Abstract：
BACKGROUND: Cancer has been recognized as one of the non-communicable diseases with an increasing number of new cases, higher morbidity, and higher mortality rates at the global level. Thus, there is non-stop search for novel targets and small molecules to improve the chemotherapeutic outcomes concerning potency, selectivity, efficiency, affinity, ADMET, etc. Among anticancer therapeutic targets, tyrosine kinase has been documented well and approved as an important target with the development of various clinically used drugs. There are several structurally diverse small molecules in different preclinical and clinical stages of development that act by affecting tyrosine kinases in cancerous cells. Here, we have summarized different potent molecules acting against tyrosine kinases that can be considered as anticancer agents.
OBJECTIVE: The current review focused on structural aspects of different chemical agents for inhibition of tyrosine kinases as anticancer agents.
METHODS: The present study provides a summarized review of published information on tyrosine kinase inhibitors, their binding pattern, potencies, and structure-activity relationships. The review also highlighted the structural aspects of the interaction between inhibitors and amino acid residues of tyrosine kinases. Moreover, it also provided a summary of different types of cancers and the currently available options for treatment.
RESULTS: Several studies are being conducted for the inhibition of different tyrosine kinases using small molecules for the treatment of cancer. Tyrosine kinases have been reported involving in routine cellular functions, growth, and division of cells through different pathways which depend on phosphorylation. The overexpression and uncontrolled activity of tyrosine kinases have been identified as an important feature of cancerous cells. Thus, various small molecules have been reported which inhibit tyrosine kinases to block the growth and division of cancer cells. Here, more than 30 highly potent inhibitors of tyrosine kinases are summarised, which consist of pyrimidine, pyrazole, triazine, quinazoline, quinoline, pyrazine, chromene, etc. rings as a basic skeleton with different substituents.
CONCLUSIONS: Inhibition of tyrosine kinases by different small molecules is an approved strategy for the development of novel anticancer agents. Several published reports have mentioned the characteristics of the different binding sites and crucial residues in tyrosine kinases for the design of novel molecular inhibitors. However, selectivity is an important criterion for the development of chemotherapeutic agents due to the existence of approximately 30 families of tyrosine kinases.
OBJECTIVE: The current review focused on structural aspects of different chemical agents for inhibition of tyrosine kinases as anticancer agents.
METHODS: The present study provides a summarized review of published information on tyrosine kinase inhibitors, their binding pattern, potencies, and structure-activity relationships. The review also highlighted the structural aspects of the interaction between inhibitors and amino acid residues of tyrosine kinases. Moreover, it also provided a summary of different types of cancers and the currently available options for treatment.
RESULTS: Several studies are being conducted for the inhibition of different tyrosine kinases using small molecules for the treatment of cancer. Tyrosine kinases have been reported involving in routine cellular functions, growth, and division of cells through different pathways which depend on phosphorylation. The overexpression and uncontrolled activity of tyrosine kinases have been identified as an important feature of cancerous cells. Thus, various small molecules have been reported which inhibit tyrosine kinases to block the growth and division of cancer cells. Here, more than 30 highly potent inhibitors of tyrosine kinases are summarised, which consist of pyrimidine, pyrazole, triazine, quinazoline, quinoline, pyrazine, chromene, etc. rings as a basic skeleton with different substituents.
CONCLUSIONS: Inhibition of tyrosine kinases by different small molecules is an approved strategy for the development of novel anticancer agents. Several published reports have mentioned the characteristics of the different binding sites and crucial residues in tyrosine kinases for the design of novel molecular inhibitors. However, selectivity is an important criterion for the development of chemotherapeutic agents due to the existence of approximately 30 families of tyrosine kinases.
摘要：
背景：随着新病例的增加，癌症已被认为是非传染性疾病之一，发病率较高，以及全球死亡率较高。因此，不断寻找新的靶标和小分子，以改善化疗效果有关的效力，选择性,效率,亲和力,ADMET,等。在抗癌治疗靶点中，随着各种临床使用药物的开发，酪氨酸激酶已被充分记录并被批准为重要靶标。在不同的临床前和临床发展阶段有几种结构上不同的小分子，它们通过影响癌细胞中的酪氨酸激酶起作用。这里,我们总结了不同的强效分子对抗酪氨酸激酶，这些分子可以被认为是抗癌剂。
目的：目前的综述集中在不同的化学试剂抑制酪氨酸激酶作为抗癌药物的结构方面。
方法：本研究概述了已发表的酪氨酸激酶抑制剂的信息，它们的结合模式，效力，和结构-活动关系。该综述还强调了抑制剂与酪氨酸激酶的氨基酸残基之间相互作用的结构方面。此外，它还概述了不同类型的癌症以及目前可用的治疗方案.
结果：正在进行一些研究，以使用小分子治疗癌症来抑制不同的酪氨酸激酶。据报道，酪氨酸激酶涉及常规细胞功能，增长,通过依赖于磷酸化的不同途径进行细胞分裂。酪氨酸激酶的过表达和不受控制的活性已被鉴定为癌细胞的重要特征。因此，已经报道了各种小分子抑制酪氨酸激酶以阻断癌细胞的生长和分裂。这里,总结了30多种高效酪氨酸激酶抑制剂，由嘧啶组成，吡唑,三嗪,喹唑啉，喹啉,吡嗪,色烯,等。环作为具有不同取代基的基本骨架。
结论：不同的小分子对酪氨酸激酶的抑制是开发新型抗癌药物的批准策略。一些公开的报道提到了酪氨酸激酶中不同结合位点和关键残基的特征，用于设计新型分子抑制剂。然而,由于存在大约30个酪氨酸激酶家族,选择性是开发化疗剂的重要标准。
目的：目前的综述集中在不同的化学试剂抑制酪氨酸激酶作为抗癌药物的结构方面。
方法：本研究概述了已发表的酪氨酸激酶抑制剂的信息，它们的结合模式，效力，和结构-活动关系。该综述还强调了抑制剂与酪氨酸激酶的氨基酸残基之间相互作用的结构方面。此外，它还概述了不同类型的癌症以及目前可用的治疗方案.
结果：正在进行一些研究，以使用小分子治疗癌症来抑制不同的酪氨酸激酶。据报道，酪氨酸激酶涉及常规细胞功能，增长,通过依赖于磷酸化的不同途径进行细胞分裂。酪氨酸激酶的过表达和不受控制的活性已被鉴定为癌细胞的重要特征。因此，已经报道了各种小分子抑制酪氨酸激酶以阻断癌细胞的生长和分裂。这里,总结了30多种高效酪氨酸激酶抑制剂，由嘧啶组成，吡唑,三嗪,喹唑啉，喹啉,吡嗪,色烯,等。环作为具有不同取代基的基本骨架。
结论：不同的小分子对酪氨酸激酶的抑制是开发新型抗癌药物的批准策略。一些公开的报道提到了酪氨酸激酶中不同结合位点和关键残基的特征，用于设计新型分子抑制剂。然而,由于存在大约30个酪氨酸激酶家族,选择性是开发化疗剂的重要标准。
