Protein Kinases (PKs) are a heterogeneous family of enzymes that modulate several biological pathways, including cell division, cytoskeletal rearrangement, differentiation and apoptosis. In particular, due to their crucial role during human tumorigenesis and cancer progression, PKs are ideal targets for the design and development of effective and low toxic chemotherapeutics and represent the second group of drug targets after G-protein-coupled receptors. Nowadays, several compounds have been claimed to be PKs inhibitors, and some of them, such as imatinib, erlotinib and gefitinib, have already been approved for clinical use, whereas more than 30 others are in various phases of clinical trials. Among them, some natural or synthetic carbazole-based molecules represent promising PKs inhibitors due to their capability to interfere with PK activity by different mechanisms of action including the ability to act as DNA intercalating agents, interfere with the activity of enzymes involved in DNA duplication, such as topoisomerases and telomerases, and inhibit other proteins such as cyclindependent kinases or antagonize estrogen receptors. Thus, carbazoles can be considered a promising this class of compounds to be adopted in targeted therapy of different types of cancer.

中文翻译：

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咔唑衍生物作为靶向激酶的癌症治疗抑制剂。

蛋白激酶（PKs）是酶的异质家族，可调节几种生物学途径，包括细胞分裂，细胞骨架重排，分化和凋亡。特别地，由于其在人类肿瘤发生和癌症发展过程中的关键作用，PKs是设计和开发有效且低毒化学疗法的理想靶标，并且代表了G蛋白偶联受体之后的第二组药物靶标。如今，一些化合物被宣称是PKs抑制剂，其中一些化合物（例如伊马替尼，厄洛替尼和吉非替尼）已获准用于临床，而其他30多个化合物则处于临床试验的各个阶段。其中，一些天然或合成的咔唑类分子代表了有前途的PKs抑制剂，因为它们通过不同的作用机制干扰PK活性的能力，包括充当DNA嵌入剂的能力，干扰与DNA复制有关的酶（例如拓扑异构酶）的活性。和端粒酶，并抑制其他蛋白，例如细胞周期蛋白依赖性激酶或拮抗雌激素受体。因此，咔唑被认为是有望用于不同类型癌症的靶向治疗的这类化合物。