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专利述评:L-天冬酰胺酶在治疗急性淋巴细胞白血病中的应用

A Patent Review on the Use of L-Asparaginase in the Treatment of Acute Lymphocytic Leukemia.

机构信息

Department of Biotechnology, Universidade Estadual do Ceará, Fortaleza, Brazil.

Department of Biochemistry, Universidade Federal do Ceara, Fortaleza, Brazil.

出版信息

Recent Adv Drug Deliv Formul. 2021;15(1):37-45. doi: 10.2174/1872211314666210301125843.

Abstract

L-asparaginase (L-asparagine amino hydrolase, E.C.3.5.1.1) is the most important chemotherapeutic drug used in treating Acute Lymphocytic Leukemia (ALL), decreasing blood asparagine rates causing apoptosis in tumor cells. However, pharmacological drugs cause several side effects making treatments difficult. Thus, searches for new sources of L-asparaginase or enzyme modifications focus on discovering new products to use in therapy. This article reviewed published patents from 2000 to 2020 related to the treatment of ALL using L-asparaginase. Many organisms have been shown as potential viable L-asparaginase producers for use in the treatment of ALL. However, this patent review shows that few of these organisms are gaining attention to becoming bioproducts for the market. It is expected that drugs in the testing phase and patents related to the treatment of ALL and other cancers will become real products. Besides, a treatment using an amino acid depletion approach, now referring to asparagine, altogether with a compound that directly interferes with the expression of the asparagine synthase gene, is more suitable for the treatment of ALL and possibly to other cancers.

摘要

L-天冬酰胺酶(L-天冬酰胺氨基水解酶,EC3.5.1.1)是治疗急性淋巴细胞白血病(ALL)中最重要的化疗药物,可降低血液中天冬酰胺的水平,导致肿瘤细胞凋亡。然而,药理药物会引起多种副作用,使治疗变得困难。因此,寻找新的 L-天冬酰胺酶来源或酶修饰的研究重点是发现新的产品用于治疗。本文综述了 2000 年至 2020 年期间与使用 L-天冬酰胺酶治疗 ALL 相关的已发表专利。许多生物体已被证明是治疗 ALL 的潜在可行 L-天冬酰胺酶生产菌。然而,本专利综述表明,这些生物体中只有少数受到关注,成为市场上的生物制品。预计处于测试阶段的药物以及与 ALL 和其他癌症治疗相关的专利将成为现实产品。此外,使用氨基酸耗竭方法(现在称为天冬酰胺)与直接干扰天冬酰胺合成酶基因表达的化合物联合治疗 ALL 可能更适合治疗 ALL 以及其他癌症。

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