Therapeutic and pharmacokinetic characterizations of an anti-amyloidogenic bis-styrylbenzene derivative for Alzheimer's disease treatment

被引：4

作者：

Byeon, Seong Rim ^{[1
]}

Kim, Hyunjin Vincent ^{[1
]}

Jeon, Mijin ^{[1
]}

Ahn, Young Gil ^{[2
]}

Kim, Maeng Sup ^{[2
]}

Kong, Jae Yang ^{[3
]}

Kim, Hye Yun ^{[1
]}

Kim, Young Soo ^{[1
]}

Kim, Dong Jin ^{[1
]}

机构：

[1] Korea Inst Sci & Technol, Brain Sci Inst, Ctr Neuromed, Seoul 136791, South Korea

[2] Hanmi Pharmaceut Co Ltd, Hanmi Res Ctr, Hwaseong Si, Gyonggi Do, South Korea

[3] Keimyung Univ, Coll Pharm, Dalseo Gu 704701, Daegu, South Korea

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2013年 / 23卷 / 11期

关键词：

Amyloid-beta; Alzheimer's disease; Aggregation inhibitor; Pharmacokinetics; Behavior test; SOLID-PHASE SYNTHESIS; CURCUMIN; DRUG; HYPOTHESIS; PATHOLOGY; PEPTIDE;

D O I：

10.1016/j.bmcl.2013.02.104

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Alzheimer's disease drug discovery regarding exploration into the molecules and processes has focused on the intrinsic causes of the brain disorder correlated with the accumulation of amyloid-beta. An anti-amyloidogenic bis-styrylbenzene derivative, KMS80013, showed excellent oral bioavailability (F = 46.2%), facilitated brain penetration (26%, iv) in mouse and target specific in vivo efficacy in acute AD mouse model attenuating the cognitive deficiency in Y-maze test. Acute toxicity (LD50 > 2000 mg/kg) and hERG channel inhibition (14% at 10 mu M) results indicated safety of KMS80013. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：3467 / 3469

页数：3

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