Table 1
Biochemical and cellular activities of compounds 8, 9, 10 and 11
Compound
R1
P-MET WT IC
50
(nM)
MKN-45
proliferation
IC
50 (nM)
L1195V IC
50
(nM)
M1250T IC
50
(nM)
Y1230H IC
50
(nM)
logD
(pH 7.4)
8
NH
2
10
81
9,000
245
>10,000
>4.6
9
N
H
O
*
3
7
61
13
883
4.7
10
N
O
N
H
O
*
6
12
318
93
1,172
4.3
11
(SAR125844)
N
O
N
H
N
H
O
*
4
7
64
6
204
4.2
P-MET WT: IC50 measured using protein phosphorylation in a biochemical assay. MKN-45 Proliferation: IC50 measured in proliferation assay using MKN-45
cell line. L1195V, M1250T and Y1230H: IC50 measured using corresponding MET mutants in a biochemical assay. logD measured experimentally by high
performance liquid chromatography (HPLC) (Xterra MS C18 column)
Achieving High Levels of Selectivity for Kinase Inhibitors
107