Peretinoin, an Acyclic Retinoid, for the Secondary Prevention of Hepatocellular Carcinoma

Woo, Hyun Young; Yoo, So Young; Heo, Jeong

doi:10.3390/molecules26020295

Cited by 7 publications

(4 citation statements)

References 54 publications

(79 reference statements)

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“…Recently, researchers reported that sulfarotene (WYC-209), an acyclic retinoid, overcame HCC resistance in a subset of cancer cells that were responsible for drug resistance (i.e., tumor-repopulating cells), possibly via RARα [ 217 ]. A promising retinoid at present for the prevention of HCC recurrence is peretinoin (NIK-333) [ 218 , 219 ], which is in clinical trials that are discussed in a separate review [ 220 ]. Pre-clinical studies showed that peretinoin suppressed steatosis and tumorigenesis in a mouse model of diet-induced NASH and HCC by promoting autophagy and inhibiting pro-inflammatory pathways [ 221 ].…”

Section: Retinoids In Liver Cancermentioning

confidence: 99%

Retinoids in the Pathogenesis and Treatment of Liver Diseases

et al. 2022

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Vitamin A (VA), all-trans-retinol (ROL), and its analogs are collectively called retinoids. Acting through the retinoic acid receptors RARα, RARβ, and RARγ, all-trans-retinoic acid, an active metabolite of VA, is a potent regulator of numerous biological pathways, including embryonic and somatic cellular differentiation, immune functions, and energy metabolism. The liver is the primary organ for retinoid storage and metabolism in humans. For reasons that remain incompletely understood, a body of evidence shows that reductions in liver retinoids, aberrant retinoid metabolism, and reductions in RAR signaling are implicated in numerous diseases of the liver, including hepatocellular carcinoma, non-alcohol-associated fatty liver diseases, and alcohol-associated liver diseases. Conversely, restoration of retinoid signaling, pharmacological treatments with natural and synthetic retinoids, and newer agonists for specific RARs show promising benefits for treatment of a number of these liver diseases. Here we provide a comprehensive review of the literature demonstrating a role for retinoids in limiting the pathogenesis of these diseases and in the treatment of liver diseases.

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Section: Retinoids In Liver Cancermentioning

confidence: 99%

Retinoids in the Pathogenesis and Treatment of Liver Diseases

et al. 2022

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“…Since the structure of compound 5 possesses both an indole and retinoid group, understanding the biological activities of these substituents is also important. ATRA and its derivatives have been used to suppress the proliferation of various types of cancers [32][33][34] especially AML [35]. The effects of ATRA on acute promyelocytic leukemia, a type of acute myeloid leukemia, are mainly due to the induction cell differentiation [36].…”

Section: Discussionmentioning

confidence: 99%

Novel indole retinoid derivative induces apoptosis and cell cycle arrest and modulates AKT and ERK signaling in HL‐60 cells

Gurkan‐Alp

Karabay

Koç

et al. 2023

Fundamemntal Clinical Pharma

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Chemotherapy with targeted drugs is the first line therapy option for acute and chronic myeloid leukemia. However, hematopoietic stem cell transplantation may be used in high-risk patients or patients with failed responses to chemo drugs. Discovery and development of more effective new agents with lower side effects is the main aim of leukemia treatment. In this study, a novel retinoid compound with tetrahydronaphthalene ring was synthesized and evaluated for anticancer activity in human chronic and acute myeloid leukemia cell lines K562 and HL-60. Novel N-(1H-indol-1-yl)-5,-5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene-2-carboxamide was synthesized based on molecular hybridization of the two different bioactive structures retinoid head and indole. The effects of the synthesized carboxamide compound, which was referred to as compound 5, were determined in K562 chronic myeloid leukemia and HL-60 acute myeloid leukemia cell lines and L929 fibroblast cell line, which served as a control. Colorimetric MTT and caspase3 activity tests, flow cytometry, western blot, and microscopic examinations were used to evaluate biological activity. Compound 5 more effectively induced cell death in HL60 cells in comparison to K562 cells and L929 fibroblast cells. Therefore, further mechanism of cell death was investigated in HL60 cell line. It was found that compound 5 induced remarkable cytotoxicity, caspase3 activation, and PARP fragmentation in HL60 cells. Flow cytometric staining showed that the percentage of cells arrested in G0/G1 was also increased with compound 5 treatment. Important modulator proteins of cell proliferation p-ERK, p-AKT, and p-m-TOR were also found to be inhibited with compound 5 treatment. Collectively, our results reveal compound 5, which is a novel indole retinoid compound as a potential active agent for the treatment of acute promyelocytic leukemia.

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“…In addition, terpenoids II (Scheme 1a-1), dimers of the related retinal and their analogues, are a large family of naturally occurring pigments and are related to numerous physiological functions, and many of them are also fundamental chemicals widely applied in food, nutrition, cosmetics, and elsewhere. [4,9] Inspired by the functions of these natural compounds, many non-natural bioactive molecules I, such as peretinoin (NIK-333; phase III trials), [10] ALRT1550, [11] acitretin, [4] and fenretinide, [12] have been invented (Scheme 1a-2).…”

Section: Introductionmentioning

confidence: 99%

A Modular Approach for the Synthesis of Natural and Artificial Terpenoids

Wang

Huang

et al. 2023

Angew Chem Int Ed

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Many terpenoids with isoprene unit(s) demonstrating critical biological activities have been isolated and characterized. In this study, we have developed a robust chem‐stamp strategy for the construction of the key isoprene unit, which consists of two steps: one‐carbon extension of aldehydes to the alkenyl boronates by the boron‐Wittig reaction and the rhodium‐catalyzed reaction of alkenyl boronates with 2,3‐allenols to yield enals. This chem‐stamp could readily be applied repeatedly and separately, enabling the modular concise synthesis of many natural and pharmaceutically active terpenoids, including retinal, β‐carotene, vitamin A, tretinoin, fenretinide, acitretin, ALRT1550, nigerapyrone C, peretinoin, and lycopene. Owing to the diversified availability of the starting materials, aldehydes and 2,3‐allenols, creation of new non‐natural terpenoids has been realized from four dimensions: the number of isoprene units, the side chain, and the two terminal groups.

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Peretinoin, an Acyclic Retinoid, for the Secondary Prevention of Hepatocellular Carcinoma

Cited by 7 publications

References 54 publications

Retinoids in the Pathogenesis and Treatment of Liver Diseases

Retinoids in the Pathogenesis and Treatment of Liver Diseases

Novel indole retinoid derivative induces apoptosis and cell cycle arrest and modulates AKT and ERK signaling in HL‐60 cells

A Modular Approach for the Synthesis of Natural and Artificial Terpenoids

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