2. Academic Validation
  3. Bipyridine Derivatives as NOP2/Sun RNA Methyltransferase 3 Inhibitors for the Treatment of Colorectal Cancer

Bipyridine Derivatives as NOP2/Sun RNA Methyltransferase 3 Inhibitors for the Treatment of Colorectal Cancer

  • J Med Chem. 2024 Aug 8;67(15):13446-13473. doi: 10.1021/acs.jmedchem.4c01323.
Zhen Tang 1,  Ningjing Zhang 1,  Shuang Chen 1,  Jiebin Fang 1,  Xinyi Tang 1,  Yijie Lou 2,  Yongjun Jiang 3,  Yijun Ma 1,  Xiaoming Chen 1,  Zhe Chen 2,  Shuai Zhan 1,  Xia Ding 1,  Wanjing Ding 1 4,  Zhongjun Ma 1 4
Affiliations

Affiliations

  • 1 Institute of Marine Biology and Pharmacology, Ocean College, Zhejiang University, Zhoushan 316021, China.
  • 2 Key Laboratory of Digestive Pathophysiology of Zhejiang Province, the First Affiliated Hospital of Zhejiang Chinese Medicine, First Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou 310053, China.
  • 3 College of Food and Pharmacy, Zhejiang Ocean University, Zhoushan 316021, China.
  • 4 Hainan Institute of Zhejiang University, Sanya 572025, China.
PMID: 39054645 DOI: 10.1021/acs.jmedchem.4c01323
Abstract

Based on the structure of caerulomycin A, 90 novel bipyridine derivatives were designed and synthesized. Among these, compound B19 exerted strong antitumor effects in vivo and in vitro. Importantly, NOP2/Sun RNA methyltransferase 3 (NSUN3) protein was identified as the target specific binding to B19, which inhibits Oxidative Phosphorylation of mitochondrial energy metabolism and enhances glycolytic activity by binding to NSUN3. Knockdown of NSUN3 inhibited both proliferation and migration of colorectal Cancer (CRC) cells by activating AMPK-related signaling and inhibiting downstream STAT3 signaling to exert antiproliferative and pro-apoptotic effects. Our findings support the use of NSUN3 inhibitors as promising therapeutic strategies against CRC.

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