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- W3048237053 abstract ": Diffuse intrinsic pontine glioma (DIPG) mainly affects children with a median age of 6-7 years old. It accounts for 10% of all pediatric tumors. Unfortunately, DIPG has a poor prognosis, and the median survival is generally less than 16-24 months independently from the treatment received. Up to now, children with DIPG are treated with focal radiotherapy alone or in combination with antitumor agents. : In the last decade, ONC201 known as dopamine receptor antagonist was uncovered, by a high throughput screening of public libraries of compounds, to be endowed with cytotoxic activity against several cancer cell lines. Efforts were made to identify the real ONC201 target, responsible for its antiproliferative effect. The hypothesized targets were the Tumor necrosis factor-Related Apoptosis-Inducing Ligand stimulation (TRAIL), two oncogenic kinases (ERK/AKT system) that target the same tumor-suppressor gene (FOXO3a), dopamine receptors (DRD2 and DRD3 subtypes) and finally the mitochondrial Caseynolitic Protease P (ClpP). ONC201 structure-activity relationship is extensively discussed in this review, together with other two classes of compounds, namely ADEPs and D9, already known for their antibiotic activity but noteworthy to be discussed and studied as potential “leads” for the development of new drugs to be used in the treatment of DIPG. : In this review, a detailed and critical description of ONC201, ADEPs, and D9 pro-apoptotic activity is made, with particular attention to the specific interactions established with its targets that also are intimately described. Pubmed published patents and clinical trial reports of the last ten years were used as the bibliographic source." @default.
- W3048237053 created "2020-08-13" @default.
- W3048237053 creator A5012291954 @default.
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- W3048237053 creator A5028271488 @default.
- W3048237053 creator A5050985208 @default.
- W3048237053 creator A5054163069 @default.
- W3048237053 date "2021-05-01" @default.
- W3048237053 modified "2023-10-10" @default.
- W3048237053 title "Diffuse Intrinsic Pontine Glioma (DIPG): Breakthrough and Clinical Perspective" @default.
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