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- Son, Seohyun;
- Elkamhawy, Ahmed;
- Gul, Anam Rana;
- Al-Karmalawy, Ahmed A.;
- Alnajjar, Radwan;
- ... Choi, Won Jun;
- ... Lee, Kyeong;
- 외 5명
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10SCOPUS
10초록
Epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) protein tyrosine kinases co-expressed in various cancers such as ovarian, breast, colon, and prostate subtypes. Herein, new TAK-285 derivatives (9a-h) were synthesised, characterised, and biologically evaluated as dual EGFR/HER2 inhibitors. Compound 9f exhibited IC50 values of 2.3 nM over EGFR and 234 nM over HER2, which is 38-fold of staurosporine and 10-fold of TAK-285 over EGFR. Compound 9f also showed high selectivity profile when tested over a small kinase panel. Compounds 9a-h showed IC50 values in the range of 1.0-7.3 nM and 0.8-2.8 nM against PC3 and 22RV1 prostate carcinoma cell lines, respectively. Cell cycle analysis, apoptotic induction, molecular docking, dynamics, and MM-GBSA studies confirmed the plausible mechanism(s) of compound 9f as a potent EGFR/HER2 dual inhibitor with an effective antiproliferative action against prostate carcinoma.
키워드
- 제목
- Development of new TAK-285 derivatives as potent EGFR/HER2 inhibitors possessing antiproliferative effects against 22RV1 and PC3 prostate carcinoma cell lines
- 저자
- Son, Seohyun; Elkamhawy, Ahmed; Gul, Anam Rana; Al-Karmalawy, Ahmed A.; Alnajjar, Radwan; Abdeen, Ahmed; Ibrahim, Samah F.; Alshammari, Saud O.; Alshammari, Qamar A.; Choi, Won Jun; Park, Tae Jung; Lee, Kyeong
- 발행일
- 2023-12
- 유형
- Article
- 권
- 38
- 호
- 1
- 페이지
- 1 ~ 17