Article
Design, Synthesis, and Biological Activity of Marinacarboline Analogues as STAT3 Pathway Inhibitors for Docetaxel-Resistant Triple-Negative Breast CancerClick to copy article linkArticle link copied!
- Woong Sub ByunWoong Sub ByunResearch Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Republic of KoreaNatural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 08826, Republic of KoreaMore by Woong Sub Byun
- Hyewon LimHyewon LimResearch Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Republic of KoreaMore by Hyewon Lim
- Junhwa HongJunhwa HongResearch Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Republic of KoreaMore by Junhwa Hong
- Eun Seo BaeEun Seo BaeNatural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 08826, Republic of KoreaMore by Eun Seo Bae
- Seok Beom LeeSeok Beom LeeResearch Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Republic of KoreaMore by Seok Beom Lee
- Younggwan KimYounggwan KimResearch Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Republic of KoreaMore by Younggwan Kim
- Jeeyeon LeeJeeyeon LeeResearch Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Republic of KoreaMore by Jeeyeon Lee
- Sang Kook Lee*Sang Kook Lee*Email: [email protected]Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 08826, Republic of KoreaMore by Sang Kook Lee
- Suckchang Hong*Suckchang Hong*Email: [email protected]Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Republic of KoreaMore by Suckchang Hong
Abstract
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Metastatic triple-negative breast cancer (mTNBC) is a fatal type of breast cancer (BC), and signal transducer and activator of transcription 3 (STAT3) has emerged as an effective target for mTNBC. In the present study, compound MC0704 was found to be a novel synthetic STAT3 pathway inhibitor, and its potential antitumor activity was demonstrated using in vitro and in vivo models in docetaxel-resistant TNBC cells. Based on marinacarboline (MC), a series β-carboline derivatives were synthesized and investigated for their antitumor activities against docetaxel-resistant MDA-MB-231 (MDA-MB-231-DTR) cells. Combining antiproliferation and STAT3 inhibitory activities, MC0704 was selected as the most promising β-carboline compound. MC0704 effectively impeded the metastatic potential of MDA-MB-231-DTR cells in vitro, and the combination of MC0704 and docetaxel exhibited potent antitumor activities in a xenograft mouse model. These findings suggested that MC0704 can be a lead candidate as a target therapeutic agent for TNBC patients with docetaxel resistance.
Copyright © 2023 American Chemical Society
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