Table 1.

Effects of selected G4 ligands in in-vitro and in-vivo cancer models. Structures are depicted in Figure 4.

G4 Ligand (Chemotype)	Target in Cancer Cells	Effects	Refs.
BRACO-19 (acridine)	Telomere G4 in glioblastoma cells	Induces telomere uncapping; inhibits telomerase activity; induces DNA damage, apoptosis and senescence.	[79]
RHSP4 (acridinium)	Telomere G4 in glioblastoma cells	Radiosensitizing agent in a glioblastoma multiforme xenograft model, inducing telomere dysfunction.	[80]
SchCoD (quinazolinone)	Telomere G4 in cervical squamous cancer	It induces telomere uncapping, leading to a DNA damage response and inhibits tumor growth in a xenograft model.	[81]
QN-1 (quinoxaline)	c-MYC promoter G4 in triple-negative breast cancer	Downregulation of c-MYC transcription in vitro and in vivo. Anticancer activity in a xenograft model.	[88]
APTO-253 (phenanthroline)	c-MYC promoter G4 in acute myeloid leukemia	Inhibits c-Myc expression, induces cell cycle arrest and apoptosis in acute myeloid leukemia cells; induces the Krüppel-like factor 4 (KLF4) tumor suppressor.	[89,90]
		In Phase I clinical trials.	[97]
IQb2 (indoloquinoline)	k-RAS promoter G4 in colon cancer cells	Decrease wild-type k-RAS promoter activity; preferentially downregulation of k-RAS expression compared to other G4-containing genes; induces apoptosis and expression of tumor suppressor p53 in HCT116 cell line.	[94]
GTC365 (acridine)	hTERT promoter G4 in breast cancer cells	Binds to G-quartet and duplex stem loop of G4, restoring wild-type folding topology; Induces apoptosis and senescence in cancer cells.	[95]
TA20 (triarylpyridine)	Several DNA G4 in cervical cancer cells	Stabilizes several G4s in vitro. Transcriptome analysis of treated cancer cells revealed that most affected genes are those related with DNA damage, cell growth and autophagy; genes enriched in G4-forming sequences are preferentially downregulated.	[93]
CM03 (naphthalene diimide)	Several DNA G4 in pancreatic cancer	Stabilizes several G4s in vitro and increases G4 foci in treated cells; Transcriptome analysis indicates a preferential downregulation of genes with G4-forming sequences in promoters and implicated in cancer cells survival, development of metastasis and drug resistance; Anticancer activity in a xenograft model.	[92]
RGB-1 (thienopyrimidinone)	5′-UTR G4 of NRAS mRNA in breast cancer	Downregulation of NRAS expression in cancer cell lines.	[77]
Quarfloxin/CX-3543 (quinolone)	Ribosomal DNA G4 in Carcinoid/neuroendocrine tumors	Inhibits rRNA biogenesis; induces DNA damage and apoptosis.	[98]
		Reached Phase II clinical trials.	[99]
CX-5461 (quinolone)	Ribosomal DNA G4 in BRCA1/2-deficient tumors	Inhibits RNA polymerase I and Topoisomerase II.	[100,101]
		Induces G4-mediated DNA damage.	[102]
		In Phase I Clinical trials.	[103]