| Project/Area Number |
26293028
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Drug development chemistry
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| Research Institution | Nagasaki University |
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Principal Investigator |
IWAO Masatomo 長崎大学, 工学研究科, 教授 (00100892)
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| Co-Investigator(Kenkyū-buntansha) |
石橋 郁人 長崎大学, 水産・環境科学総合研究科(水産), 教授 (10192486)
福田 勉 長崎大学, 工学研究科, 助教 (80295097)
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| Co-Investigator(Renkei-kenkyūsha) |
UNNO Hideaki 長崎大学, 工学研究科, 助教 (10452872)
UEHARA Yoshimasa 岩手医科大学, 薬学部, 教授 (50160213)
NISHIYA Naoyuki 岩手医科大学, 薬学部, 講師 (10286867)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2016: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2015: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2014: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
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| Keywords | 非小細胞肺がん / EGFR-TKI / L858R/T790M変異 / L858R/T790M/C797S変異 / ゲフィチニブ耐性 / オシメルチニブ耐性 / ラメラリン / アザラメラリン / L858R/T790M / L858R/T790M/C797S / ゲフィチニブ / オシメルチニブ / アザアメラリン / 薬剤耐性変異 / アファチニブ |
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| Outline of Final Research Achievements |
A new class of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) effective against the drug-resistant EGFR mutants has been developed via structural modification of the marine natural product lamellarin N and its lactam congener azalamellain N. Thus, the designed analogues possessing water-solubilizing aminoalkyl group(s) at the A-ring of their pentacyclic lamellarin core exhibited potent inhibitory activity against the gefitinib-resistant EGFR(L858R/T790M) double mutant in enzyme assay. Moreover, these compounds effectively suppressed proliferation of Ba/F3 cells, which were transduced with the osimertinib-resistant EGFR(L858R/T790M/C797S) triple mutant, in EGFR-dependent manner.
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