Small Molecule Inhibitors Targeting the “Undruggable” Survivin: The Past, Present, and Future from a Medicinal Chemist’s Perspective

Cui, Qingbin; Huang, Caoqinglong; Liu, Jing-Yuan; Zhang, Jian-Ting

doi:10.1021/acs.jmedchem.3c01130

Cited by 5 publications

References 199 publications

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In Vitro and In Vivo Biological Evaluation of Novel 1,4‐Naphthoquinone Derivatives as Potential Anticancer Agents

Ravichandiran,

Martyna,

Kochanowicz

et al. 2024

ChemMedChem

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A novel library of naphthoquinone derivatives (3–5aa) was synthesized and evaluated for their anticancer properties. Specifically, compounds 5i, 5l, 5o, 5q, 5r, 5s, 5t, and 5v demonstrated superior cytotoxic activity against the cancer cell lines that were studied. Notably, compound 5v displayed a greater cytotoxic effect on MCF‐7 cells compared to the standard drug doxorubicin. To further investigate the mechanism of cytotoxic effect, additional anticancer studies were conducted with 5v in MCF‐7 cells. The findings showed that 5v triggered cytotoxic effects in MCF‐7 cells through the initiation of cell cycle arrest at the G1/S phase and necrosis. In vivo ecotoxicity studies indicated that 5v had lower toxicity towards zebrafish larvae (LC50 = 50.15 μM) and had an insignificant impact on cardiac functions. In vivo xenotransplantation of MCF‐7 cells in zebrafish larvae demonstrated a significant reduction in tumour volume in the xenograft. Approximately 95% of the zebrafish larvae with 5v xenografts survived after 10 days of the treatment. Finally, a computational modelling study was conducted on four protein receptors, namely ER, EFGR, BRCA1, and VEFGR2. The findings highlight the importance of the aminonaphthoquinone moiety, amide linkage, and propyl thio moiety in enhancing the anticancer properties.

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In Vitro and In Vivo Biological Evaluation of Novel 1,4‐Naphthoquinone Derivatives as Potential Anticancer Agents

Ravichandiran,

Martyna,

Kochanowicz

et al. 2024

ChemMedChem

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Expanding the ligand spaces for E3 ligases for the design of protein degraders

Shah Zaib Saleem,

Schwalm,

Knapp

2024

Bioorganic & Medicinal Chemistry

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Perovskite Probe-Based Machine Learning Imaging Model for Rapid Pathologic Diagnosis of Cancers

Chi,

Xue,

Zhou

et al. 2024

ACS Nano

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Accurately distinguishing tumor cells from normal cells is a key issue in tumor diagnosis, evaluation, and treatment. Fluorescence-based immunohistochemistry as the standard method faces the inherent challenges of the heterogeneity of tumor cells and the lack of big data analysis of probing images. Here, we have demonstrated a machine learning-driven imaging method for rapid pathological diagnosis of five types of cancers (breast, colon, liver, lung, and stomach) using a perovskite nanocrystal probe. After conducting the bioanalysis of survivin expression in five different cancers, highefficiency perovskite nanocrystal probes modified with the survivin antibody can recognize the cancer tissue section at the single cell level. The tumor to normal (T/N) ratio is 10.3fold higher than that of a conventional fluorescent probe, which can successfully differentiate between tumors and adjacent normal tissues within 10 min. The features of the fluorescence intensity and pathological texture morphology have been extracted and analyzed from 1000 fluorescence images by machine learning. The final integrated decision model makes the area under the receiver operating characteristic curve (area under the curve) value of machine learning classification of breast, colon, liver, lung, and stomach above 90% while predicting the tumor organ of 92% of positive patients. This method demonstrates a high T/N ratio probe in the precise diagnosis of multiple cancers, which will be good for improving the accuracy of surgical resection and reducing cancer mortality.

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Small Molecule Inhibitors Targeting the “Undruggable” Survivin: The Past, Present, and Future from a Medicinal Chemist’s Perspective

Cited by 5 publications

References 199 publications

In Vitro and In Vivo Biological Evaluation of Novel 1,4‐Naphthoquinone Derivatives as Potential Anticancer Agents

In Vitro and In Vivo Biological Evaluation of Novel 1,4‐Naphthoquinone Derivatives as Potential Anticancer Agents

Expanding the ligand spaces for E3 ligases for the design of protein degraders

Perovskite Probe-Based Machine Learning Imaging Model for Rapid Pathologic Diagnosis of Cancers

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