論文 - 詳細
| RRC ID | 72195 |
|---|---|
| 著者 | Ciftci HI, Radwan MO, Sever B, Hamdy AK, Emirdağ S, Ulusoy NG, Sozer E, Can M, Yayli N, Araki N, Tateishi H, Otsuka M, Fujita M, Altintop MD. |
| タイトル | EGFR-Targeted Pentacyclic Triterpene Analogues for Glioma Therapy. |
| ジャーナル | Int J Mol Sci |
| Abstract |
Glioma, particularly its most malignant form, glioblastoma multiforme (GBM), is the most common and aggressive malignant central nervous system tumor. The drawbacks of the current chemotherapy for GBM have aroused curiosity in the search for targeted therapies. Aberrantly overexpressed epidermal growth factor receptor (EGFR) in GBM results in poor prognosis, low survival rates, poor responses to therapy and recurrence, and therefore EGFR-targeted therapy stands out as a promising approach for the treatment of gliomas. In this context, a series of pentacyclic triterpene analogues were subjected to in vitro and in silico assays, which were conducted to assess their potency as EGFR-targeted anti-glioma agents. In particular, compound 10 was the most potent anti-glioma agent with an IC50 value of 5.82 µM towards U251 human glioblastoma cells. Taking into account its low cytotoxicity to peripheral blood mononuclear cells (PBMCs), compound 10 exerts selective antitumor action towards Jurkat human leukemic T-cells. This compound also induced apoptosis and inhibited EGFR with an IC50 value of 9.43 µM compared to erlotinib (IC50 = 0.06 µM). Based on in vitro and in silico data, compound 10 stands out as a potential orally bioavailable EGFR-targeted anti-glioma agent endowed with the ability to cross the blood-brain barrier (BBB). |
| 巻・号 | 22(20) |
| 公開日 | 2021-10-11 |
| DOI | 10.3390/ijms222010945 |
| PII | ijms222010945 |
| PMID | 34681605 |
| PMC | PMC8537327 |
| MeSH | Apoptosis / drug effects Binding Sites Brain Neoplasms / metabolism Brain Neoplasms / pathology Cell Line, Tumor Cell Survival / drug effects Drug Screening Assays, Antitumor ErbB Receptors / antagonists & inhibitors ErbB Receptors / metabolism Glioma / metabolism Glioma / pathology Half-Life Humans Leukocytes, Mononuclear / cytology Leukocytes, Mononuclear / drug effects Leukocytes, Mononuclear / metabolism Molecular Docking Simulation Pentacyclic Triterpenes / chemistry* Pentacyclic Triterpenes / metabolism Pentacyclic Triterpenes / pharmacology |
| IF | 4.556 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 4 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | U251(RCB0461) |