Dept of Medicinal Chemistry, DCRM Pharmacy College, JNT University, Inkollu 523167, Andhra Pradesh, India.
Mini Rev Med Chem. 2012 Feb;12(2):98-119. doi: 10.2174/138955712798995039.
Kinases are probably the most important signaling enzymes, which represent about 20% of the druggable genome. Currently, more than 150 kinases are known. So, kinase inhibition therapy has become a very important area of drug research since most of our diseases are related to intra or intercellular signaling by kinases. Indole alkaloids are extensively studied for their biological activities in several pharmaceutical areas, including, for example, antitumor. Among this chemical family, indolinone displays very promising antitumor properties by inhibiting various kinase families. These small molecules have a low molecular weight and most of them bind to protein kinases competing with ATP for the ATP-binding site. This review focuses on the indolinone based drugs approved for the treatment of cancer, drugs under clinical trial and then chemical diversity of various synthetic analogues of indolinone and their metabolites as various kinase inhibitors. This review also focused on structural activity relationship (SAR), mechanisms of action and biological targets through which indolinone and its derivatives display their antitumor activity.
激酶可能是最重要的信号酶，约占可成药基因组的 20%。目前已知的激酶超过 150 种。因此，激酶抑制疗法已成为药物研究的一个非常重要的领域，因为我们的大多数疾病都与激酶的细胞内或细胞间信号转导有关。吲哚生物碱因其在几个制药领域的生物活性而被广泛研究，例如抗肿瘤。在这个化学家族中，吲哚酮通过抑制各种激酶家族显示出非常有前途的抗肿瘤特性。这些小分子的分子量低，其中大多数与蛋白激酶结合，与 ATP 竞争 ATP 结合位点。本文综述了已批准用于治疗癌症的基于吲哚酮的药物、临床试验中的药物，以及各种吲哚酮及其代谢物的合成类似物的化学多样性及其作为各种激酶抑制剂的作用。本文还重点介绍了结构活性关系（SAR）、作用机制和生物靶点，通过这些靶点，吲哚酮及其衍生物发挥其抗肿瘤活性。
