1. Academic Validation
  2. Chemical inhibition of prometastatic lysyl-tRNA synthetase-laminin receptor interaction

Chemical inhibition of prometastatic lysyl-tRNA synthetase-laminin receptor interaction

  • Nat Chem Biol. 2014 Jan;10(1):29-34. doi: 10.1038/nchembio.1381.
Dae Gyu Kim 1 Jin Young Lee 1 Nam Hoon Kwon 2 Pengfei Fang 3 Qian Zhang 4 Jing Wang 3 Nicolas L Young 5 Min Guo 3 Hye Young Cho 6 Ameeq Ul Mushtaq 6 Young Ho Jeon 6 Jin Woo Choi 7 Jung Min Han 2 Ho Woong Kang 8 Jae Eun Joo 8 Youn Hur 8 Wonyoung Kang 9 Heekyoung Yang 9 Do-Hyun Nam 9 Mi-Sook Lee 10 Jung Weon Lee 10 Eun-Sook Kim 11 Aree Moon 11 Kibom Kim 2 Doyeun Kim 2 Eun Joo Kang 12 Youngji Moon 12 Kyung Hee Rhee 10 Byung Woo Han 10 Jee Sun Yang 13 Gyoonhee Han 13 Won Suk Yang 2 Cheolju Lee 14 Ming-Wei Wang 15 Sunghoon Kim 16
Affiliations

Affiliations

  • 1 1] Medicinal Bioconvergence Research Center, Seoul National University, Seoul, Korea. [2] Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Korea. [3].
  • 2 1] Medicinal Bioconvergence Research Center, Seoul National University, Seoul, Korea. [2] Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Korea.
  • 3 Department of Cancer Biology, The Scripps Research Institute, Scripps Florida, Jupiter, Florida, USA.
  • 4 Department of Chemistry and Biochemistry, Florida State University, Tallahassee, Florida, USA.
  • 5 Ion Cyclotron Resonance Program, National High Magnetic Field Laboratory, Florida State University, Tallahassee, Florida, USA.
  • 6 College of Pharmacy, Korea University, Sejong, Korea.
  • 7 1] Medicinal Bioconvergence Research Center, Seoul National University, Seoul, Korea. [2] Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
  • 8 Yuhan Research Institute, Yongin, Korea.
  • 9 Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
  • 10 Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Korea.
  • 11 College of Pharmacy, Duksung Women's University, Seoul, Korea.
  • 12 Medicinal Bioconvergence Research Center, Seoul National University, Seoul, Korea.
  • 13 Translational Research Center for Protein Function Control, Department of Biotechnology and WCU Department of Biomedical Sciences, Yonsei University, Seoul, Korea.
  • 14 BRI, Korea Institute of Science and Technology, Seoul, Korea.
  • 15 The National Center for Drug Screening, Zhangjiang High-Tech Park, Shanghai, China.
  • 16 1] Medicinal Bioconvergence Research Center, Seoul National University, Seoul, Korea. [2] Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Korea. [3] World Class University Department of Molecular Medicine and Biopharmaceutical Sciences, Seoul National University, Seoul, Korea.
Abstract

Lysyl-tRNA synthetase (KRS), a protein synthesis Enzyme in the cytosol, relocates to the plasma membrane after a laminin signal and stabilizes a 67-kDa laminin receptor (67LR) that is implicated in Cancer metastasis; however, its potential as an antimetastatic therapeutic target has not been explored. We found that the small compound BC-K-YH16899, which binds KRS, impinged on the interaction of KRS with 67LR and suppressed metastasis in three different mouse models. The compound inhibited the KRS-67LR interaction in two ways. First, it directly blocked the association between KRS and 67LR. Second, it suppressed the dynamic movement of the N-terminal extension of KRS and reduced membrane localization of KRS. However, it did not affect the catalytic activity of KRS. Our results suggest that specific modulation of a cancer-related KRS-67LR interaction may offer a way to control metastasis while avoiding the toxicities associated with inhibition of the normal functions of KRS.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-15782
    KRS-67LR Inhibitor