区 · 医学

Inhibition of recombinant KATP channels by the antidiabetic agents midaglizole, LY397364 and LY389382

3区 · 医学

Article

作者: Trapp, Stefan ; Treinies, Iris ; Proks, Peter ; Mest, Hans-Jurgen

Most imidazolines inhibit ATP-sensitive K(+) (K(ATP)) channels. Since these drugs are potentially clinically relevant insulin secretagogues, it is important to know whether extrapancreatic K(ATP) channels are targeted. We examined the effects of three imidazoline-derived antidiabetic drugs on the cloned K(ATP) channel, expressed in Xenopus laevis oocytes, and their specificity for interaction with the pore-forming Kir6.2 or the sulphonylurea receptor (SUR) 1 subunit. Midaglizole, LY397364 and LY389382 blocked Kir6.2deltaC currents with IC(50) of 3.8, 6.1 and 0.7 microM, respectively. The block of Kir6.2/SUR1 currents by LY397364 and LY389382 was best fit by a two-site model, suggesting that these drugs also interact with SUR1. However, since all three drugs interact with the Kir6.2 subunit, and Kir6.2 forms the pore of extrapancreatic K(ATP) channels, these drugs are unlikely to be specific for the beta-cell.

2001-07-01·Naunyn-Schmiedeberg's Archives of Pharmacology4区 · 医学

Glucose-induced insulin secretion is potentiated by a new imidazoline compound

4区 · 医学

Article

作者: Veikko Koivisto ; Jürgen Schloos ; Iris Treinies ; Hans-Jürgen Mest ; Ulrich Giese ; Achim Raap ; Michael Paal

Sulfonylureas stimulate insulin secretion independent of the blood glucose concentration. This can lead to hypoglycaemia in type 2 diabetic patients. Over the last years a number of imidazoline derivatives have been identified that stimulate insulin secretion in a more glucose-dependent way. In agreement with this, our aim was to generate imidazoline derivatives with a potential for the treatment of type 2 diabetic patients. We developed the compound 2-[4-(4-chlorophenyl)-3-(2-methoxyethoxy)-2-naphthalenyl]-4,5-dihydro-1-H-imidazole monohydrochloride (LY389382) with an imidazoline moiety and investigated its effects on glucose-dependent insulin secretion in a beta-cell line, isolated rat islets and in vivo. We could demonstrate that LY389382 induces insulin secretion in MIN6 cells and rat islets in a glucose-dependent manner (EC50=1.1 microM and 0.3 microM, respectively). Furthermore during hyperglycaemia LY389382 increased insulin secretion in a dose-dependent manner in healthy rats, whereas the compound had no effect at euglycemia in a tenfold higher dosage. After 7 days of treatment of Zucker Diabetic Fatty [ZDF/ (Gmi/fa)] rats with LY389382 with a dose of 15 mg/kg twice daily the blood glucose concentration was reduced from 22.7 +/- 1.7 mM to 16.6 +/- 2.3 mM. During the same time period the glucose concentration increased from 21.7+/-1.7 mM to 28.9 +/- 1.3 mM in the vehicle-treated group (P<0.05). The drop of the insulin level was also inhibited by LY389382 in ZDF rats. In contrast to other well-characterised imidazolines that have been shown to induce a glucose-dependent insulin secretion only within a limited range of concentrations, LY389382 stimulates insulin secretion over a concentration range of at least two log units in a glucose-dependent manner. These data suggest that this imidazoline compound has a potential for the treatment of type 2 diabetes.

Gaodeng Xuexiao Huaxue Xuebao

Docking studies on the interaction of imidazolines and potassium ion channel-Kir6.2

作者: Zhang, Rui ; Liu, Yong-Jun ; Wang, Zhi-Guo ; Ling, Bao-Ping ; Liu, Cheng-Bu ; Zhang, Chang-Qiao ; Meng, Xiang-Hua

Kir6.2, a key component of the ATP-sensitive potassium channel (KT_ATP), can directly interact with imidazolines, a kind of potential antidiabetic drug.This paper explored the interaction of Kir6.2 with imidazoline mols. by applying AutoDock software.The docking results reveal the binding sites of the seven imidazolines on Kir6.2.For Efaroxan, Clonidine, Cibenzoline and Bl11282, polar residues, H175, K67 and W68, constitute the binding pocket; while Rx871024, Alinidine and Ly389382, lies in a hydrophobic pocket which is composed of nonpolar residues, F168, M169 and 1296.Efaroxan, Clonidine, Cibenzoline and Bl11282 interact with Kir6.2 mainly by forming hydrogen bonds, but for Rx871024, Alinidine and Ly389382, the hydrophobic interaction is the most important mode of action.These binding sites and the interaction modes can interpret the inhibition of these imidazoline drugs to some extent, and this research may provide theor. support in the pharmacol. study of imidazolines regulating the secretion of insulin.

100 项与 LY-389382 相关的药物交易

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