Table 1 Cancer-specific telomerase inhibitors
Inhibitors | level | Preclinical Model | Mechanism | Efficacy/Progress |
|---|---|---|---|---|
BIBR1532 | Preclinical | Multiple cancer cells | Specifically block hTR binding site in hTERT | a. Suppressive cancer cell proliferation; b. Enhance chemoradiotherapy |
Imetelstat (GRN163L) | Clinical | CDX mice models | Directly bind hTR sequence and competitively inhibits telomere binding | a. Inhibit MM/GBM/HCC in preclinical studies; b. Several cancer related clinical studies are ongoing; c. Active clinical performance in Myefibrosis and Myelodysplastic Syndromes |
Sanguinarine chloride (SC) | Preclinical | Multiple cancer cells | Inhibit hTERT/telomerase in a p65-dependent manner | Acute inhibitory effect on telomerase and cancer cell growth |
Epigallocatechin gallate (EGCG) | Preclinical | MCF-7 breast cancers cells and HL60 promyelocytic leukemia cells | Decrease hTERT transcription through epigenetic alterations | a. Inhibit cell growth and induce apoptosis in cancers of dissimilar origins; b. Simpler derivatives including MST-312, MST-295, and MST-199 were examined based on the structure of EGCG to exhibit stronger telomerase inhibitory efficacy |
Quercetin | Preclinical | Multiple cancer cells | Induce cell cycle arrest, inhibit cell migration, colony formation and downregulate hTERT expression. | Arrest the cell cycle and induce cancer cell apoptosis |
PMMB-302 | Preclinical | A549 cells | Inhibit the expression of telomerase core proteins, dyskerin and NHP2, and RNA template. | Exhibit the best antiproliferative activity against the A549 cell line |
RZ-001 | Clinical | liver cancer cells and HCC-bearing mice | Efficiently and specifically target hTERT expression | a. Selectively retard hTERT-positive liver cancers; b. Active clinical performance in HCC and GBM |
Telomelysin (OBP-301) | Clinical | Multiple cancer cells | hTERT promoter enables its replication in hTERT transc ription-driven tissues such as cancer | a. Selectively infect and lyse cancer cells; b. Active clinical performance in Hepatocellular carcinoma combination therapy with ICIs will be the most promising therapeutic strategy |
Telomestatin | Clinical | Multiple cancer cells | Inhibit the telomerase function through stabilizing G4 at the telomeric repeat | a. Induce cancer cell growth inhibition; b. Registered for clinical trials of esophageal cancer, melanoma and HCC; c. Synthetic oxazole telomestatin derivatives have been developed and verified for their therapeutic efficacies in preclinical cancer models |
Pidnarulex (CX-5461) | Clinical | Multiple cancer cells | Inhibit RNA Pol 1, stabilize G4, and inhibit Top2 | Undergoing clinical trials for hematologic cancer patients |