Table 1.
Compound structures, KRASG12C binding measured by mass spectrometry (MS), and biochemical IC50 measurements.
|
| ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
|
Cmpd |
R1 |
R2 |
R3 |
W |
X |
Y |
Z |
MS assay [% binding] |
IC50 KRASG12C [μM] |
IC50 KRASWT [μM] |
|
1 |
H |
|
H |
C |
|
CH |
N |
80 |
2.8 |
>20 |
|
2 |
H |
|
H |
C |
|
CH |
CH |
35 |
4.7 |
>20 |
|
3 |
H |
|
H |
C |
|
CH |
CH |
34 |
5.0 |
>20 |
|
4 |
H |
|
H |
C |
|
CH |
CH |
0 |
>20 |
>20 |
|
5 |
H |
|
H |
C |
|
CH |
CH |
60 |
8.0 |
>20 |
|
6 |
H |
|
H |
C |
|
CH |
CH |
20 |
>16 |
>20 |
|
7 |
Cl |
|
H |
C |
|
CH |
CH |
51 |
14.6 |
>20 |
|
8 |
H |
|
H |
C |
|
CH |
CH |
0 |
>20 |
>20 |
|
9 |
H |
|
H |
C |
|
CH |
CH |
0 |
>20 |
>20 |
|
10 |
H |
|
CH3 |
C |
|
CH |
CH |
11 |
>20 |
>20 |
|
11 |
H |
|
H |
C |
|
N |
CH |
59 |
4.90 |
>20 |
|
12 |
OH |
|
H |
C |
|
CH |
CH |
0 |
>20 |
>20 |
|
13 |
– |
|
H |
N |
|
CH |
CH |
73 |
1.3 |
>20 |
