Do Biologically Relevant Compounds Have More Chance To Be Drugs?
Do Biologically Relevant Compounds Have More Chance To Be Drugs?
复制标题
DOI：
10.1021/ci900229c
复制
发表时间：
2009-10-01
影响因子：
5.6
通讯作者：
Zhang, Hong-Yu
中科院分区：
文献类型：
--
作者：
Kong, De-Xin;Ren, Wei;Zhang, Hong-Yu
为了证明内源性化合物/片段在药物发现和开发中的先天优势，提出了一种称为生物相关性（BR）的新指标。结果清楚地表明，它能够区分合成化学品，生物活性化合物，候选药物和上市药物。首先，所调查的数据库的平均BR按DNP > CMC > ACD-3D > MDDR的顺序降低。第二，对于具有相同生物活性的化合物，药物（CMC）具有比其候选物（MDDR）更高的平均BR。这些结果表明，具有更高BR的化合物有更多的机会在药物开发管道中生存下来。第三，上述结论得到了以下事实的支持，即后期开发阶段的化合物比早期开发阶段的化合物具有更高的BR。将BR与毒性、类药性和天然产物类性等指标进行比较。
To prove the innate advantages of endogenous compounds/fragments for drug discovery and development, a novel index termed biological relevance (BR) is proposed. The results clearly indicate its ability to distinguish between synthetic chemicals, bioactive compounds, drug candidates, and launched drugs. Primarily, the average BR of the databases investigated decreases in the order DNP > CMC > ACD-3D > MDDR. Second, for compounds with the same bioactivity, drugs (CMC) possess higher average BR than their candidates (MDDR). These results suggest that compounds with higher BR have more chance to survive the drug development pipeline. Third, the above conclusion is supported by the fact that compounds in the later development phases possess higher BR than those in the earlier phases. Comparisons were made between BR and other indices, including toxicity, druglikeness, and natural product] ikeness.