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Novel inhibitors for CYP51 of Mycobacterium tuberculosis
Mycobacterium tuberculosis lanosterol demethylase inhibitor complex 2cib
Nasser Eddine A, von Kries JP, Podust MV, Warrier T, Kaufmann SH, Podust LM. X-ray structure of 4,4'-dihydroxybenzophenone mimicking sterol substrate in the active site of sterol 14alpha -demethylase (CYP51). J Biol Chem. 2008 May 30;283(22):15152-9. Epub 2008 Mar 26
Inhibitors of the protein tyrosin phosphatase Shp2 block scattering of MDCK cells in a metastasis model
Inhibitors of HGF/SF induced cell scattering of MDCK colonies in 384well MTP´s:
Cells are stained for actin with phalloidinB (red) , for total cells with CMFDA (green, live cell tracker) and for nuclei with Hoechst 3342 (blue) . Images are documented and analyzed with the ArrayScan VTi. In absence of HGF/SF (-SF, left) cells build colonies, after addition of Hepatocyte Growth Factor (+SF, 3 units, 24 hrs) cells in colonies detach from each other and get motile. This process resembles metasasis of tumor cells in cancer development. In presence of Shp2 inhibitors this process is blocked.
K. Hellmuth, S. Grosskopf, C. T. Lum, M. Würtele, N. Röder, J. P. von Kries, M. Rosario, J. Rademann, W. Birchmeier. (2008) Proc. Nat. Acad. Sci. USA , 105, 7275-7280.
Argyrin-A: A highly selective proteasome inhibitor and potent antitumor lead
HUVEC-cells stained for paxilin (green) and actin (red):
Top: control showing green focal adhesions. Bottom: after treatment with Argyrin-A (insert:2D structure).
Nickeleit, I.; Zender, S.; Sasse, F.; Geffers, R.; Brandes, G.; Sörensen, I.; Steinmetz, H.; Kubicka,S.; Carlomagno, T.; Menche, D.; Buer, J.; Gossler, A.; Manns, M.P.; Kalesse, M.; Frank, R.;Malek, N.P. (2008). Argyrin A reveals a critical role for the tumor suppressor protein p27kip1 in mediating anti-tumor activities in response to proteasome inhibition. Cancer Cell. 14:23-35.