Project Details
Projekt
The mRNA binding protein IMP2/IGF2BP2 as a target for anti-cancer therapy: target validation and hit-to-lead optimization
Subject Area
Pharmacy
Term
since 2021
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 453246190
The mRNA binding protein IGF2BP2/IMP2 is overexpressed inseveral types of cancer and has been shown to exhibit several tumorpromotingactions: IMP2 promotes tumorigenesis, cancerprogression, genomic instability, tumor cell growth, andchemoresistance. These properties as well as its predominantlyoncofetal expression make it an interesting therapeutic target for thetreatment of cancer. The rationale of this project is based oncomprehensive joint preliminary data by the two applicants, whoexhibit synergistic exertises. A screening assay was established totest for compounds, which are able to antagonize the interaction ofIMP2 with its target RNA sequences. Screening of four librariesrevealed a number of hits, which were verified employing biophysicaland biological assays. The aims of this project are the (I) further targetvalidation, (II) mode and site of interaction analysis, and (III) hit tolead optimization of compounds inhibiting the interaction of IMP2 withits targets. The target validation will be performed by comprehensive2D and 3D live cell analyses upon knockout and overexpression ofIMP2. Screening hits and optimized compounds will be tested in vitroand in vivo, structural information of interaction sites will be obtained,and compounds will be optimized with medicinal chemistry. Theproject represents an inter-disciplinary and synergistic combination ofmolecular and cell biology techniques from a molecular pharmacologygroup with chemical/synthetic and biophysical expertise from amedicinal chemistry group.
DFG Programme
Research Grants
International Connection
Austria, Switzerland, USA
Cooperation Partners
Jeetayu Biswas, Ph.D.; Dr. Jeffrey A. Chao; Professorin Dr. Johanna Pachmayr
