AB-452(AB-452) - 药物靶点：PAPD5 x PAPD7_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

PAPD5 x PAPD7

作用机制

PAPD5抑制剂(Non canonical RNA polymerase PAPD5 inhibitors)、PAPD7抑制剂(PAPD7-PAP相关结构域7)

治疗领域

感染消化系统疾病

在研适应症-

非在研适应症

乙型肝炎

原研机构

Baruch S. Blumberg Institute

在研机构-

非在研机构

Arbutus Biopharma Corp.

Baruch S. Blumberg InstituteAlumni Association Of Drexel University College Of Medicine

最高研发阶段终止临床前

首次获批日期-

最高研发阶段(中国)-

特殊审评-

结构

分子式C21H26N2O6

InChIKeyUZKFYFNINMJEGT-HNNXBMFYSA-N

CAS号2226178-35-2

关联

1

项与 AB-452 相关的临床试验

ACTRN12618001438246 / Withdrawn临床1期

A Double-Blind, Randomized, Placebo-Controlled, Single and Multiple Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AB-452 Following Oral Administration in Healthy Subjects and Subjects with Chronic Hepatitis B

开始日期2018-10-08

申办/合作机构

Arbutus Biopharma Corp.

100 项与 AB-452 相关的临床结果

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100 项与 AB-452 相关的转化医学

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100 项与 AB-452 相关的专利（医药）

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1

项与 AB-452 相关的文献（医药）

2024-01-25·Journal of Medicinal Chemistry1区 · 医学

Structure–Activity Relationships and Discovery of (S)-6-Isopropyl-2-methoxy-3-(3-methoxypropoxy)-10-oxo-5,10-dihydro-6H-pyrido[1,2-h][1,7]naphthyridine-9-carboxylic Acid (AB-452), a Novel Orally Available HBV RNA Destabilizer

1区 · 医学

Article

作者: Chiu, Tim ; Liu, Fei ; Harasym, Troy ; Tang, Sunny ; Dorsey, Bruce D. ; Lee, Amy C.-H. ; Chen, Shuai ; Gotchev, Dimitar ; Nguyen, Duyan ; Sofia, Michael J. ; Gao, Min ; Kakarla, Ramesh ; Dugan, Benjamin ; Cole, Andrew G. ; Bailey, Laurèn

Approved therapies for hepatitis B virus (HBV) treatment include nucleos(t)ides and interferon alpha (IFN-α) which effectively suppress viral replication, but they rarely lead to cure. Expression of viral proteins, especially surface antigen of the hepatitis B virus (HBsAg) from covalently closed circular DNA (cccDNA) and the integrated genome, is believed to contribute to the persistence of HBV. This work focuses on therapies that target the expression of HBV proteins, in particular HBsAg, which differs from current treatments. Here we describe the identification of AB-452, a dihydroquinolizinone (DHQ) analogue. AB-452 is a potent HBV RNA destabilizer by inhibiting PAPD5/7 proteins in vitro with good in vivo efficacy in a chronic HBV mouse model. AB-452 showed acceptable tolerability in 28-day rat and dog toxicity studies, and a high degree of oral exposure in multiple species. Based on its in vitro and in vivo profiles, AB-452 was identified as a clinical development candidate.

100 项与 AB-452 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
乙型肝炎	临床前	-	Baruch S. Blumberg Institute	-
乙型肝炎	临床前	-	Alumni Association Of Drexel University College Of Medicine	-
乙型肝炎	临床前	美国	Arbutus Biopharma Corp.	-