Paul Leeson Consulting Ltd, The Malt House, Main Street, Congerstone, Nuneaton, Warkwickshire CV13 6LZ, United Kingdom.
European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SD, United Kingdom.
J Med Chem. 2021 Jun 10;64(11):7210-7230. doi: 10.1021/acs.jmedchem.1c00416. Epub 2021 May 13.
Physicochemical descriptors commonly used to define "drug-likeness" and ligand efficiency measures are assessed for their ability to differentiate marketed drugs from compounds reported to bind to their efficacious target or targets. Using ChEMBL version 26, a data set of 643 drugs acting on 271 targets was assembled, comprising 1104 drug-target pairs having ≥100 published compounds per target. Taking into account changes in their physicochemical properties over time, drugs are analyzed according to their target class, therapy area, and route of administration. Recent drugs, approved in 2010-2020, display no overall differences in molecular weight, lipophilicity, hydrogen bonding, or polar surface area from their target comparator compounds. Drugs are differentiated from target comparators by higher potency, ligand efficiency (LE), lipophilic ligand efficiency (LLE), and lower carboaromaticity. Overall, 96% of drugs have LE or LLE values, or both, greater than the median values of their target comparator compounds.
用于定义“类药性”和配体效率的物理化学描述符，用于评估其区分已上市药物与报告与有效靶标或靶标结合的化合物的能力。使用 ChEMBL 版本 26，组装了一个作用于 271 个靶标的 643 种药物的数据集，其中包含 1104 个药物-靶标对，每个靶标具有≥100 种已发表的化合物。考虑到它们的物理化学性质随时间的变化，根据靶标类别、治疗领域和给药途径对药物进行分析。2010-2020 年批准的最近的药物与它们的靶标比较化合物在分子量、脂溶性、氢键和亲水性表面积方面没有总体差异。药物与靶标比较化合物的区别在于更高的效力、配体效率（LE）、脂溶性配体效率（LLE）和更低的碳芳构性。总体而言，96%的药物具有大于其靶标比较化合物中位数的 LE 或 LLE 值或两者兼有。
