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

Yong Soon Cho, Yingjin Kang, Kuglae Kim, Young Je Cha, Hyun Soo Cho

Research output: Contribution to journalArticle

15 Citations (Scopus)

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 0.41 nM 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.

Original languageEnglish
Pages (from-to)7-11
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume447
Issue number1
DOIs
Publication statusPublished - 2014 Apr 25

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Leucine Zippers
Protein-Serine-Threonine Kinases
Phosphotransferases
Crystal structure
Mothers
Neoplastic Stem Cells
Stem cells
Heterografts
Inhibitory Concentration 50
Catalytic Domain
Neoplasms
Embryonic Structures
1-(6-(3,5-dichloro-4-hydroxyphenyl)-4-((4-((dimethylamino)methyl)cyclohexyl)amino)-1,5-naphthyridin-3-yl)ethanone
Proteins

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

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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 0.41 nM 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.",
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The crystal structure of MPK38 in complex with OTSSP167, an orally administrative MELK selective inhibitor. / Cho, Yong Soon; Kang, Yingjin; Kim, Kuglae; Cha, Young Je; Cho, Hyun Soo.

In: Biochemical and Biophysical Research Communications, Vol. 447, No. 1, 25.04.2014, p. 7-11.

Research output: Contribution to journalArticle

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T1 - The crystal structure of MPK38 in complex with OTSSP167, an orally administrative MELK selective inhibitor

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AU - Kang, Yingjin

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AU - Cho, Hyun Soo

PY - 2014/4/25

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