The term'undruggable'was coined to describe proteins that could not be targeted
pharmacologically. However, progress is being made to'drug'many of these targets, and …

KRAS is the most frequently mutated oncogene in human cancer. In addition to holding this
distinction, unsuccessful attempts to target this protein have led to the characterization of …

Kinases are highly regulated enzymes with diverse mechanisms controlling their catalytic
output. Over time, chemical discovery efforts for kinases have produced ATP-competitive …

The mammalian target of rapamycin (mTOR) regulates cell growth and survival by
integrating nutrient and hormonal signals. These signaling functions are distributed between …

The kinase Akt plays a central role as a regulator of multiple growth factor input signals, thus
making it an attractive anticancer drug target. A-443654 is an ATP-competitive Akt inhibitor …

Summary Phosphoinositide 3-kinases (PI3-Ks) are an important emerging class of drug
targets, but the unique roles of PI3-K isoforms remain poorly defined. We describe here an …

Protein kinases have proved to be largely resistant to the design of highly specific inhibitors,
even with the aid of combinatorial chemistry. The lack of these reagents has complicated …

Somatic mutations in the small GTPase K-Ras are the most common activating lesions found
in human cancer, and are generally associated with poor response to standard therapies …

Tumours with mutant BRAF are dependent on the RAF–MEK–ERK signalling pathway for
their growth,,. We found that ATP-competitive RAF inhibitors inhibit ERK signalling in cells …

Oncogenic tyrosine kinases have proved to be promising targets for the development of
highly effective anticancer drugs. However, tyrosine kinase inhibitors (TKIs) against the …