Table 1.
Summary of targeted G-quadruplex (G4)-preferred ligands that exhibit antitumor activities.
| Ligand a | Target G4 or Gene b | Preferred Target Structure c | Cell Line d | Tumor Type | Effect | Notes | References |
|---|---|---|---|---|---|---|---|
| Ni-P | telomere | hybrid | MDA-MB-231 | breast cancer (adenocarcinoma) | · Caner stem cell-specific apoptosis · Bulk cancer-specific apoptosis and senescence · Negligible cytotoxicity to normal somatic cells |
· Tumor growth suppression in a MDA-MB-231 xenograft model vivo | [82,83] |
| MCF-7 | breast cancer (adenocarcinoma) | ||||||
| IZNP1 | telomere | dimeric G4s | SiHa | squamous cell carcinoma | · Apoptosis · Senescence |
·Telomere dysfunction (DNA damage and telomere uncapping) | [85] |
| TH3 | c-MYC | c-MYC (parallel) | A549 | lung cancer | · Antiproliferative effect (apoptosis) · Negligible cytotoxicity to normal somatic cells |
· Validation of the minimal effects for a G4-driven gene (BCL2) | [97] |
| Hela | cervical cancer | ||||||
| IZCZ-3 | c-MYC | c-MYC (parallel) | SiHa | squamous cell carcinoma | · Antiproliferative effect (apoptosis) · Negligible cytotoxicity to normal somatic cells |
· Validation of c-MYC G4-dependent gene suppression · Tumor growth suppression in a SiHa xenograft model in vivo |
[98] |
| Hela | cervical cancer | ||||||
| Huh7 | liver cancer | ||||||
| A375 | malignant melanoma | ||||||
| Benzofuran derivative | c-MYC | c-MYC (parallel) | L363 MM1S MM1R etc. |
myeloma | · Antiproliferative effect (apoptosis) · Negligible cytotoxicity to normal cells |
· Validation of the minimal effects for other G4-driven genes | [102] |
| Tz 1 | c-MYC | c-MYC (parallel) | HCT116 | colorectal carcinoma | · Apoptosis | · Validation of c-MYC G4-dependent gene suppression | [103] |
| Furopyridazinone derivative |
BCL2 | BCL2 (hybrid) | Jurkat | human acute T cell leukemia | · Antiproliferative effect (apoptosis) · Negligible cytotoxicity to normal cells |
- | [135] |
| GTC365 | hTERT | hTERT (stem-loop-containing hybrid) |
MCF-7 | breast cancer (adenocarcinoma) | · Apoptosis · Senescence |
· Validation of decreased telomerase activity and telomere length | [172] |
a This column describes G-quadruplex (G4)-interacting ligands that were reported to exhibit antitumor activities likely based on the clear selectivity to target G4s. b This column a G4-related genomic structure (telomere) or G4-driven genes the were intended to be targeted by each ligand. c This column describes G4 structures or topologies that were preferred by each ligand among other G4s examined in the respective papers. d This column describes cell lines in which antitumor activities of ligands were examined.