Caspase inhibitors: a review of recently patented compounds (2013-2015)

Lee, Hyemin; Shin, Eun Ah; Ahn, Deoksoo; Kim, Chang Geun; Kim, Ju‐Ha; Kim, Sung Hoon

doi:10.1080/13543776.2017.1378426

Cited by 46 publications

(34 citation statements)

References 115 publications

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“…Even many caspase inhibitors (e.g., inhibitors of caspase-1, capses-2, caspase-6, and caspase-3) have been patented for their use in the treatments of neurodegenerative diseases, cardiovascular diseases, liver diseases, and cerebral stroke. To date, however, no caspase inhibitors have entered the market due to their toxicity and poor pharmacokinetic profile [122].…”

Section: Caspase Inhibitorsmentioning

confidence: 99%

Presbycusis: An Update on Cochlear Mechanisms and Therapies

Wang

Puel

2020

JCM

150

125

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Age-related hearing impairment (ARHI), also referred to as presbycusis, is the most common sensory impairment seen in the elderly. As our cochlea, the peripheral organ of hearing, ages, we tend to experience a decline in hearing and are at greater risk of cochlear sensory-neural cell degeneration and exacerbated age-related hearing impairments, e.g., gradual hearing loss, deterioration in speech comprehension (especially in noisy environments), difficulty in the localization sound sources, and ringing sensations in the ears. However, the aging process does not affect people uniformly; nor, in fact, does the aging process appear to be uniform even within an individual. Here, we outline recent research into chronological cochlear age in healthy people, and exacerbated hearing impairments during aging due to both extrinsic factors including noise and ototoxic medication, and intrinsic factors such as genetic predisposition, epigenetic factors, and aging. We review our current understanding of molecular pathways mediating ARHL and discuss recent discoveries in experimental hearing restoration and future prospects.

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Section: Caspase Inhibitorsmentioning

confidence: 99%

Presbycusis: An Update on Cochlear Mechanisms and Therapies

Wang

Puel

2020

JCM

150

125

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“…In mouse studies, infusing an anticaspase-2 morpholino into mouse brain reduced caspase-2 protein levels and its cleavage of tau to reverse memory deficits without adverse effects [24]. To the best of our knowledge, there are currently no caspase-2 selective inhibitors available although a patent has been filed for nasal administration of a peptide inhibitor, with the amino acid sequence AFDAFC, targeting caspase-2 for treatment of neurodegenerative disorders such as ALS, Creutzfeldt-Jacob disease, AD, MCI, PD and HD [6].…”

Section: Therapeutic Targeting Of Caspases In Metabolic Diseasementioning

confidence: 99%

“…However, the precise function of specific caspases is still unclear, and evidence of cross-talk between alternative cell death pathways may complicate therapeutic blocking of apoptosis to treat metabolic diseases. Due to high overlap in substrate selectivity among caspase family members, there is currently a lack of available specific small-molecule inhibitors, although a number of compounds have been patented [6,7]. Therefore, novel targeting strategies involving nanoparticle siRNA delivery or future utilisation of CRISPR-Cas9 gene-editing approaches may be required to therapeutically ablate individual caspases.…”

Section: Introductionmentioning

confidence: 99%

Caspases in metabolic disease and their therapeutic potential

Wilson

Kumar

2018

Cell Death Differ

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Caspases, a family of cysteine-dependent aspartate-specific proteases, are central to the maintenance of cellular and organismal homoeostasis by functioning as key mediators of the inflammatory response and/or apoptosis. Both metabolic inflammation and apoptosis play a central role in the pathogenesis of metabolic disease such as obesity and the progression of nonalcoholic steatohepatisis (NASH) to more severe liver disease. Obesity and nonalcoholic fatty liver disease (NAFLD) are the leading global health challenges associated with the development of numerous comorbidities including insulin resistance, type-2 diabetes and early mortality. Despite the high prevalence, current treatment strategies including lifestyle, dietary, pharmaceutical and surgical interventions, are often limited in their efficacy to manage or treat obesity, and there are currently no clinical therapies for NAFLD/NASH. As mediators of inflammation and cell death, caspases are attractive therapeutic targets for the treatment of these metabolic diseases. As such, pan-caspase inhibitors that act by blocking apoptosis have reached phase I/II clinical trials in severe liver disease. However, there is still a lack of knowledge of the specific and differential functions of individual caspases. In addition, cross-talk between alternate cell death pathways is a growing concern for long-term caspase inhibition. Evidence is emerging of the important cell-death-independent, non-apoptotic functions of caspases in metabolic homoeostasis that may be of therapeutic value. Here, we review the current evidence for roles of caspases in metabolic disease and discuss their potential targeting as a therapeutic strategy.

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“…Extracellular vesicles are released by hepatocytes after lipid treatment and caspase‐3 seems to be necessary as well as the activation of Rho‐associated coiled‐coil‐containing protein kinase 1 . Based on such findings, caspase‐3 may constitute a target for the treatment of NASH and various caspase inhibitors are evaluated for their effects However, pharmacological caspase inhibition may be hazardous as it can switch hepatocytes apoptosis to other forms of cell death …”

Section: Extracellular Vesicles In Chronic Liver Diseasesmentioning

confidence: 99%

Extracellular vesicles: Future diagnostic and therapeutic tools for liver disease and regeneration

Balaphas

Meyer

Sadoul

et al. 2019

Liver International

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Extracellular vesicles are membrane fragments that can be produced by all cell types. Interactions between extracellular vesicles and various liver cells constitute an emerging field in hepatology and recent evidences have established a role for extracellular vesicles in various liver diseases and physiological processes. Extracellular vesicles originating from liver cells are implicated in intercellular communication and fluctuations of specific circulating extracellular vesicles could constitute new diagnostic tools. In contrast, extracellular vesicles derived from progenitor cells interact with hepatocytes or non‐parenchymal cells, thereby protecting the liver from various injuries and promoting liver regeneration. Our review focuses on recent developments investigating the role of various types of extracellular vesicles in acute and chronic liver diseases as well as their potential use as biomarkers and therapeutic tools.

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Caspase inhibitors: a review of recently patented compounds (2013-2015)

Cited by 46 publications

References 115 publications

Presbycusis: An Update on Cochlear Mechanisms and Therapies

Presbycusis: An Update on Cochlear Mechanisms and Therapies

Caspases in metabolic disease and their therapeutic potential

Extracellular vesicles: Future diagnostic and therapeutic tools for liver disease and regeneration

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