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Repurposing of Acriflavine to Target Chronic Myeloid Leukemia Treatment
Current Medicinal Chemistry ( IF 4.1 ) Pub Date : 2021-03-31 , DOI: 10.2174/0929867327666200908114411
Rawan Nehme 1 , Rawan Hallal 1 , Maya El Dor 1 , Firas Kobeissy 2 , Fabrice Gouilleux 1 , Frédéric Mazurier 1 , Kazem Zibara 3
Affiliation  

Drug repurposing has lately received increasing interest in several diseases especially in cancers, due to its advantages in facilitating the development of new therapeutic strategies, by adopting a cost-friendly approach and avoiding the strict Food and Drug Administration (FDA) regulations. Acriflavine (ACF) is an FDA approved molecule that has been extensively studied since 1912 with antiseptic, trypanocidal, anti-viral, anti-bacterial and anti-cancer effects. ACF has been shown to block the growth of solid and hematopoietic tumor cells. Indeed, ACF acts as an inhibitor of various proteins, including DNA-dependent protein kinases C (DNA-PKcs), topoisomerase I and II, hypoxia-inducible factor 1α (HIF-1α), in addition to its recent discovery as an inhibitor of the signal transducer and activator of transcription (STAT). Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder characterized by the expression of the constitutively active tyrosine kinase BCR-ABL. This protein allows the activation of several signaling pathways known for their role in cell proliferation and survival, such as the JAK/STAT pathway. CML therapy, based on tyrosine kinase inhibitors (TKIs), such as imatinib (IM), is highly effective. However, 15% of patients are refractory to IM, where in some cases, 20-30% of patients become resistant. Thus, we suggest the repurposing of ACF in CML after IM failure or in combination with IM to improve the anti-tumor effects of IM. In this review, we present the different pharmacological properties of ACF along with its anti-leukemic effects in the hope of its repurposing in CML therapy.



中文翻译:

将cri黄素用于治疗慢性粒细胞白血病

通过采用成本友好的方法并避免采用严格的食品药品监督管理局(FDA)法规,药物重用有利于开发新的治疗策略,因此药物重用近来已引起人们对某些疾病(尤其是癌症)的日益增长的兴趣。Acriflavine(ACF)是FDA批准的分子,自1912年以来就进行了广泛的研究,具有防腐,锥虫,抗病毒,抗菌和抗癌作用。ACF已显示可阻止实体瘤和造血肿瘤细胞的生长。的确,ACF除了最近发现它是AFP的抑制剂外,还起着各种蛋白的抑制剂的作用,包括DNA依赖性蛋白激酶C(DNA-PKcs),拓扑异构酶I和II,低氧诱导因子1α(HIF-1α)。信号转导子和转录激活子(STAT)。慢性粒细胞白血病(CML)是一种克隆性骨髓增生性疾病,其特征在于组成性活性酪氨酸激酶BCR-ABL的表达。该蛋白可以激活一些在细胞增殖和存活中发挥作用的信号通路,例如JAK / STAT通路。基于酪氨酸激酶抑制剂(TKI),例如伊马替尼(IM)的CML治疗非常有效。但是,有15%的患者对IM无效,在某些情况下,有20-30%的患者变得耐药。因此,我们建议在IM失败后或与IM联合使用CCF中的ACF,以改善IM的抗肿瘤作用。在这篇综述中,我们介绍了ACF的不同药理特性及其抗白血病作用,以期将其重新用于CML治疗。该蛋白可以激活一些在细胞增殖和存活中发挥作用的信号通路,例如JAK / STAT通路。基于酪氨酸激酶抑制剂(TKI),例如伊马替尼(IM)的CML治疗非常有效。但是,有15%的患者对IM无效,在某些情况下,有20-30%的患者变得耐药。因此,我们建议在IM失败后或与IM联合使用CCF中的ACF,以改善IM的抗肿瘤作用。在这篇综述中,我们介绍了ACF的不同药理特性及其抗白血病作用,以期将其重新用于CML治疗。该蛋白可以激活一些在细胞增殖和存活中发挥作用的信号通路,例如JAK / STAT通路。基于酪氨酸激酶抑制剂(TKI),例如伊马替尼(IM)的CML治疗非常有效。但是,有15%的患者对IM无效,在某些情况下,有20-30%的患者变得耐药。因此,我们建议在IM失败后或与IM联合使用CCF中的ACF,以改善IM的抗肿瘤作用。在这篇综述中,我们介绍了ACF的不同药理特性及其抗白血病作用,以期将其重新用于CML治疗。如伊马替尼(IM),是非常有效的。但是,有15%的患者对IM无效,在某些情况下,有20-30%的患者变得耐药。因此,我们建议在IM失败后或与IM联合使用CCF中的ACF,以改善IM的抗肿瘤作用。在这篇综述中,我们介绍了ACF的不同药理特性及其抗白血病作用,以期将其重新用于CML治疗。如伊马替尼(IM),是非常有效的。但是,有15%的患者对IM无效,在某些情况下,有20-30%的患者变得耐药。因此,我们建议在IM失败后或与IM联合使用CCF中的ACF,以改善IM的抗肿瘤作用。在这篇综述中,我们介绍了ACF的不同药理特性及其抗白血病作用,以期将其重新用于CML治疗。

更新日期:2021-04-29
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