Small GTPases use GDP/GTP alternation to actuate a variety of functional switches that are
pivotal for cell dynamics. The GTPase switch is turned on by GEFs, which stimulate …

Guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs)
regulate the activity of small guanine nucleotide-binding (G) proteins to control cellular …

The discovery of small-molecule inhibitors requires suitable binding pockets on protein
surfaces. Proteins that lack this feature are considered undruggable and require innovative …

Guanine nucleotide-exchange factors (GEFs) are directly responsible for the activation of
Rho-family GTPases in response to diverse extracellular stimuli, and ultimately regulate …

Drugs that directly impede the function of driver oncogenes offer exceptional efficacy and a
therapeutic window. The recently approved mutant selective small-molecule cysteine …

Ras genes are the most common targets for somatic gain-of-function mutations in human
cancer. Recently, germline mutations that affect components of the Ras–Raf–mitogen …

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 …

RAS is the most frequently mutated oncogene in human cancers, with mutations in about
30% of all cancers. RAS exists in three different isoforms (K-RAS, H-RAS and N-RAS) with …

It is thought that KRAS oncoproteins are constitutively active because their guanosine
triphosphatase (GTPase) activity is disabled. Consequently, drugs targeting the inactive or …

The RASopathies are a group of disorders caused by a germline mutation in one of the
genes encoding a component of the RAS/MAPK pathway. These disorders, including …