先导化合物发现

确定并验证与疾病相关的靶蛋白后,即可进行化合物筛选,通过激活或抑制小分子与特定的靶蛋白相互作用,鉴定药物发现所需的先导化合物。
推荐类别
为加快先导化合物发现进而加速药物发现,快速有效的筛选技术至关重要。高通量筛选(HTS)利用自动化和机械臂技术快速分析大型化合物文库,最终检测出最适合用作候选药物的化合物。DNA编码文库(DEL)筛选可实现小分子化合物与短DNA片段的质量缀合,因此可以同时检测更多分子的预期活性和功能。在基于结构的药物设计筛选中,可通过计算机模拟技术预测化合物的3D结构,即将整个文库中的化合物对接于结合位点上,并评估化合物与目标蛋白之间的空间和静电亲和力,然后针对排名最高的化合物进行进一步生物学测试。
Hit-to-lead(H2L)研究可评估苗头化合物的药效动力学、理化和药代动力学特性,以找出先导化合物,进行先导化合物优化,并进一步分析其作为药物开发候选药物的潜力。
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