AASLD2018[458F]一种新型HBV衣壳形成抑制剂 添加剂抑制病毒复制

StephenW

458F
A Novel HBV Capsid Formation Inhibitor
That Additively Inhibits Virus Replication in
Combination with Tenofovir or IFN-α
Zhijun Zhang, Bo Liang, Yun-Yueh Lu and Huanming Chen,
Zhimeng Biopharma
Background: Currently approved drugs for chronic hepatitis
B do not provide a cure for the majority of patients. New
classes of direct antivirals that bring additive inhibitory effect
against HBV when used in combination with current drugs are
urgently needed.Methods: Medicinal chemistry and HepG2
cell-based assays were used for synthesizing, testing and
selecting small molecule compounds. Candidate compounds
were tested against HBV infection and HBsAg expression
in PHH assay.Results: We have discovered a novel series
of HBV capsid formation inhibitors (represented by CBHBV-
001) that is structurally distinctive from the current class
I (BAY-41-4109 as the prototype) and class II (represented
by AT-130) HBV capsid protein allosteric modulators. CBHBV-
001 promotes the formation of capsid devoid of HBV
pgRNA and DNA in a dose-dependent manner. CB-HBV-001
inhibits different genotypes of HBV strains and those that
are resistant to current NA HBV inhibitors. In addition, CBHBV-
001 inhibited HBV replication in a dose-dependent
fashion in a hydrodynamic-injection HBV mouse model. More
importantly, in PHH assay, CB-HBV-001 demonstrated an
additive effect with Tenofovir in inhibiting HBV DNA replication,
while it showed an additive effect with IFNa in inhibiting both
HBsAg and DNA. Conclusion: These characters of CBHBV-
001 plus its favorable PK and safety profiles in animal
models warrant its further development in clinical studies.
Disclosures:
Zhijun Zhang – ZhiMeng Biopharma: Employment

StephenW

458F
一种新型HBV衣壳形成抑制剂
添加剂抑制病毒复制
与替诺福韦或IFN-α联合使用
张志军，梁亮，陆云月，陈焕明，
志盟生物制药有限公司
背景：目前批准的慢性肝炎药物
B不能为大多数患者提供治疗方法。新
一类具有附加抑制作用的直接抗病毒药物
当与现有药物联合使用时，对抗HBV
急需。方法：药物化学和HepG2
基于细胞的分析用于合成，测试和
选择小分子化合物。候选化合物
测试了HBV感染和HBsAg表达
在PHH测定中。结果：我们发现了一个新的系列
HBV衣壳形成抑制剂（以CBHBV-代表）
001）在结构上与当前类不同
我（BAY-41-4109作为原型）和II类（代表
通过AT-130）HBV衣壳蛋白变构调节剂。 CBHBV-
001促进了没有HBV的衣壳的形成
pgRNA和DNA呈剂量依赖性。 CB-HBV-001
抑制HBV毒株的不同基因型和那些
对目前的NA HBV抑制剂有抗药性。此外，CBHBV-
001以剂量依赖性抑制HBV复制
流体动力学注射HBV小鼠模型的时尚。更多
重要的是，在PHH测定中，CB-HBV-001表现出一种
替诺福韦抑制HBV DNA复制的加性效应，
而它显示出IFNα抑制两者的累加效应
HBsAg和DNA。结论：CBHBV-的这些特征
001加上其有利的PK和动物安全性
模型保证其在临床研究中的进一步发展。
披露：
Zhijun Zhang - ZhiMeng Biopharma：就业