PT  - JOURNAL ARTICLE
AU  - Cheng, Caixia
AU  - Pan, Leyun
AU  - Dimitrakopoulou-Strauss, Antonia
AU  - Haberkorn, Uwe
AU  - Strauss, Ludwig
TI  - In silico modeling for virtual screening of new ligands for SSTR2
DP  - 2008 May 01
TA  - Journal of Nuclear Medicine
PG  - 302P--302P
VI  - 49
IP  - supplement 1
4099  - http://jnm.snmjournals.org/content/49/supplement_1/302P.2.short
4100  - http://jnm.snmjournals.org/content/49/supplement_1/302P.2.full
SO  - J Nucl Med2008 May 01; 49
AB  - 1286 Objectives: This study is aiming at the identification of new ligands for SSTR2. The enhanced expression of SSTR2 e.g. in endocrine tumors is the basis for the use of some compounds for diagnostic and therapeutic interventions. However, new ligands with better binding characteristics will improve both, tumor diagnostics and treatment. Methods: A dedicated multistep procedure was used to achieve new ligands. Search entries for our analysis were taken from ACD. Application of the criteria defined by the Lipinski rules reduced this initial set. Then, a set of 10 characterized ligands for SSTR2 were inserted in the search sample. As a next step in our hierarchical filtering, the ligands of the sample set had to match a predefined pharmacophore criterion, including Lys and Trp residues. All selected ligands were transformed from 2D to 3D. Finally, a dedicated software (FRED, OpenEye Scientific Software, Santa Fe, NM, USA) was applied to docking the sample to the SSTR2 structure (PDB ID: 1boj). Results: By trial docking, out of 16 compounds were found to match the proposed binding mode. By a cluster analysis and visual inspection, one compound was selected and subjected to structure-based optimization. Finally, a new ligand with better scores of docked poses compared with those characterized ligands was designed (Figure 1). Conclusions: One of the most important conclusions from this study is that the use of focused library that incorporate an initial scaffold improved the possibility of a successful virtual screening compared with random screening. This new ligand is promising to be a new lead compound. Further studies are performed to assess the synthesis of the substance and biodistribution.