Discovery of Potent Antiproliferative Agents Targeting EGFR Tyrosine Kinase Based on the Pyrido[3',2':4,5]thieno[3,2-d]pyrimidin-4-amine Scaffold
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- Aziz Yasmine Mohamed Abdel
- Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Suez Canal University
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- Said Mohamed Mokhtar
- Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Suez Canal University
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- El Shihawy Hosam Ahmed
- Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Suez Canal University
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- Tolba Mai Fathy
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University
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- Abouzid Khaled Abouzid Mohamed
- Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ain Shams University
書誌事項
- タイトル別名
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- Discovery of Potent Antiproliferative Agents Targeting EGFR Tyrosine Kinase Based on the Pyrido[3′,2′:4,5]thieno[3,2-<i>d</i>]pyrimidin-4-amine Scaffold
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A series of pyridothieno[3,2-d]pyrimidin-4-amines was designed and synthesized as congeners to the classical 4-anilinoquinazolines as ATP-competitive epidermal growth factor receptor (EGFR) inhibitors. Compound 5a exhibited the most potent and selective inhibitory activity against EGFR with an IC50 value of 36.7 nM. Moreover, compounds 4b and 5a showed remarkable cell growth inhibition against leukemia, central nervous system cancer, and non-small cell lung cancer cell lines that overexpress EGFR, with growth inhibition of 50% (GI50) values of around 10 nM in the full U.S. National Cancer Institute 60 cell panel assay. Cell cycle studies indicated that compounds 4b and 5a induced significant cell cycle arrest in the S-phase and G0/G1, respectively, in addition to boosting P27kip expression. Compound 5a did not alter the viability of placental trophoblasts, which reflects its safety for normal cells. The standard COMPARE analyses demonstrated considerable correlation levels between compounds 4b and 5a and erlotinib, with pyridinium chlorochromate (PCC) values of 0.707 and 0.727, respectively.
収録刊行物
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- CHEMICAL & PHARMACEUTICAL BULLETIN
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CHEMICAL & PHARMACEUTICAL BULLETIN 63 (12), 1015-1028, 2015
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390001204178702592
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- NII論文ID
- 130005112207
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- NII書誌ID
- AA00602100
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- ISSN
- 13475223
- 00092363
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- NDL書誌ID
- 026949978
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- PubMed
- 26633023
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可