Table 1.

Selectivity of R428 in cell-based and biochemical assays

KinaseKinase family and groupFold over Axl
BiochemicalCell-based
MerTK1650
Tyro3TK14>100
Tie-2TK3ND
Flt-1, Flt-4TK8.0, 5.5ND
Insulin receptorTK>50>100
VEGFR2TK3433
EGFR, HER2TK>100>100, ND
PDGFRβTK>100>100
RetTK9ND
MetTK>100ND
AblTK9.3>100
c-Src, JAK3TK>100ND, >50
c-rafTKL>100ND
MEK1, Pak2STE>100ND
CK1γ2, CK2CK1>100ND
p70S6K, PKCγ, PKCεAGC>100ND
AMPK, CAMKllβ, MLCKCAMK>100ND
CDK2, ERK1CMGC>100ND

NOTE: Biochemical: fold difference between R428 IC50 in off-target versus Axl biochemical assays. Cell-based: fold difference between R428 EC50 in off-target versus Axl cell-based assays. Phosphorylation-based signaling assays were used except for Abl and JAK3 (proliferation readout).

Abbreviation: ND, not determined; TK, tyrosine kinase; TKL, tyrosine kinase-like; STE, homologues of yeast Sterile 7, Sterile 11, Sterile 20 kinases; CK1, Casein kinase 1; AGC, containing PKA, PKG, PKC families; CAMK, calcium/calmodulin-dependent protein kinases; CMGC, containing CDK, MAPK, GSK3, CLK families.