Mohamed Abdelsalam
M.Sc. Mohamed Abdelsalam
Dr. Mohamed Abdelsalam, PhD
Tel ++49 345 55 25188
e-mail: mohamed.abdelsalam(at)pharmazie.uni-halle.de
Development of chemical probes to dissect the functions of class I and IIb HDACs in FLT3-ITD-positive leukemic cells
Mutations in the FMS-related tyrosine kinase (FLT3) cause AML with poor patient prognosis. Epigenetic modifiers of the histone deacetylase (HDAC) family control the development and survival of normal and transformed blood cells. Inhibitors of zinc-dependent HDACs (HDACi) are approved drugs against subtypes of leukemia and lymphoma. There are 11 zinc-dependent HDACs in mammalian cells and ongoing intense research is done to dissect their precise functions. In the present project we will develop novel, highly specific inhibitors of HDACs and FLT3 to analyze their role in cancer cells.
Another starting point is the development of protein-degrading agents, the so-called PROTACs, for the HDACs and FLT3-ITD under investigation. PROTACs are designed to specifically degrade the target proteins in the cancer cells under investigation in order to better understand their biological role.
Kooperation: Prof. Dr. Oliver Krämer, Institute of Toxikologie, Universität Mainz
Publications
M. Abdelsalam, M. Zmyslia, K. Schmidtkunz, A. Vecchio, M. Zessin, M. Schutkowski, M. Jung, C. Jessen-Trefzer, W. Sippl. Design and synthesis of bioreductive prodrugs of class I histone deacetylase inhibitors and their biological evaluation in virally transfected acute myeloid leukemia cells. Arch Pharm (Weinheim). e2300536, 2023. doi:10.1002/ardp.202300536 .
M. Abdelsalam, H. S. Ibrahim, L. Krauss, M. Zessin, A. Vecchio, S. Hastreiter, M. Schutkowski, G. Schneider, W. Sippl. Development of pyrazine-anilinobenzamides as histone deacetylase HDAC1-3 selective inhibitors and biological testing against pancreas cancer cell lines. Methods Mol Biol. 2589:145-155, 2023. doi:10.1007/978-1-0716-2788-4_10
M. Abdelsalam, M. Zessin, M. Schmidt, M. Schutkowski and W. Sippl. N1-(2-Amino-4-fluorophenyl)-N4-(3-(2-(2-(3-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4yl)amino)propoxy)ethoxy)ethoxy)propyl)terephthalamide. Molbank 2022, 2022(4), M1501; https://doi.org/10.3390/M1501
E. F. Bülbül, J. Melesina, H. S. Ibrahim, M. Abdelsalam, A. Vecchio, D. Robaa, M. Zessin, M. Schutkowski, and W. Sippl.
Docking, Binding Free Energy Calculations and in vitro Characterization of Pyrazine Linked 2-Aminobenzamides as new Class I Histone Deacetylase (HDAC) Inhibitors.
Molecules. 2022 Apr 14;27(8):2526. doi:10.3390/molecules27082526 .
E. Ghazy, M. Abdelsalam, D. Robaa, R.J. Pierce, W. Sippl.
Histone deacetylase (HDAC) inhibitors for the treatment of Schistosomiasis.
Pharmaceuticals 15(1), 80, 2022. https://doi.org/10.3390/ph15010080
H. Ibrahim, M. Abdelsalam, Y. Zeyn, M. Zessin, E F. Bülbül, A. M. Mustafa, M. A. Fischer, P. Zeyen, A. Vecchio, P. Sun, F. Erdmann, M. Schmidt, D. Robaa, C. Romier, M. Schutkowski, O. H. Krämer, and W. Sippl.
Synthesis and structure-activity relationship studies of pyrazine linked 2-aminobenzamides as new class I selective histone deacetylase (HDAC) inhibitors and their biological characterization in leukemic cellsInt.
J. Mol. Sci. 23(1), 369, 2022. https://doi.org/10.3390/ijms23010369
Full publication list