Unlocking the Potential of HK2 in Cancer Metabolism and Therapeutics

doi:10.2174/0929867326666181213092652
摘要

糖酵解是一个严格调节的过程，在此过程中，多种酶（例如己糖激酶（HK））发挥着关键作用。癌细胞的特征是几种同工酶在不同代谢途径中的特异性表达水平，这些特征为治疗性干预提供了可能性。在多种类型的癌症中，一直都报道过HKs（大多数是HK2亚型）的过表达。此外，在动物模型中，HK2的缺失已显示出可减少癌细胞的增殖而没有明显的副作用，这表明靶向HK2是癌症治疗的可行策略。 HK2抑制作用会导致糖酵解作用的实质性降低，从而影响中央代谢的多种途径，并且还会破坏线粒体外膜的稳定性，最终增强细胞死亡。尽管糖酵解抑制取得了有限的成功，部分是由于对特定同工型的选择性低以及已报道的HK抑制剂的过度副作用，但仍有足够的进展基础。目前的审查集中在HK2抑制，设想开发有效的和选择性的抗癌药。介绍了有关HKs的功能，表达和活性的信息，以及它们的结构，已知的抑制剂以及报告的HK2消融/抑制作用。讨论了不同同工酶的结构特征，旨在激发一种更合理的方法来设计具有适当药物样性质的选择性HK2抑制剂。特别注意结构相似的HK1和HK2同工型的结构和序列比较，旨在揭示可以在治疗上探索的差异。最后，对最近归因于HK2的几种不同途径和疾病的其他催化作用和非催化作用进行了综述，并简要讨论了它们的含义。
关键词: 己糖激酶（HK），癌症代谢，癌症治疗，糖酵解，药物开发，催化和非催化作用。
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DOI https://dx.doi.org/10.2174/0929867326666181213092652	Print ISSN 0929-8673
Publisher Name Bentham Science Publisher	Online ISSN 1875-533X
当代药物化学

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当代药物化学

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