In Vitro Evaluation of PARP1 Inhibitor Olaparib-Cyanine Dye Conjugate for the Treatment of Glioblastoma.

IF 3.4 4区医学 Q2 CHEMISTRY, MEDICINAL

ChemMedChem Pub Date : 2026-04-28 DOI:10.1002/cmdc.70286

Carina Dumo, Faheem, Peter J Choi, Nicholas J Pederson, Yuge Liu, Mike Dragunow, Thomas I-H Park, Katharine L Diehl, Jiney Jose

引用次数: 0

Abstract

Inhibition of DNA damage repair is a common mechanism to induce cancer cell death and, therefore, to treat cancers such as breast, prostate and ovarian cancer. This approach, although very attractive, has not been feasible for treating brain tumours due to the stringent structural features necessary for pharmaceutical agents to cross the blood-brain barrier (BBB). This study presents the proof of concept in vitro cellular activity of PARP1 (Poly(ADP-ribose) polymerase 1) enzyme inhibitor olaparib conjugated with a known BBB-crossing heptamethine cyanine dye. We also present evidence for cellular uptake and PARP1 inhibition by the conjugate, which contributes to the observed improvement in potency.

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PARP1抑制剂奥拉帕尼-菁染料偶联物治疗胶质母细胞瘤的体外评价。

抑制DNA损伤修复是诱导癌细胞死亡的常见机制，因此可以用于治疗乳腺癌、前列腺癌和卵巢癌等癌症。这种方法虽然很有吸引力，但由于药物通过血脑屏障（BBB）所必需的严格结构特征，这种方法在治疗脑肿瘤方面并不可行。本研究提出了PARP1 （Poly（adp -核糖）聚合酶1）酶抑制剂olaparib与已知的穿越bbb的七甲基菁染料偶联的体外细胞活性的概念证明。我们还提供了细胞摄取和PARP1抑制的证据，这有助于观察到的效力的改善。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ChemMedChem 医学-药学

CiteScore

6.70

自引率

2.90%

发文量

280

审稿时长

1 months

期刊介绍： Quality research. Outstanding publications. With an impact factor of 3.124 (2019), ChemMedChem is a top journal for research at the interface of chemistry, biology and medicine. It is published on behalf of Chemistry Europe, an association of 16 European chemical societies. ChemMedChem publishes primary as well as critical secondary and tertiary information from authors across and for the world. Its mission is to integrate the wide and flourishing field of medicinal and pharmaceutical sciences, ranging from drug design and discovery to drug development and delivery, from molecular modeling to combinatorial chemistry, from target validation to lead generation and ADMET studies. ChemMedChem typically covers topics on small molecules, therapeutic macromolecules, peptides, peptidomimetics, and aptamers, protein-drug conjugates, nucleic acid therapies, and beginning 2017, nanomedicine, particularly 1) targeted nanodelivery, 2) theranostic nanoparticles, and 3) nanodrugs. Contents ChemMedChem publishes an attractive mixture of: Full Papers and Communications Reviews and Minireviews Patent Reviews Highlights and Concepts Book and Multimedia Reviews.