Development of novel isoflavone drugs as broad spectrum antivirals

开发新型异黄酮药物作为广谱抗病毒药物

• 批准号: 9302296
• 负责人: Kristin M Bedard
• 金额: $ 74.63万
• 依托单位: KINETA, INC.
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-22 至 2018-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9302296
• 关键词: ADME Study; Animal Model; Antiviral Agents; Antiviral Response; Antiviral Therapy; Back; Biochemical; Biological Assay; Biological Availability; Body Weight decreased; Cells; Characteristics; Chemicals; Clinical; Coronaviridae; Coronavirus; DNA Viruses; Data; Dengue Virus; Development; Dose; Drug Kinetics; Drug or chemical Tissue Distribution; Drug resistance; Ebola virus; Evaluation; Exhibits; Flavivirus; Frequencies; Genetic; Goals; Immune response; In Vitro; Infection; Influenza; Innate Immune Response; Isoflavones; Lead; Mediating; Metabolic; Modification; Mus; Natural Immunity; Nature; Oral; Organ; Pathogenesis; Permeability; Pharmaceutical Chemistry; Pharmaceutical Preparations; Pharmacology; Pharmacotherapy; Phenotype; Pre-Clinical Model; Property; RNA Viruses; Resistance; Safety; Scientist; Solubility; Specificity; Therapeutic; Therapeutic Index; Therapeutic Intervention; Toxicology; Universities; Viral; Viral Respiratory Tract Infection; Virus; Virus Diseases; Virus Replication; Washington; West Nile virus; Work; aqueous; base; drug candidate; drug development; drug discovery; drug mechanism; efficacy study; efficacy testing; fighting; in vivo; influenzavirus; innovation; lead series; lipophilicity; meetings; mouse model; novel; pathogen; pre-clinical; preclinical development; product development; public health relevance; resistant strain; respiratory infection virus; respiratory virus; scaffold; small molecule; viral resistance; virology

 DESCRIPTION (provided by applicant): Kineta has discovered a novel class of broad spectrum small molecule antivirals that function through a host directed mechanism. These compounds have demonstrated an innovative mechanism of action and target several high priority pathogens that are commercially valuable. The lead chromenone-based candidates have potency in the nM range, inhibit multiple viruses including influenza, coronavirus, West Nile, ebola, and dengue virus in vitro and in animal models, have an attractive pharmacologic profile, and are well tolerated in vivo. In this application, we will perform lead optimization and preclinical development of the lead series. The major milestone of the project is to select one or more nominated drug candidates for formal IND-enabling development towards an oral therapeutic for broad respiratory viral infections. Drug treatment to stimulate the host innate immune response is increasingly appreciated as a strategy for therapeutic intervention and has the potential to redefine the paradigm of antiviral drug development. The need for effective antivirals is great, and our approach to stimulate innate immunity in the presence of diverse viral countermeasures has yielded promising leads that are effective against a broad range of RNA and DNA viruses. We have assembled a highly qualified development team that includes the Kineta scientists responsible for the antiviral discovery work and Prof Michael Gale, Jr. of the University of Washington, an expert in innate immunity and the antiviral response.

 描述（由申请人提供）：Kineta 发现了一类新型广谱小分子抗病毒药物，其通过宿主导向机制发挥作用。这些化合物已展示出创新的作用机制，并针对几种具有商业价值的高优先级病原体。基于色烯酮的先导候选药物具有 nM 范围内的效力，在体外和动物模型中抑制多种病毒，包括流感、冠状病毒、西尼罗河、埃博拉和登革热病毒，具有有吸引力的药理学特征，并且在体内具有良好的耐受性。在此应用中，我们将执行先导化合物优化和 先导系列的临床前开发。该项目的主要里程碑是选择一种或多种提名候选药物进行正式的 IND 开发，以开发针对广泛呼吸道病毒感染的口服疗法。刺激宿主先天免疫反应的药物治疗作为一种治疗干预策略越来越受到重视，并有可能重新定义抗病毒药物开发的范式。对有效抗病毒药物的需求非常大，我们在存在多种病毒的情况下刺激先天免疫的方法 对抗措施已经产生了有希望的线索，可有效对抗多种 RNA 和 DNA 病毒。我们组建了一支高素质的开发团队，其中包括负责抗病毒发现工作的 Kineta 科学家和华盛顿大学的 Michael Gale, Jr. 教授，他是先天免疫和抗病毒反应方面的专家。