使用人工智能识别打击化合物,用于管理过敏疾病
Junhyoung Byun1,2, Junhu Tai1, Byoungjae Kim1,3
1Department of Otorhinolaryngology-Head & Neck Surgery, College of Medicine, Korea University, 02842 Seoul, Republic of Korea.
International journal of molecular sciences
|February 24, 2024
概括
研究人员确定了针对过敏性鼻炎 (AR) 的细胞因子信号传递3抑制剂 (SOCS3) 的新型候选药物. 化合物5和8在恢复JAK2活性和缓解AR症状方面显示出有希望的非临床疗效.
科学领域:
- 药理学 药理学是指药理学的学科.
- 免疫学 免疫学 免疫学
- 药物发现 药物发现 药物发现
背景情况:
- 过敏性鼻炎 (AR) 是一种普遍的疾病,通常通过具有局限性的疗法来管理.
- 细胞因子信号传递3抑制剂 (SOCS3) 在与AR相关的炎症途径中起作用.
- 准SOCS3的激酶抑制区域是一个潜在的治疗策略.
研究的目的:
- 识别和评估针对SOCS3进行AR治疗的候选药物.
- 在AR的临床前模型中研究新型化合物的疗效.
- 探索已识别的候选药物的作用机制.
主要方法:
- 基于人工智能 (AI) 的虚拟查以识别SOCS3抑制剂.
- 发光测试以评估JAK-2活动恢复.
- 基于细胞的测定 (Jurkat T,BEAS-2B) 来评估SOCS3,STAT3表达和酸化.
- 在体内研究中,使用OVA诱导的AR小鼠模型测量IgE,细胞因子和乙素.
主要成果:
- 人工智能选确定了20种具有强烈结合亲和力的命中化合物.
- 化合物5和8有效地恢复了JAK-2的活性,没有毒性.
- 这些化合物降低了SOCS3的表达,并使细胞系中的STAT3酸化正常化.
- 在体内,化合物5和8缓解了AR症状,并减少了关键的免疫标志物.
结论:
- 针对SOCS3的新型候选药物显示出对AR有前途的非临床疗效.
- 由人工智能驱动的药物发现平台成功识别了强大的治疗剂.
- 准SOCS3为管理过敏性鼻炎提供了一个创新的策略.
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