Targeting CRAF kinase in anti-cancer therapy: progress and opportunities

Table 1 Classification of selected RAF1 point mutants

Mutations	Location	Kinase functional change	Ref.
D468A	Catalytic loop	Kinase dead	[1]
K375M	β3-K of K/E/D/D	Kinase dead	[1]
D486A	DFG-loop	Kinase dead	[2]
R391W	αC-helix	Kinase activated	[3]
P261A	Kinase domain	Oncogenic, sensitivity to combined type II RAF and MEK inhibitors	[4]
G361A	Glycine rich loop	Enhanced RAF dimerization and increased kinase activity, resistance to type I RAF inhibitors	[5]
S257W, S259F	CRD	Sensitivity to Sorafenib	[6]
S257P, P261T, G361A	CRD, Glycinerich Loop	Resistance to RAF inhibitors	[7]
E478K	Catalytic loop	Constitutively heterodimerize	[2]
E401H	Kinase domain	Defective in dimerization	[2]
S427G, I448V	Kinase domain	Activating variants	[8]

DFG-loop, Aspartate-Phenylalanine-Glycine loop; CRD, Carbohydrate Recognition Domain.

ISSN: 1476-4598