The method of cellular reprogramming using small molecules involves the manipulation of somatic cells to generate desired cell types under chemically limited conditions, thus avoiding the ethical controversy of embryonic stem cells and the potential hazards of gene manipulation. The combinations of small molecules and their effects on mouse and human somatic cells are similar. Several small molecules, including CHIR99021, 616452, A83-01, SB431542, forskolin, tranylcypromine and valproic acid [VPA], have been frequently used in reprogramming of mouse and human somatic cells. This indicated that the reprogramming approaches related to these compounds were essential. These approaches were mainly divided into four classes: epigenetic modification, signal modulation, metabolic modulation and senescent suppression. The structures and functions of small molecules involved in these reprogramming approaches have been studied extensively. Molecular docking gave insights into the mechanisms and structural specificities of various small molecules in the epigenetic modification. The binding modes of RG108, Bix01294, tranylcypromine and VPA with their corresponding proteins clearly illustrated the interactions between these compounds and the active sites of the proteins. Glycogen synthase kinase 3β [CHIR99021], transforming growth factor β [616452, A83-01 and SB431542] and protein kinase A [forskolin] signaling pathway play important roles in signal modulation during reprogramming, however, the mechanisms and structural specificities of these inhibitors are still unknown. Further, the numbers of small molecules in the approaches of metabolic modulation and senescent suppression were too few to compare. This review aims to serve as a reference for reprogramming through small molecules in order to benefit future regenerative medicine and clinical drug discovery.

使用小分子进行细胞重编程的方法涉及在化学有限的条件下操作体细胞以产生所需的细胞类型，从而避免胚胎干细胞的伦理争议和基因操作的潜在危害。小分子的组合及其对小鼠和人类体细胞的影响是相似的。几种小分子，包括 CHIR99021、616452、A83-01、SB431542、forskolin、反苯环丙胺和丙戊酸 [VPA]，已经常用于小鼠和人类体细胞的重编程。这表明与这些化合物相关的重编程方法是必不可少的。这些方法主要分为四类：表观遗传修饰、信号调节、代谢调节和衰老抑制。这些重编程方法中涉及的小分子的结构和功能已被广泛研究。分子对接使人们深入了解了表观遗传修饰中各种小分子的机制和结构特异性。RG108、Bix01294、反苯环丙胺和VPA与其相应蛋白质的结合模式清楚地说明了这些化合物与蛋白质活性位点之间的相互作用。糖原合酶激酶 3β [CHIR99021]、转化生长因子 β [616452、A83-01 和 SB431542] 和蛋白激酶 A [forskolin] 信号通路在重编程过程中的信号调节中起重要作用，但是，这些抑制剂的机制和结构特异性是还是未知数。更远，代谢调节和衰老抑制方法中的小分子数量太少，无法进行比较。本综述旨在作为通过小分子进行重编程的参考，以有利于未来的再生医学和临床药物发现。