791824-10-7Relevant articles and documents
Novel lead structures for p38 MAP kinase via FieldScreen virtual screening
Cheeseright, Timothy J.,Holm, Melanie,Lehmann, Frank,Luik, Sabine,Gottert, Marcia,Melville, James L.,Laufer, Stefan
experimental part, p. 4200 - 4209 (2010/01/16)
p38 MAP kinase has received considerable interest in the pharmaceutical industry and remains a valid and interesting target for the treatment of inflammation. To discover novel p38 inhibitors, we applied the ligand-based virtual screening technique, FieldScreen, to 1.2 million commercially available compounds. Fifty-eight diverse compounds were selected for biological analysis, using molecular field similarity to known inhibitors, while explicitly removing any structure that shared a scaffold with previously reported p38 inhibitors. Of these, 11 (19%) showed ≥20% inhibition of p38 at 10 μM. We chose to prepare analogues of two distinct chemical series resulting in a potential lead compound with pIC50 of 6.4. Modeling of SAR using FieldAlign, a ligand alignment protocol, was used to rationalize the SAR of the series of thiadiazole based inhibitors.
