College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea.
College of Pharmacy, Kyungsung University, Busan 48434, Republic of Korea.
Bioorg Med Chem Lett. 2019 Jan 1;29(1):62-65. doi: 10.1016/j.bmcl.2018.11.010. Epub 2018 Nov 8.
Triple-negative breast cancers (TNBCs) are characterized as an invasive and intractable subtype of breast cancers. Overexpression of epidermal growth factor receptor (EGFR) has been considered to be an important target for TNBC therapy, but efficacies of EGFR inhibitors in clinical trials are elusive. In this study, novel series of 2-anilinopyrimidines were synthesized in an effort to identify selective inhibitors against an EGFR-overexpressing TNBC cell line. Biological evaluation demonstrated that compounds 21 and 38, with a 4-methylpiperidine group and a high ClogP value, exhibited good potency and selectivity for the TNBC cell line. This study has provided evidence to support further development of 2-anilinopyrimidine-based TNBC selective inhibitors and investigation of the targets of compounds 21 and 38.
三阴性乳腺癌（TNBCs）是一种侵袭性和难治性的乳腺癌亚型。表皮生长因子受体（EGFR）的过表达被认为是 TNBC 治疗的一个重要靶点，但 EGFR 抑制剂在临床试验中的疗效却难以捉摸。在这项研究中，我们合成了一系列新型 2-苯胺嘧啶，旨在寻找针对 EGFR 过表达的 TNBC 细胞系的选择性抑制剂。生物学评价表明，具有 4-甲基哌啶基和高 ClogP 值的化合物 21 和 38 对 TNBC 细胞系具有良好的活性和选择性。这项研究为进一步开发基于 2-苯胺嘧啶的 TNBC 选择性抑制剂以及研究化合物 21 和 38 的靶点提供了依据。
