Anticancer osmium complex inhibitors of the HIF-1α and p300 protein-protein interaction.

Title Anticancer osmium complex inhibitors of the HIF-1α and p300 protein-protein interaction.
Authors Yang, C.; Wang, W.; Li, G.D.; Zhong, H.J.; Dong, Z.Z.; Wong, C.Y.; Kwong, D.W.J.; Ma, D.L.; Leung, C.H.
Journal Sci Rep
DOI 10.1038/srep42860
Abstract

The hypoxia inducible factor (HIF) pathway has been considered to be an attractive anti-cancer target. One strategy to inhibit HIF activity is through the disruption of the HIF-1α-p300 protein-protein interaction. We report herein the identification of an osmium(II) complex as the first metal-based inhibitor of the HIF-1α-p300 interaction. We evaluated the effect of complex 1 on HIF-1α signaling pathway in vitro and in cellulo by using the dual luciferase reporter assay, co-immunoprecipitation assay, and immunoblot assay. Complex 1 exhibited a dose-dependent inhibition of HRE-driven luciferase activity, with an IC50 value of 1.22 μM. Complex 1 interfered with the HIF-1α-p300 interaction as revealed by a dose-dependent reduction of p300 co-precipitated with HIF-1α as the concentration of complex 1 was increased. Complex 1 repressed the phosphorylation of SRC, AKT and STAT3, and had no discernible effect on the activity of NF-κB. We anticipate that complex 1 could be utilized as a promising scaffold for the further development of more potent HIF-1α inhibitors for anti-cancer treatment.

Citation Yang, C.; Wang, W.; Li, G.D.; Zhong, H.J.; Dong, Z.Z.; Wong, C.Y.; Kwong, D.W.J.; Ma, D.L.; Leung, C.H..Anticancer osmium complex inhibitors of the HIF-1α and p300 protein-protein interaction..

Related Elements

Osmium

76 Os 190.230000000 Osmium

See more Osmium products. Osmium (atomic symbol: Os, atomic number: 76) is a Block D, Group 8, Period 6 element with an atomic weight of 190.23. Osmium Bohr ModelThe number of electrons in each of osmium's shells is [2, 8, 18, 32, 14, 2] and its electron configuration is [Xe] 4f14 5d6 6s2. The osmium atom has a radius of 135 pm and a Van der Waals radius of 216 pm. Osmium was discovered and first isolated by Smithson Tennant in 1803. Elemental OsmiumIn its elemental form, osmium has a silvery blue cast apperance. Osmium has the highest melting point and the lowest vapor pressure of any of the platinum group of metals it is also the densest naturally ocurring element. Osmium is the least abundant stable element in the earth's crust. It is found in the alloys osmiridium and iridiosmium and as a free element. The origin of the name Osmium comes from the Greek word osme, meaning a smell or odor.

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