长循环酶激活的HSP90向的坎普托他辛衍生物
Mengyuan Ding1, Qianqian Shen2, Yi Su2
1Innovation Center for AI and Drug Discovery, School of Pharmacy, East China Normal University, 3663 North Zhongshan Road, Shanghai 200062, PR China; Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, 3663 North Zhongshan Road, Shanghai 200062, PR China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
研究人员开发了新的专蛋白结合前药物,以增强坎普托塞辛的输送. 这些药物输送系统提高了瘤向和抗癌疗效,同时减少了副作用,为癌症治疗提供了有前途的方法.
科学领域:
- 在瘤学瘤学.
- 药物运输 药物运输 药物运输
- 生物化学 生物化学
背景情况:
- 坎普托塞辛是强大的抗癌药物,其传递和毒性有限.
- 由酶激活的药物释放系统可以改善治疗结果.
- 提高药物循环时间和瘤选择性对于有效的癌症治疗至关重要.
研究的目的:
- 设计和评估一种新型的,用酶激活的,与白蛋白结合的,坎普托他衍生物 (AZ'0132) 的前药物.
- 研究这些新药物输送系统的瘤向能力和抗瘤疗效.
- 评估白蛋白结合对坎普托塞辛前药的药理学特性和毒性概况的影响.
主要方法:
- 使用氨酸-氨酸连接剂和AZ'0132,针对eHSP90.2的酶激活前药物 (HC07) 的构建.
- 通过将HC07与白蛋白结合,开发结合白蛋白前药物 (HC08和HC09).
- 在体内对前药物进行循环时间,瘤选择性和抗瘤疗效的评估.
主要成果:
- HC07通过eHSP90向瘤提供了有针对性的输送,特定的裂纹增强了治疗窗口并降低了眼部毒性.
- 专结合前药物HC08和HC09在体内循环时间延长.
- 与非约束性对应物相比,HC08和HC09显著改善了瘤选择性和增强了抗瘤功效.
结论:
- 开发的基于eHSP90的,与白蛋白结合的前期药物代表了对坎普托提辛的有希望的长期循环药物输送系统.
- 这一策略提供了一种新的方法来提高抗癌药物的疗效,并减少系统性毒性.
- 这些发现为设计未来抗癌疗法的先进药物输送系统提供了新的途径.
更多相关视频
07:47Custom-designed Laser-based Heating Apparatus for Triggered Release of Cisplatin from Thermosensitive Liposomes with Magnetic Resonance Image Guidance
Published on: December 13, 2015
06:00Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics
Published on: May 14, 2016
相关概念视频
Translocation of Proteins into the Mitochondria
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Energy to Drive Translocation
Generally, polypeptides are unfolded by two distinct...
Protein Transport to the Stroma
Protein complexes called the translocon of the outer chloroplast membrane or TOC complex, and the translocon of the inner chloroplast membrane or TIC complex mediate the...
The Unfolded Protein Response
ATP Driven Pumps II: P-type Pumps
A typical P-type pump has three cytosolic domains: nucleotide-binding (N), phosphorylation (P), and activator (A) domains. These domains are connected to the membrane-spanning helices by short amino acid segments. ATP hydrolysis and covalent phosphoenzyme intermediate formation are crucial parts of the catalytic cycle. At the highly...
Export of Misfolded Proteins out of the ER
