Research Collaboratory for Structural Bioinformatics Protein Data Bank, Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
Drug Discov Today. 2020 May;25(5):837-850. doi: 10.1016/j.drudis.2020.02.002. Epub 2020 Feb 14.
Open access to 3D structure information from the Protein Data Bank (PDB) facilitated discovery and development of >90% of the 79 new antineoplastic agents (54 small molecules, 25 biologics) with known molecular targets approved by the FDA 2010-2018. Analyses of PDB holdings, the scientific literature and related documents for each drug-target combination revealed that the impact of public-domain 3D structure data was broad and substantial, ranging from understanding target biology (∼95% of all targets) to identifying a given target as probably druggable (∼95% of all targets) to structure-guided lead optimization (>70% of all small-molecule drugs). In addition to aggregate impact assessments, illustrative case studies are presented for three protein kinase inhibitors, an allosteric enzyme inhibitor and seven advanced-stage melanoma therapeutics.
公共获取蛋白质数据库（PDB）中的 3D 结构信息，促进了 >90%的新型抗肿瘤药物（54 个小分子，25 个生物制剂）的发现和开发，这些药物的分子靶点均已得到 FDA 的批准，时间为 2010 年至 2018 年。对 PDB 持有的、与每种药物-靶标组合相关的科学文献和文件的分析表明，公共领域 3D 结构数据的影响广泛而深远，从了解靶标生物学（∼95%的所有靶标）到确定某个特定靶标可能具有成药性（∼95%的所有靶标），再到结构指导的先导化合物优化（>70%的所有小分子药物）。除了总体影响评估，还提供了三个蛋白激酶抑制剂、一个变构酶抑制剂和七个晚期黑色素瘤治疗药物的实例研究。
