1. Academic Validation
  2. The crystal structure of MPK38 in complex with OTSSP167, an orally administrative MELK selective inhibitor

The crystal structure of MPK38 in complex with OTSSP167, an orally administrative MELK selective inhibitor

  • Biochem Biophys Res Commun. 2014 Apr 25;447(1):7-11. doi: 10.1016/j.bbrc.2014.03.034.
Yong-Soon Cho 1 Yingjin Kang 1 Kuglae Kim 1 Young-Je Cha 1 Hyun-Soo Cho 2
Affiliations

Affiliations

  • 1 Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea.
  • 2 Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea. Electronic address: hscho8@yonsei.ac.kr.
Abstract

Murine protein serine/threonine kinase 38 (MPK38), also known as maternal embryonic leucine zipper kinase (MELK), has been associated with various human cancers and plays an important role in the formation of Cancer Stem Cells. OTSSP167, a MELK selective inhibitor, exhibits a strong in vitro activity, conferring an IC50 of 0.41nM and in vivo effect on various human Cancer xenograft models. Here, we report the crystal structure of MPK38 (T167E), an active mutant, in complex with OTSSP167 and describe its detailed protein-inhibitor interactions. Comparison with the previous determined structure of MELK bound to the nanomolar inhibitors shows that OTSSP167 effectively fits into the active site, thus offering an opportunity for structure-based development and optimization of MELK inhibitors.

Keywords

Inhibitors; MELK; MPK38; OTSSP167.

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