小分子

小分子（英语：small molecule）是一个有机化学概念。一般将分子量小于900道尔顿的有机化合物分子称为小分子^[1]。小分子的直径以纳米计。目前大部分药物都是小分子类药物，蛋白质、核酸等生物大分子的基本组成单位（如氨基酸、核糖核苷酸、脱氧核苷酸）也是小分子。

小分子药物一般是抑制剂，通过干扰蛋白间相互作用起效^[2]。

药理学

目前大部分的药物都是小分子药物^[3] 。小分子的分子量上限一般设在900道尔顿。这是因为900道尔顿以下的分子在人体内能较快速地扩散进入细胞，到达作用靶点^[1][4]。根据里宾斯基五规则，口服给药的小分子药物的分子量最好能低于500道尔顿，否则损耗率会出现明显上升^[5][6]。

参见

• 大分子、生物大分子
• 前药

参考资料

1. Macielag MJ. Chemical properties of antibacterials and their uniqueness. Dougherty TJ, Pucci MJ (编). Antibiotic Discovery and Development. 2012: 801–2 [2020-01-16]. ISBN 978-1-4614-1400-1. （原始内容存档于2020-08-18）. The majority of [oral] drugs from the general reference set have molecular weights below 550. In contrast the molecular-weight distribution of oral antibacterial agents is bimodal: 340–450 Da but with another group in the 700–900 molecular weight range.
2. Arkin MR, Wells JA. Small-molecule inhibitors of protein-protein interactions: progressing towards the dream. Nature Reviews Drug Discovery. April 2004, 3 (4): 301–17. PMID 15060526. doi:10.1038/nrd1343.
3. Samanen J. Chapter 5.2 How do SMDs differ from biomolecular drugs?. Ganellin CR, Jefferis R, Roberts SM (编). Introduction to Biological and Small Molecule Drug Research and Development: theory and case studies Kindle. New York: Academic Press. 2013: 161–203 [2020-01-16]. ISBN 978-0-12-397176-0. doi:10.1016/B978-0-12-397176-0.00005-4. （原始内容存档于2020-09-02）. Table 5.13: Route of Administration: Small Molecules: oral administration usually possible; Biomolecules: Usually administered parenterally
4. Veber DF, Johnson SR, Cheng HY, Smith BR, Ward KW, Kopple KD. Molecular properties that influence the oral bioavailability of drug candidates. J. Med. Chem. 2002, 45 (12): 2615–23. PMID 12036371. doi:10.1021/jm020017n.
5. Lipinski CA. Lead-and drug-like compounds: the rule-of-five revolution. Drug Discovery Today: Technologies. 2004, 1 (4): 337–341. PMID 24981612. doi:10.1016/j.ddtec.2004.11.007.
6. Leeson PD, Springthorpe B. The influence of drug-like concepts on decision-making in medicinal chemistry. Nature Reviews Drug Discovery. 2007, 6 (11): 881–90. PMID 17971784. doi:10.1038/nrd2445.