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FLT3抑制剂 1

亚甲基蓝 1

吉瑞替尼 1

奎扎替尼 1

实时成像 1

急性髓系白血病 1

泌尿系统 1

米哚妥林 1

索拉非尼 1

肾功能 1

近红外二区荧光 1

靶向治疗 1

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Synthesis and properties of water-soluble 1,9-dialkyl-substituted BF

Dan Wu, Gonzalo Durán-Sampedro, Donal F. O’Shea

《化学科学与工程前沿（英文）》 2020年第14卷第1期页码 97-104 doi: 10.1007/s11705-019-1828-x

摘要： Bis-alkylsulfonic acid and polyethylene glycol (PEG)-substituted BF azadipyrromethenes have been synthesized by an adaptable and versatile route. Only four synthetic stages were required to produce the penultimate fluorophore compounds, containing either two alcohol or two terminal alkyne substituents. The final synthetic step introduced either sulfonic acid or polyethylene glycol groups to impart aqueous solubility. Sulfonic acid groups were introduced by reaction of the bis-alcohol-substituted fluorophore with sulfur trioxide, and a double Cu(I)-catalyzed cycloaddition reaction between the bis-alkyne fluorophore and methoxypolyethylene glycol azide yielded a neutral bis-pegylated derivative. Both fluorophores exhibited excellent near-infrared (NIR) photophysical properties in methanol and aqueous solutions. Live cell microscopy imaging revealed efficient uptake and intracellular labelling of cells for both fluorophores. Their simple synthesis, with potential for last-step structural modifications, makes the present NIR-active azadipyrromethene derivatives potentially useful as NIR fluorescence imaging probes for live cells.

关键词： NIR-fluorophores live cell imaging NIR-AZA

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Near-infrared benzodiazoles as small molecule environmentally-sensitive fluorophores

《化学科学与工程前沿（英文）》 2022年第16卷第1期页码 128-135 doi: 10.1007/s11705-021-2080-8

摘要： The development of fluorophores emitting in the near-infrared spectral window has gained increased attention given their suitable features for biological imaging. In this work, we have optimised a general and straightforward synthetic approach to prepare a small library of near-infrared-emitting C-bridged nitrobenzodiazoles using commercial precursors. C-bridged benzodiazoles have low molecular weight and neutral character as important features that are not common in most near-infrared dyes. We have investigated their fluorescence response in the presence of a wide array of 60 different biomolecules and identified compound 3i as a potential chemosensor to discriminate between Fe²⁺ and Fe³⁺ ions in aqueous media.

关键词： fluorescence probes iron screening library

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抑制FLT3 ——急性髓系白血病分子靶向治疗的原型 Review

Rowe, Nir Weigert

《工程（英文）》 2021年第7卷第10期页码 1354-1368 doi: 10.1016/j.eng.2021.05.020

摘要：

急性髓系白血病（AML）的现代治疗始于1973年，首例柔红霉素和阿糖胞苷联合治疗法的成功随后拯救了大约45%的患者。准确的AML诊断依赖于形态学方法，其最初仅由细胞化学手段辅助。与急性淋巴细胞白血病（ALL）不同，至少在20世纪70年代和80年代，免疫分型在AML的诊断中几乎不起作用。可靠的细胞遗传学方法的出现为AML的预后发展带来了翻天覆地的变化。通过核型分析，可以对不同的AML实现分类与分层，以进行各种治疗。借助细胞上抗原标记物的免疫表型鉴定，独特的突变图谱可以里程碑式地进一步对 AML 患者进行分类。所有的这些进展都随着对肿瘤负荷[即微小残留病变（minimal residual disease, MRD）]的重要性的理解而成为AML患者管理的关键。MRD的疗效在过去10年迅速发展，其特异性从免疫分型的10^-3发展到聚合酶链反应（PCR）的10^-4（且仅对于部分AML患者有效），并最终在具有下一代测序（NGS）技术的灵敏度极高的细胞中发展至10^-5甚至10^-6。所有这些进步都促进了个性化医疗概念的发展，并带来了可以准确用于特定诊断亚型的靶向药物。可以精准预测与测量其响应。这些靶向药物现已成为AML管理的基础，其疗效显著提高，而毒性则显著下降。本文的重点是研究最为深入的AML靶向药物之一——FMS样酪氨酸激酶3（FLT3）抑制剂，它影响了AML的预后与治疗。作为已被批准的其他新兴靶向药物以及目前正在开发的靶向药物的原型，本文将选择性地对FLT3抑制剂展开详细讨论。

关键词：急性髓系白血病靶向治疗 FLT3抑制剂米哚妥林吉瑞替尼奎扎替尼索拉非尼

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Near-infrared fluorescent probe for fast track of cyclooxygenase-2 in Golgi apparatus in cancer cells

Bhaskar Gurram, Miao Li, Jiangli Fan, Jingyun Wang, Xiaojun Peng

《化学科学与工程前沿（英文）》 2020年第14卷第1期页码 41-52 doi: 10.1007/s11705-019-1796-1

摘要： Cyclooxygenase-2 (COX-2) has been used as an excellent traceable biomarker, and exists maximally in Golgi apparatus (Cancer cells). Celecoxib (CCB) is a selective inhibitor for COX-2, and has been used as one of non-steroidal anti-inflammatory drug. Herein we report the conjugation of nile blue (NB) with CCB via a six-carbon linkage to form a fluorescence probe NB-C6-CCB for the detection of COX-2. NB-C6-CCB displays strong fluorescence with the emission peak centered at near-infrared wavelength (700 nm) in tumor cells or tumor tissues with high expression of COX-2. Importantly, NB-C6-CCB can discriminate cancer cells (MCF-7) fluorescence intensity from normal ones (COS-7) in the co-culture medium under confocal microscope. Subcellular localization of the NB-C6-CCB preferentially points to the Golgi apparatus and increases the fluorescent intensity. The competitive analysis (with CCB) and Native-PAGE analysis confirmed that NB-C6-CCB shows selective binding affinity towards COX-2 enzyme. Competitive analysis with CCB (flow cytometry assay) revealed the fluorescence intensity fluctuation due to pretreatment of CCB with different concentrations, indicating that the NB-C6-CCB is a precise or sensitive probe for the COX-2. Tumor tissue (depth: 500 µm), organs and mice imaging tests show excellent near-infrared visualization, specific localization and identification of tumors.

关键词： cyclooxygenase-2 nile blue CCB Golgi apparatus NIR imaging

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基于临床可用的亚甲基蓝近红外二区成像用于泌尿系统结构及功能成像的研究 Article

薛丁玮, 吴迪, 陆泽毅, Jochen Neuhaus, 阿卜杜热合曼·则比布拉, 冯哲, 成晟, 周静, 钱骏, 李恭会

《工程（英文）》 2023年第22卷第3期页码 149-158 doi: 10.1016/j.eng.2021.07.032

摘要：近红外二区光谱区域（second nearinfrared spectral region, NIR-II, 1000~1700 nm）荧光生物成像相较于传统的荧光生物成像具有更高的空间分辨率、更深的穿透力和更好的信噪比在此，本文首次报道了基于临床可用且经肾脏排泄的荧光染料亚甲基蓝（methylene blue, MB）对活体泌尿系统进行NIR-II 荧光成像，该技术不仅可实现清晰的有创/无创尿路造影，而且还能有效且无创地检测肾功能以上研究结果表明MB辅助的NIR-II 荧光成像在临床/基础研究中泌尿系统结构和功能成像领域中具有较大的应用前景。

关键词：近红外二区荧光亚甲基蓝肾功能泌尿系统实时成像