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| Type |
Poster Presentation |
| Area |
Medicinal Chemistry |
| Room No. |
Exhibition Hall 2+3 |
| Time |
10월 19일 (목요일) 11:00~12:30 |
| Code |
MEDI.P-323 |
| Subject |
EGFR Allosteric Inhibitors for Lung Cancer |
| Authors |
SEO YOUNG LEE, Gildon Choi1, Chong Hak Chae2, Inji Shin3, Kwangho Lee2,*
Medicinal Chemistry, University of Science and Technology(KRICT), Korea
1Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology, Korea
2Korea Research Institute of Chemical Technology, Korea
3Center for Medicinal Chemistry, Korea Research Institute of Chemical Technology, Korea
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| Abstract |
Erlotinib (Tarceva) & Gefitinib (Iressa) are currently in clinic use as epidermal growth factor receptor (EGFR) kinase inhibitors for non-small-cell lung cancer (NSCLC). However, their clinical efficacy is limited by both their mechanism-based toxicity and the development of drug-resistance mutations, including the gatekeeper T790M mutation.
Afatinib, a quinazoline-based irreversible pan-EGFR inhibitor dubbed as second generation EGFR TKI, is limited in wide clinical use due to unwanted adverse effect such as severe rash and diarrhea.
Osimertinib is a pyrimidine-based irreversible third generation EGFR-TKI and features selective EGFR T790M inhibition while sparing wild-type EGFR activity. However, during osimertinib clinical study, various acquired resistances were reported. In particular, polar nucleophilic cysteine mutation into polar non-nucleophilic serine at EGFR 797 position was detected in resistant patients. To address newly identified EGFR T790M/C797S mutants, new strategic approach is attempted. Unlike conventional catalytic site inhibitors, allosteric site inhibitors may provide novel inhibitors for EGFR T790M/C797S mutants and bring different mutational profiles for combination therapy with current EGFR-TKIs.
In this presentation, strategy for EGFR allosteric inhibitors and current research progress will be discussed.
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| E-mail |
se2k@naver.com |
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120th General Meeting of the KCS