We will be making a regular point of providing you with the latest publications, reports and papers including developments and products from BioSolveIT and its associated owners.
New leads for selective GSK-3 inhibition: pharmacophore mapping and virtual screening studies.
Dhilon S. Patel and Prasad V. Bharatam
J. Comput.-Aided Mol. Des. 20, 55-66 (2006)
The authors present a very welcome study on new leads against the glycogen synthase kinase 3 receptor, which is important for the treatment of diabetes mellitus, cancer, chronic inflammation and other human diseases. They used known inhibitors to create a pharmacophore pattern with the distance comparison method, and carried out a final screening of the NCI, Maybridge and Leadquest library using FlexX as the docking program of choice.
Current Status of Virtual Screening as Analysed by Target Class.
Martin J. Stoermer
Med. Chem. 2, 89-112 (2006)
The author provides a good overview of successful applications of drug discovery software. Among other software tools, the author mentions some very nice examples accomplished using BioSolveIT's docking engine FlexX and its modules. Researchers at AstraZeneca for example used FlexX-Pharm to discover 36 compounds in four different chemical classes that showed IC50s in the range of 110nM to 68M in cell-based assays against Chk-1 kinase. Rajnarayanan et al. used FlexX to discover potential inhibitors against the SARS protease. Fatorusso et al. found a compound inhibiting caspase-8 with a Ki of 2.7 µM using a combined docking protocol of FlexX and Gold. Virag and coworkers used FlexX-Pharm to simultaneously dock molecules from the WDI into ER alpha structures to identify agonists and antagonists from decoy structures. The paper lists a few other success stories of computer-aided drug design using FlexX or FlexS.
Successful computer guided planned synthesis of (4R)-thiazolidine carboxylic acid and its 2-substituted analogues as urease inhibitors.
KM Khan et. al.
Mol. Divers. 10, 223-231 (2006)
The authors identified (4R)-thiazolidines carboxylic acid and its 2-substituted analogs as active inhibitors of urease using Grid and FlexX, by screening a 90,000 compound database and screening the top scoring compounds in the wet lab. Using this computer-guided planned synthesis, it turned out that of ten synthesized ligands, (4R)-thiazolidine was found to be the most active with an IC50 value of 4.23 µM.