| 01 |
3-Oxo-oxazinane |
HT29 (CRC, Brafv600E) |
IC50 1.7 nM |
In vitro tests against a variety of tumour cells revealed strong antiproliferative action with little genotoxicity, hERG inhibition, or CYP inactivation |
94
|
| QG56 (NSCL, HrasQ61L) |
IC50 9.5 nM |
| MIA PaCa-2 panc. |
IC50 3.3 nM |
| KrasG12C C32 Brafv600E
|
IC50 8.4 nM |
| Colo205 (CRC, Brafv600E) |
IC50 0.86 nM |
| 02 |
2-Aminopyrrole |
Colo205 |
EC50 0.012 (μM) |
Important hydrogen bonds are formed between the oxygen of the acetyl group and the NH groups of Val211 and Ser212 in the backbone |
126
|
| A375 (melanoma) |
EC50 0.014 (μM) |
| 03 |
Indazole |
HCT116 |
EC50 0.2 (nM) |
Bidentate interaction with the Ser212 residue of MEK1 |
127
|
| A375 |
EC50 0.4 (nM) |
| 04 |
Sulfamide |
HCT116 cell line |
IC50 8 (nM) |
The compound's safety profiles and DMPK profiles (PK profiles in three animal species, CYP inhibition, and CYP induction) were unaffected by the sulfamide moiety (hERG and AMES assays). Powerful repression of HCT116 cell development |
128
|
| 05 |
7-(Pyrimidin-2-yloxy)-2H-chromen-2-one |
HCT116 cell line |
IC50 17 (nM) |
No strong CYP inhibition activity |
129
|
| 06 |
Sulfamide |
A375 (B-Raf) |
IC50 4 (nM) |
Nanomolar cell potency of a very effective MEK inhibitor against B-RAF (V600E) and Ras-mutated cell lines |
130
|
| HCT116 (K-Ras) |
IC50 180 (nM) |
| 07 |
Bicyclic fused pyridine |
COLO-205 cell line |
IC50 1.95 (nM) |
Proven excellent in vitro Mek inhibitory activities |
131
|
| 08 |
Imidazo[1,5-a]pyrazine |
HCT116 cell line |
IC50 0.107 (nM) |
Rationalized by weaker interaction with the Ser-212 nitrogen due to the less basic, H-bond-accepting nitrogen |
132
|
| A375 cell line |
IC50 0.007 (nM) |
| 09 |
Phenylsulfonylfuroxan and coumarin oxadiazole |
A549 cell line |
IC50 0.024 (μM) |
The G2/M phase of the A2780 cell line's cell cycle was stopped |
133
|
| HeLa cell line |
IC50 0.053 (μM) |
| A2780 cell line |
IC50 0.014 (μM) |
| 10 |
Pyrrole-3-carbonitriles |
MCF-7 cells (breast) |
IC50 1.35 ± 0.01 (μM) |
It effectively inhibited proliferation in HT-29 (colon) and MCF-7 (breast) cells |
134
|
| HT-29 (colon) |
IC50 1.47 ± 0.04 (μM) |
| B16 cells |
IC50 4.61 ± 0.01 (μM) |
| 11 |
Sulfamide |
A375 (BRAF) |
IC50 13 (nM) |
BRAFV600E and Ras-mutant cell line resistance of cells (G13D) |
135
|
| HCT116 (K-Ras) |
IC50 277 (nM) |
| 12 |
9-Anilinoacridine phenyl-urea |
K562 cell line |
IC50 4.08 ± 0.14 (μM) |
Against K562 and HepG-2 tumor cells |
136
|
| HepG-2 cell line |
9.41 ± 1.09 (μM) |
| 13 |
N-(Benzyloxy)-1,3-diphenyl-1H-pyrazole-4-carboxamide |
HeLa cell line |
GI50 1.18 ± 0.06 (μM) |
This compound is most potent against the A549and Uo126 cancer cell lines |
137
|
| MCF-7 |
GI50 2.11 ± 0.12 (μM) |
| A549 cell line |
GI50 0.26 ± 0.02 (μM) |
| 293T cell line |
CC50 20.57 ± 1.48 (μM) |
| 14 |
2H-Chromen-2-one urea |
MCF7 cell line |
IC50 0.17 ± 0.07 (μM) |
MCF7 breast cancer cell line and A549 lung cancer cell line activity, but no Hsp90 inhibitory activity |
138
|
| A549 cell line |
IC50 0.15 ± 0.02 (μM) |
| MRC-5 cell line |
IC50 4.3 (μM) |
| 15 |
1-(1H-Pyrazolo[4,3-c]pyridin-6-yl) urea |
A375SM |
IC50 43 (nM) |
Strong tumor regression in BRAFV600E
|
139
|
| 16 |
Phenylsulfonylfuroxan and 3-benzyl coumarin |
HeLa cells |
IC50 2.8 (nM) |
Hardly affected the cell cycle of A2780 |
140
|
| SKOV3 cells |
IC50 8.3 (nM) |
| A549 cell |
IC50 3.7 (nM) |
| OVCA429 cells |
IC50 3.9 (nM) |
| OVCA433 cells |
IC50 3.3 (nM) |
| A2780 cells |
IC50 6.6 (nM) |
| MDA-MB-231 |
IC50 0.8 (nM) |
| MCF-7 cells |
IC50 2853 (nM) |
| KB cells |
IC50 3234 (nM) |
| 17 |
Benzofuran |
Colo-205 cells |
IC50 4.7 ± 1.5 (nM) |
Excellent in vivo efficacy in mouse Colo-205 tumour xenograft models |
