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4

Compound

erbB -2

EGFR

dissociation

EGFR activity

Ki (nM)

Ki (nM)

rates

post compound

Unusual Kinetic Behavior of Tykerb

Wood et al Cancer Res 2004: 64, 6652

T1/2

= 300 min

T1/2

< 10 min

80

Tykerb

13 +/ - 1

3.0 +/ - 0.2

Tarceva

870 +/ - 90

0.4 +/ - 0.1

60

washout

15% @ 72h

100% @ 24h

40000

30000

20000

10000

No Inhibitor GW 572016 OSI 774 PKI 166 ZD 1839

0

0

20

40

Time (min)

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