Table 3.
GDP/GTP‐exchange and cellular activities of new scaffolds and derivatives.
|
(GDP)K‐Ras4B/SOS exchange (IC50 [μM]) |
|
Cellular activities (IC50 [μM]) |
||||||
|---|---|---|---|---|---|---|---|---|
|
|
G12D |
WT |
WT %CRTL 3 mM |
SNU‐1 (G12D) |
NCI‐H441 (G12 V) |
HCT15 (G13D) |
H358 (G12 C) |
A549 (G12S) |
|
Benzimidazole benzofuran scaffold | ||||||||
|
12 |
340±72 |
1099±381 |
75 % |
34.5±2.1 |
47.4±3.0 |
37.7±0.4 |
37.7±1.3 |
45.3±1.5 |
|
13 |
409±32 |
334±5 |
n.d. |
52.7±0.3 |
54.5±0.2 |
n.d. |
n.d. |
50.3±2,0 |
|
29 |
769 [a] |
993±388 |
n.d. |
30.5±0.2 |
42.3±7.6 |
25.6±3.7 |
31.4±1.2 |
32.8±7.3 |
|
Benzimidazole phenol scaffold | ||||||||
|---|---|---|---|---|---|---|---|---|
|
14 a |
320±17 |
304 [a] |
n.d. |
|
|
|
|
|
|
14 b |
>3000 |
>3000 |
70 |
>300 |
>300 |
n.d. |
n.d. |
>300 |
|
14 c |
1069±130 |
493±31 |
77 |
>300 |
>300 |
n.d. |
n.d. |
>300 |
|
14 d |
1453±348 |
1758±215 |
70 |
>300 |
>300 |
n.d. |
n.d. |
>300 |
|
14 e |
>3000 |
>3000 |
77 |
265±14 |
>300 |
n.d. |
n.d. |
>300 |
|
14 f[ a] |
356[a] |
>3000 |
95 |
>30 |
>30 |
n.d. |
n.d. |
>30 |
|
14 g |
776±57 |
380±59 |
69 |
>300 |
>300 |
n.d. |
n.d. |
>300 |
|
30 |
873±294 |
1017±119 |
89 |
75.7±3.4 |
145±37 |
n.d. |
n.d. |
103±5 |
|
31 |
1272±99 |
1965[a] |
95 |
|
|
|
|
|
Data are shown as mean±SD of independent repeats (2–5 times). [a] Single measurements due to limited substance availability. [b] Due to substance limitations or solubility problems testing was not possible at higher concentrations.