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Antagonism of mTOR activity by a kinetically inert rhodium(III) complex
Zhong H.-J.1,2; Leung K.-H.1; Liu L.-J.2; Lu L.1; Chan D.S.-H.1; Leung C.-H.2; Ma D.-L.1,2
2014
Source PublicationChemPlusChem
ISSN21926506
Volume79Issue:4Pages:508-511
Abstract

Kinetically inert Group 9 metal complexes have found emerging use as inhibitors of protein kinases or as modulators of protein-protein interactions. A series of cyclometalated rhodium(III) and iridium(III) complexes was investigated as inhibitors of mammalian target of rapamycin (mTOR) activity. Cell-free and cell-based experiments revealed rhodium(III) complex 1 to be a potent mTOR inhibitor (IC50=0.01 μM in the cell-free system), with potency comparable to that of rapamycin. The inhibition by complex 1 was found to be dependent on FK506-binding protein 12 (FKBP12), which suggests that complex 1 may behave as a modulator of the mTOR-FKBP12 interaction. Preliminary structure-activity relationships indicated that the donor ligand and the nature of the metal center are important determinants for mTOR inhibitory activity. Rhodium(III) complex 1 represents the first metal-based inhibitor of mTOR activity, and demonstrates the potential of kinetically inert Group 9 complexes as protein-protein interaction modulators. Limiting activity: The first metal-based inhibitor of mammalian target of rapamycin (mTOR) activity has been found. The cyclometalated rhodium(III) complex 1 (see scheme) inhibits mTOR activity in cell-free and cell-based systems. The size and hydrophobicity of the N N donor ligand and the nature of the metal center are determinants for mTOR inhibitory activity. The inhibitory effect of 1 is also dependent on FK506-binding protein 12.

KeywordBioorganometallic Chemistry Group 9 Metal Complexes Inhibitors Rhodium Structure-activity Relationships
DOI10.1002/cplu.201400014
URLView the original
Indexed BySCIE
Language英语
WOS Research AreaChemistry
WOS SubjectChemistry, Multidisciplinary
WOS IDWOS:000334114200002
The Source to ArticleScopus
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Cited Times [WOS]:26   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorLeung C.-H.; Ma D.-L.
Affiliation1.Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong (P. R. China)
2.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao (P. R. China)
First Author AffilicationInstitute of Chinese Medical Sciences
Corresponding Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Zhong H.-J.,Leung K.-H.,Liu L.-J.,et al. Antagonism of mTOR activity by a kinetically inert rhodium(III) complex[J]. ChemPlusChem,2014,79(4):508-511.
APA Zhong H.-J.,Leung K.-H.,Liu L.-J.,Lu L.,Chan D.S.-H.,Leung C.-H.,&Ma D.-L..(2014).Antagonism of mTOR activity by a kinetically inert rhodium(III) complex.ChemPlusChem,79(4),508-511.
MLA Zhong H.-J.,et al."Antagonism of mTOR activity by a kinetically inert rhodium(III) complex".ChemPlusChem 79.4(2014):508-511.
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