Table 1.

Kinase activity of R547

A. Inhibitory activity of R547 against a panel of in-house protein kinases
KinaseKi* (nmol/L) ± SD
CDK4/cyclin D11 ± 0.1
CDK2/cyclin E3 ± 0.8
CDK1/cyclin B2 ± 0.8
PKA>5,000
PKB>5,000
PKCα>5,000
PKCβ>5,000
FYN>5,000
EPHB3>5,000
SGK>5,000
p38>50,000
GSK3β8,000
KDR>5,000
FGFR>5,000
EGFR>5,000
PDGF>5,000
MAPK2>50,000
IGFR>5,000
SRC>5,000
FAK>5,000
AURORA>5,000
B. Inhibitory activity of R547 in the Upstate kinase selectivity screen
Kinase
IC50 (nmol/L)
Kinase
IC50 (nmol/L)
Kinase
IC50 (nmol/L)
CDK2/cyclin A0.1FGFR3>10,000PKA>10,000
CDK2/cyclin E0.4FGFR4>10,000PKBβ>10,000
CDK1/cyclin B0.2Flt1>10,000PKBγ>10,000
CDK3/cyclin E0.8Flt3>10,000PKCα>10,000
CDK5/p350.1Fms>10,000PKCβI>10,000
CDK6/cyclin D34.0Fyn>10,000PKCβII>10,000
CDK7/cyclin H171Hck>10,000PKCγ>10,000
GSK3α46IGFR-1R>10,000PKCδ>10,000
GSK3β260IKKα>10,000PKCε>10,000
Abl (m)>10,000IKKβ>10,000PKCη>10,000
Abl>10,000IR>10,000PKCι>10,000
Abl (T315I)>10,000IRAK4>10,000PKCμ>10,000
ALK>10,000JNKα1>10,000PKC[thetas]>10,000
AMPK (r)>10,000JNK2α2>10,000PKCζ>10,000
Arg>10,000JNK3>10,000PKD2>10,000
Arg (m)>10,000Lck>10,000Plk3>10,000
ASK1>10,000Lyn>10,000PRAK>10,000
Aurora-A>10,000Lyn (m)>10,000PRK2>10,000
Axl>10,000MAPK1>10,000Ret>10,000
Blk (m)>10,000MAPK2>10,000ROCK-I>10,000
Bmx>10,000MAPKAP-K2>10,000ROCK-II>10,000
BTK>10,000MAPKAP-K3>10,000Ron>10,000
CaMKII (r)>10,000MEK1>10,000Ros>10,000
CaMKIV>10,000Met>10,000Rse>10,000
CHK1>10,000MKK4 (m)>10,000Rsk1>10,000
CHK2>10,000MKK6>10,000Rsk1(r)>10,000
CK1(y)>10,000MKK7β>10,000Rsk2>10,000
CK1δ8,270MSK1>10,000Rsk3>10,000
CK2>10,000MST2>10,000SAPK2a>10,000
c-RAF>10,000NEK2>10,000SAPK2b>10,000
CSK>10,000NEK6>10,000SAPK3>10,000
cSRC>10,000NEK7>10,000SAPK4>10,000
DDR2>10,000P70S6K>10,000SGK>10,000
EGFR>10,000PAK2>10,000Syk>10,000
EphA2>10,000PAK4>10,000TAK1>10,000
EphB2>10,000PAR-1Bα>10,000Tie2>10,000
EphB4>10,000PDGFRα>10,000TrkA>10,000
ErbB4>10,000PDGFRβ>10,000TrkB>10,000
Fes>10,000PDK1>10,000Yes>10,000
Fgr>10,000Pim-1>10,000ZAP-70>10,000
FGFR1>10,000P13Kγ>10,000
  • * Ki = IC50 / (1 + S / Km), where S is the substrate ATP concentration and Km is the Michaelis-Menten constant for ATP; mean of at least two separate determinations.