83889-95-6Relevant articles and documents
Conjugates Derived from Lapatinib Derivatives with Cancer Cell Stemness Inhibitors Effectively Reversed Drug Resistance in Triple-Negative Breast Cancer
Wang, Yuanjiang,Lv, Zhaodan,Chen, Feihong,Wang, Xing,Gou, Shaohua
supporting information, p. 12877 - 12892 (2021/09/13)
Increasing evidence indicates that the cancer stem cell (CSC) subpopulation contributes to the therapeutic resistance and metastasis of tumors, leading to patient recurrence and death. Herein, we designed and synthesized several compounds by conjugating lapatinib derivatives with different CSC inhibitors to treat with lapatinib-induced MDA-MB-231 drug-resistant cells. In vitro biological studies indicated that 3a showed strong cytotoxicity and EGFR enzyme inhibitory activity and effectively reversed lapatinib-mediated resistance of MDA-MB-231 cells via inhibiting triple-negative breast cancer (TNBC) cell stemness and the AKT/ERK signaling pathway. In addition, 3a was capable of strongly suppressing the invasion and migration of TNBC cells by inhibiting the Wnt/β-catenin signaling pathway and MMP-2 and MMP-9 protein expression. In vivo tumorigenicity tests showed that 3a could inhibit the occurrence of TNBC by inhibiting BCSCs, proving 3a is a potential EGFR and CSC dual inhibitor for TNBC treatment.
Novel small molecule compound, preparation method and application thereof in preparation of mycobacterium drugs for resisting drug-resistant mycobacterium tuberculosis and like
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Paragraph 0015; 0021-0022, (2019/08/12)
The invention discloses a novel small molecule compound and a preparation method and application thereof in preparation of mycobacterium drugs for resisting drug-resistant mycobacterium tuberculosis and like. The novel mycobacterium-resistant small molecule has a structural general formula (I), and the small molecule compound disclosed by the invention has a relatively good inhibition effect on mycobacteria. The antibacterial activity of mycobacterium smegmatis, mycobacterium tuberculosis H37Rv, H37Ra and drug-resistant mycobacterium tuberculosis are determined, and results show that the smallmolecule compound has good antibacterial activity on mycobacterium smegmatis, mycobacterium tuberculosis H37Rv, H37Ra and drug-resistant mycobacterium tuberculosis, and has an application prospect inpreparation of mycobacterium tuberculosis-resistant drugs.
Design, synthesis and activity of BBI608 derivatives targeting on stem cells
Zhou, Qifan,Peng, Chen,Du, Fangyu,Zhou, Linbo,Shi, Yajie,Du, Yang,Liu, Dongdong,Sun, Wenjiao,Zhang, Meixia,Chen, Guoliang
, p. 39 - 50 (2018/04/02)
STAT3 plays a vital role in maintaining the self-renewal of tumor stem cells. BBI608, a small molecule identified by its ability to inhibit gene transcription driven by STAT3 and cancer stemness properties, can inhibit stemness gene expression and kill stemness-high cancer cells isolated from a variety of cancer types. In order to improve the pharmacokinetic properties of BBI608 and the antitumor activity, a series of BBI608 derivatives were designed and synthesized here. Most of these compounds were more potent than BBI608 on HepG2 cells, compound LD-8 had the most potent inhibitory activity among them and was 5.4-fold more potent than BBI608 (IC50 = 11.2 μM), but had considerable activity on normal liver cells L-02. Compounds LD-17 (IC50 = 3.5 μM) and LD-19 (IC50 = 2.9 μM) were found to possess significant inhibitory activities and good selectivity. The results showed that compound LD-19 was worthy to investigate further as a lead compound according to its potent inhibitory activity, ideal ClogP value and better water solubility.