Histone deacetylase (HDAC) inhibitors in cancer: a patent review (2017-present)

Zhao, Cui; Dong, Hang; Xu, Qifu; Zhang, Yingjie

doi:10.1080/13543776.2020.1725470

Cited by 101 publications

(76 citation statements)

References 59 publications

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“…Here, we will briefly outline the four types of pan-inhibitors. More pan-inhibitor development can be found in several recent reviews [ 5 , 28 , 99 , 104 ].…”

Section: Pan-inhibitorsmentioning

confidence: 99%

“…Additionally, HDACs can indirectly regulate other post-translational modifications (PTMs) through releasing acetyl group from lysine so that other PTMs, for instance, ubiquitination, can mark on the loci [ 1 ]. So far, 18 human HDACs have been identified according to their sequence homologies to yeast and are divided into four classes: Class I (HDAC1-3 and 8), Class II with two subclasses (Class IIa includes HDAC4, 5, 7 and 9 and Class IIb corresponds to HDAC6 and 10) and Class IV (HDAC11) are zinc-dependent enzymes (also referred to as classical HDACs family), while Class III are NAD + -dependent which called sirtuins (SIRT1-7) [ 4 , 5 ]. Each class has different biological functions [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

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Structure-Based Inhibitor Discovery of Class I Histone Deacetylases (HDACs)

Luo

2020

IJMS

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Class I histone deacetylases (HDACs) are promising targets for epigenetic therapies for a range of diseases such as cancers, inflammations, infections and neurological diseases. Although six HDAC inhibitors are now licensed for clinical treatments, they are all pan-inhibitors with little or no HDAC isoform selectivity, exhibiting undesirable side effects. A major issue with the currently available HDAC inhibitors is that they have limited specificity and target multiple deacetylases. Except for HDAC8, Class I HDACs (1, 2 and 3) are recruited to large multiprotein complexes to function. Therefore, there are rising needs to develop new, hopefully, therapeutically efficacious HDAC inhibitors with isoform or complex selectivity. Here, upon the introduction of the structures of Class I HDACs and their complexes, we provide an up-to-date overview of the structure-based discovery of Class I HDAC inhibitors, including pan-, isoform-selective and complex-specific inhibitors, aiming to provide an insight into the discovery of additional HDAC inhibitors with greater selectivity, specificity and therapeutic utility.

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“…Here, we will briefly outline the four types of pan-inhibitors. More pan-inhibitor development can be found in several recent reviews [ 5 , 28 , 99 , 104 ].…”

Section: Pan-inhibitorsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Structure-Based Inhibitor Discovery of Class I Histone Deacetylases (HDACs)

Luo

2020

IJMS

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“…In the last decades, increasing evidence has associated epigenetic dysregulation with the development and progression of many diseases, including cancer [10][11][12]. For instance, transcriptional upregulation of HDACs was observed in colorectal, pancreatic, lung, gastric, prostate, and ovarian cancer [13][14][15]. In particular, HDAC 7 was overexpressed in breast cancer [16].…”

Section: Introductionmentioning

confidence: 99%

“…Specifically, numerous HDACis showed promising anticancer activities, related to their ability to suppress and induce apoptosis in Michigan Cancer Foundation-7 (MCF-7) breast cancer cell lines [18][19][20]. Overall, HDACis decrease cellular proliferation, induce cell death, apoptosis, and differentiation [15,21]. Despite their promising anticancer potential, severe side effects and toxicities, including thrombocytopenia, neutropenia, vomiting, and diarrhea, resulting from a non-selective inhibition towards various HDACs isoforms, are also documented [4,15].…”

Section: Introductionmentioning

confidence: 99%

“…Overall, HDACis decrease cellular proliferation, induce cell death, apoptosis, and differentiation [15,21]. Despite their promising anticancer potential, severe side effects and toxicities, including thrombocytopenia, neutropenia, vomiting, and diarrhea, resulting from a non-selective inhibition towards various HDACs isoforms, are also documented [4,15]. In this context, the development of new class-or isoform-selective HDACis with improved risk-benefit profiles as anticancer agents is an urgent need.…”

Section: Introductionmentioning

confidence: 99%

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Natural Products Extracted from Fungal Species as New Potential Anti-Cancer Drugs: A Structure-Based Drug Repurposing Approach Targeting HDAC7

et al. 2020

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Mushrooms can be considered a valuable source of natural bioactive compounds with potential polypharmacological effects due to their proven antimicrobial, antiviral, antitumor, and antioxidant activities. In order to identify new potential anticancer compounds, an in-house chemical database of molecules extracted from both edible and non-edible fungal species was employed in a virtual screening against the isoform 7 of the Histone deacetylase (HDAC). This target is known to be implicated in different cancer processes, and in particular in both breast and ovarian tumors. In this work, we proposed the ibotenic acid as lead compound for the development of novel HDAC7 inhibitors, due to its antiproliferative activity in human breast cancer cells (MCF-7). These promising results represent the starting point for the discovery and the optimization of new HDAC7 inhibitors and highlight the interesting opportunity to apply the “drug repositioning” paradigm also to natural compounds deriving from mushrooms.

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A Nuclear‐Targeted AIE Photosensitizer for Enzyme Inhibition and Photosensitization in Cancer Cell Ablation

et al. 2022

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The nucleus is considered the ideal target for anti-tumor therapy because DNA and some enzymes in the nucleus are the main causes of cell canceration and malignant proliferation. However, nuclear target drugs with good biosafety and high efficiency in cancer treatment are rare. Herein, a nuclear-targeted material MeTPAE with aggregation-induced emission (AIE) characteristics was developed based on a triphenylamine structure skeleton. MeTPAE can not only interact with histone deacetylases (HDACs) to inhibit cell proliferation but also damage telomere and nucleic acids precisely through photodynamic treatment (PDT). The cocktail strategy of MeTPAE caused obvious cell cycle arrest and showed excellent PDT anti-tumor activity, which offered new opportunities for the effective treatment of malignant tumors.

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Histone deacetylase (HDAC) inhibitors in cancer: a patent review (2017-present)

Cited by 101 publications

References 59 publications

Structure-Based Inhibitor Discovery of Class I Histone Deacetylases (HDACs)

Structure-Based Inhibitor Discovery of Class I Histone Deacetylases (HDACs)

Natural Products Extracted from Fungal Species as New Potential Anti-Cancer Drugs: A Structure-Based Drug Repurposing Approach Targeting HDAC7

A Nuclear‐Targeted AIE Photosensitizer for Enzyme Inhibition and Photosensitization in Cancer Cell Ablation

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