Natural HSP90 inhibitors as a potential therapeutic intervention in treating cancers: A comprehensive review

Liew, Hui Yi; Tan, Xin Yoong; Chan, Hong Hao; Khaw, Kooi Yeong; Ong, Yong Sze

doi:10.1016/j.phrs.2022.106260

Cited by 12 publications

(8 citation statements)

References 94 publications

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“…Hsp90 upregulation in malignancies acts as protective for tumorigenesis, therefore Hsp90 inhibition is one of the trend cancer treatment modalities. Geldanamycin has been used in numerous cancer studies as gall bladder, thyroid, liver, osteosarcoma, lungs, melanoma, cervical, breast, prostate, colorectal cancers [37][38][39][40]. Germano et al emphasized that Ron can gain tumorigenic potential by single point mutations and aberrant activation of Ron has been determined in colorectal adenocarcinomas, non-small cell lung tumors and primary breast carcinomas.…”

Section: Discussionmentioning

confidence: 99%

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Drug repurposing analysis with co-expressed genes identifies novel drugs and small molecules for bladder cancer

Göv,

Kaynak Bayrak

2024

Journal of Scientific Reports-A

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Bladder cancer (BC) is the fifth most common malignancy in humans and has poor survival rates. Although there is extensive research on the diagnosis and treatment of BC, novel molecular therapies are essential due to tumor recurrence. In this study, we aim to identify repurposed drugs or small molecules of BC with multi-omics systems biology perspective. Gene expression datasets were statistically analyzed by comparing bladder tumor and normal bladder tissues and differentially expressed genes (DEGs) were determined. Co-expression network of common DEGs for BC was constructed and co-expressed module was found by using tumors and control bladder tissues. Using independent data, we demonstrated the high prognostic capacity of the module genes. Moreover, repurposed drugs or small molecules were predicted by using L1000CDS2 gene expression based-search engine tool. We found numerous drug candidates as 480743.cdx, MK-2206, Geldanamycin, PIK-90, BRD-K50387473 (XMD8-92), BRD-K96144918 (mead acid), Vorinostat, PLX-4720, Entinostat, BIX-01294, PD-0325901 and Selumetinib, that may be used in BC therapy. We report 480743.cdx, BRD-K50387473 (XMD8-92) and mead acid as novel drugs or small molecules that offer crucial step in translational cancer research of BC.

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Section: Discussionmentioning

confidence: 99%

“…Karkoulis et al, demonstrated anti-neoplastic properties of geldanamycin in human bladder tumor cell lines (RT4 and T24) [42]. Unfortunately, it is instable, cardiotoxic, oculotoxic, hepatotoxic and has low aqueous dissolubility, therefore several GA analogues have been produced [39,43].…”

Section: Discussionmentioning

confidence: 99%

Drug repurposing analysis with co-expressed genes identifies novel drugs and small molecules for bladder cancer

Göv,

Kaynak Bayrak

2024

Journal of Scientific Reports-A

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“… 53 In a review conducted by Liew and colleagues, several studies have shown that terpenoids, the group of compounds to which momordicine II belong, possess HSP90 inhibitory activities in cancer cell lines. 54 …”

Section: Discussionmentioning

confidence: 99%

Applying Network Pharmacology and Molecular Docking in the Screening for Molecular Mechanisms of Ampalaya (Momordica charantia L.) and Banaba (Lagerstroemia speciosa L.) against Type 2 Diabetes Mellitus

2023

Acta Med Philipp

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Background and Objectives Type 2 diabetes mellitus (T2DM) is a global health concern affecting more than 400 million people worldwide. Diabetic neuropathy, nephropathy, retinopathy, and cardiovascular complications lead to debilitating effects to patients. To prevent these, the treatment goal is to lower the blood sugar levels and maintain at a normal range which is achieved through conventional treatments like insulin and oral hypoglycemic agents. However, the high cost of these medications implicates patient treatment outcomes. Hence, alternatives are sought for including the use of herbal medicines. Momordica charantia (MC) and Lagerstroemia speciosa (LS) are common herbal medicines used to manage T2DM. In the Philippines, these herbal preparations are validated for their glucose lowering effects and are commonly found in combination in food supplements. The study aims to screen the possible mechanisms of compounds present in these herbal medicines which can offer possible explanations for their synergistic effects and rationalization of their combination in preparations. Methods Network pharmacology was employed to determine pivotal proteins that are targeted by MC and LS compounds. Molecular docking was then done to evaluate the favorability of the binding of these compounds toward their target proteins. Results Our results showed that TNF, HSP90AA1, MAPK3, ALDH2, GCK, AKR1B1, TTR and RBP4 are the possible pivotal targets of MC and LS compounds in T2DM. Conclusion Terpenoids from MC and decanoic acid from LS are the compounds which showed favorable binding towards pivotal protein targets in T2DM. By binding towards the different key proteins in T2DM, they may exhibit their synergistic effects. However, the results of this study are bound to the limitations of computational methods and experimental validation are needed to verify our findings.

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“…N-terminal Hsp90 inhibitors are categorized into natural and synthetic compounds with promising therapeutic results in preclinical or clinical studies [17][18][19] . The first generation of natural Hsp90 inhibitors includes Geldanamycin (GM) and its analogues (17-AAG and 17-DMAG), Novobiocin, and Radicicol 20,21 . Moreover, several synthesized compounds act as Hsp90 inhibitors 22 ; these organic compounds include PU3, pyrazole, indazole, aminoquinoline triazine, and isoxazole scaffolds [23][24][25][26][27] .…”

Section: Introductionmentioning

confidence: 99%

Design, synthesis and biological evaluation of new isoxazole derivatives as Hsp90 inhibitors

keshavarzipour,

Abbasi,

Khorsandi

et al. 2024

Preprint

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Heat shock protein 90 (Hsp90), a molecular chaperone, contributes to the preservation of folding, structure, stability, and function proteins. In this study, novel compounds comprising isoxazole structure were designed, synthesized and their potential ability as Hsp90 inhibitors was validated through docking studies. The active site-based compounds were prepared through a multi-step synthesis process and their chemical structures were characterized employing FT-IR, NMR, and mass spectrometry analysis. Cytotoxic and Hsp90 inhibition activities of synthesized compounds were assessed by MTT assay and ELISA kit, respectively. Based on the obtained results, compound 5 was the most cytotoxic derivative (IC50; 14 µM) against cancer cells and reduced Hsp90 expression from 5.54 ng/ml in untreated (normal cells) to 1.56 ng/ml in cancer cells. Moreover, molecular dynamics (MD) simulation results indicated its high affinity to target protein and approved its excellent stability which is essential for exerting an inhibitory effect on cancer cell proliferation.

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Natural HSP90 inhibitors as a potential therapeutic intervention in treating cancers: A comprehensive review

Cited by 12 publications

References 94 publications

Drug repurposing analysis with co-expressed genes identifies novel drugs and small molecules for bladder cancer

Drug repurposing analysis with co-expressed genes identifies novel drugs and small molecules for bladder cancer

Applying Network Pharmacology and Molecular Docking in the Screening for Molecular Mechanisms of Ampalaya (Momordica charantia L.) and Banaba (Lagerstroemia speciosa L.) against Type 2 Diabetes Mellitus

Design, synthesis and biological evaluation of new isoxazole derivatives as Hsp90 inhibitors

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