116
|
| 18 |
Ursolic acid with hydrazide |
MDA-MB-231 |
IC50 0.12 ± 0.01 (μM) |
HeLa cells undergo apoptosis, and the cell cycle is stopped in the G0/G1 phase |
141
|
| HeLa cells |
IC50 0.08 ± 0.01 (μM) |
| SMMC-7721 cells |
IC50 0.34 ± 0.03 (μM) |
| QSG-7701 cells |
IC50 10.76 ± 0.72 (μM) |
| 19 |
Carbazole |
HEK293 cells |
IC50 8.9 ± 2.0 (μM) |
Greatly reduced cytotoxicity to HEK293 cells |
142
|
| A549 cells |
IC50 21.6 ± 6.1 (μM) |
| A375 cells |
IC50 7.7 ± 1.1 (μM) |
| HL60 cells |
IC50 17.2 ± 6.6 (μM) |
| 20 |
1,2,5-Oxadiazole 2-oxide |
MDA-MB-231 |
IC50 0.034 ± 0.007 (μM) |
Best cell growth inhibitory effect in MDA-MB-231 cells |
143
|
| HCT116 cells |
IC50 0.64 ± 0.30 (μM) |
| A549 cells |
IC50 1.35 ± 0.94 (μM) |
| Vero cells |
IC50 21.07 ± 1.32 (μM) |
| HL7702 cells |
IC50 5.62 ± 0.82 |
| 21 |
2H-Chromen-7-yl dimethylcarbamate |
A549 cells |
IG50 4.66 (μM) |
Activity against the A549 and HCT116 cell lines |
144
|
| HCT116 cells |
IG50 5.47 (μM) |
| 22 |
5-Phenylamino-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione |
A375 cells |
EC50 3.1 (nM) |
Fluorine-containing diol compounds had the most potent enzyme and cell activity |
82
|
| Colo-205 cells |
EC50 2.1 (nM) |
| 23 |
Bicyclic dihydroindolone pyrrole |
Colo-205 cells |
EC50 1.0 (nM) |
Inhibition of HL-60 and regression of tumors in the promyelocytic leukemia xenograft model |
145
|
| A375 cells |
EC50 2.0 (nM) |
| 24 |
Fused thiophene |
HT-29 pERK |
IC50 6 (nM) |
Inhibition of pERK in the HT-29 tumor |
146
|
| HT-29 |
IC50 79 (nM) |
| 25 |
3-Benzylcoumarins |
HEK293 cell line |
EC50 19.38 (μM) |
Inhibited virus (EV71) replication in HEK293 and RD cells |
147
|
| CC50 65.31 (μM) |
| TI (CC50/IC50) 3.37 (μM) |
| RD cell line |
EC50 10 (μM) |
| CC50 72.92 (μM) |
| TI (CC50/IC50) 7.29 (μM) |
| 26 |
Propoxybenzamide |
A375 cell line |
IC50 0.0176 (μM) |
Inhibited DNA replication of A375 cells |
148
|
| 27 |
Benzothiazole-pyrrole |
MCF-7 cells |
GI50 0.92 ± 0.04 (μM) |
Stopped G1 phase cells, signifying the G2/M cell cycle |
149
|
| MDA-MB231 cells |
GI50 1.76 ± 0.352 (μM) |
| 28 |
Coumarin |
HCT116 cells |
IC50 40 (nM) |
Inhibitory effect on HCT116 cell growth |
150
|
| 29 |
2-(1-Substituted benzyl-1H-tetrazol-5-yl)-3-phenylacrylonitrile |
MCF-7 cells |
IC50 ± 30 (μM) |
The substituted group at the N1 position enhanced the antitumor activity of the parent compound |
151
|
| CaCo2 cells |
IC50 ± 37 (μM) |
| HeLa cells |
IC50 ± 29 (μM) |
| SkBr3 cell line |
IC50 ± 35 (μM) |
| 30 |
3-Benzyl-1,3-benzoxazine-2,4-dione |
CPE cell line |
EC50 1.02 ± 0.085 (μM) |
Suppression of EV71 VPI expression, and an EV71 induced cytopathic effect |
152
|
| 31 |
Thiosemicarbazone |
MDA-MB-231 cells |
IC50 1.9 ± 0.3 (μM ± SEM) |
Demonstrated robust antitumor efficacy correlated with inhibition of MAPK kinase signal transduction |
153
|
| MDA-MB-468 cells |
IC50 2.4 ± 0.2 (μM ± SEM) |
| MCF-7 cells |
IC50 2.1 ± 0.2 (μM ± SEM) |
| BT-474 cells |
IC50 2.6 ± 0.4 (μM ± SEM) |
| SkBr3 cells |
IC50 2.3 ± 0.4 (μM ± SEM) |
| T-47D cell line |
IC50 3.0 ± 0.4 (μM ± SEM) |
| 32 |
N-(Piperazin-1-yl)alkyl-1H-dibenzo[a,c]carbazole |
SMMC-7721 |
IC50 1.39 ± 0.13 (μM) |
Damage the cell membrane's integrity, ultimately causing the HeG2 cells to undergo apoptosis and cancer |
154
|
| HepG2 cells |
IC50 0.51 ± 0.09 (μM) |
| Hep3B cells |
IC50 0.73 ± 0.08 (μM) |
| QSG-7701 cells |
IC50 12.52 ± 0.58 (μM) |
| 33 |
Benzoxazole |
A375 cells |
IC50 4.3 ± 0.7 (nM) |
G0/G1 phase cell cycle delay in A375 cells |
100
|
| Colo-205 cells |
IC50 5.7 ± 0.3 (nM) |
| HT-29 cells |
IC50 2.9 ± 0.6 (nM) |
| Calu-6 cells |
IC50 169 ± 97.7 (nM) |
| A431 cells |
IC50 >3000 (nM) |
