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

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:23

Article

Byeon, Seong Rim¹  Kim, Hyunjin Vincent¹  Jeon, Mijin¹  Ahn, Young Gil²  Kim, Maeng Sup²  Kong, Jae Yang³  Kim, Hye Yun¹  Kim, Young Soo¹  Kim, Dong Jin¹ 

[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

关键词: Amyloid-beta;    Alzheimer's disease;    Aggregation inhibitor;    Pharmacokinetics;    Behavior test;   

DOI  :  10.1016/j.bmcl.2013.02.104

来源: Elsevier

【 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.

【 授权许可】

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