ATP-Competitive Inhibitors of MAP Kinases

Inhibitors binding in the ATP site are a very promising and successful drug design strategy in the field of kinase. Several ATP-competitive inhibitors are in the market for the treatment of cancer and other diseases. Many research institutes discovered preclinical ATP-competitive inhibitors of MAP kinases using fragment-based drug design or optimization of their initial hit from high-throughput screening to improve in vitro potency only but lack PK profile. Some investigators from pharmaceutical companies discovered lead compounds using X-ray structure-based drug design strategy. A few industries disclosed clinical candidates from hit to lead with improved potency and favorable PK profile. Readers should gain vast information about how an initial hit becomes a clinical candidate.