Small cell-permeant inhibitors of protein kinases have become valuable reagents to investigatethe physiological roles of protein kinases, because they can be used simply and rapidly to block endogenouskinase activity in normal cells and tissues, as well as transformed cell lines. There are no potent inhibitors ofMKP-1, which dephosphorylates p38, JNK, and this is unfortunate because MKP-1 has been associatedwith human neoplasia and is an attractive potential therapeutic target. The active sites of MKP-1 werepredicted and screened with synthesized analogs and related structures are obtained from PUBCHEM. Thebest hits were the analogs NU-126, NU-154 and these compounds were docked with the protein usingAUTODOCK. MKP-1 constitutes an exciting, novel potential therapeutic target for Rheumatoid Arthritis.There is perfect active site information about the protein and selective inhibitor, so this docking workprovides insights to develop new drug for the disease, rheumatoid arthritis.