TABLE 1

Selectivity of Chiron GSK-3 inhibitors

KinaseSpeciesGroup% IdentityChir98014 IC50 (mmol/l)Chir98030 IC50 (nmol/l)Chir99021 IC50 (nmol/l)
GSK-3αHumanCMGC3910.6510
GSK-3βHumanCMGC31000.589.96.7
Murine balb/c28
Murine db/db6.4
Rat fa/fa7.4
Human0.87 (Ki)9.8 (Ki)
cdc2HumanCMGC1303,7008,800
erk2MouseCMGC231>10,000>10,000
PKC-αHumanAGC222>10,000>10,000
PKC-ζHumanAGC219>10,000
akt1/PKBHumanAGC321>5000>10,000
p70 S6KRatAGC622>1000>10,000
p90 RSK2RabbitAGC6, CAMK 12622>10,000>10,000
c-srcPTK0119>1000
tie2HumanPTK1318>5000>5,000
flt1HumanPTK1417>5000>5,000
KDRHumanPTK1418>2000>5,000
bFGFRTKHumanPTK1520>1000>5,000
IGF1RTKHumanPTK1616>2000>10,000
insulin RTKHumanPTK1616>2000>10,000
AMPkinaseRatOPK22>10,000
pdk1HumanOPK23>10,000
chk1HumanOPK21>10,000>10,000
CK1-εHumanOPK17>5,000>5,000
DNA protein kinaseHumanPl3KLow>10,000
PI 3-kinaseHumanPl3KLow>2,000>10,000