ArticleCell chemical biology2019
Small-Molecule-Targeting Hairpin Loop of hTERT Promoter G-Quadruplex Induces Cancer Cell Death.
Article in Cell chemical biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 57 citations in OpenAlex.
- Non-B DNA structures and their contributions to genetic diversity, aging, and disease.Nucleic acids research · 2026Review
- Revealing G4 Structures as Drug Targets: Exploring the Potential of Novel Therapeutic Agents.Research (Washington, D.C.) · 2026Review
- Leveraging sequences missing from the human genome to diagnose cancer.Communications medicine · 2025Article
- Telomerase in cancer- ongoing quest and future discoveries.Molecular biology reports · 2025Review
- Modulation of dynamic DNA G-quadruplex structures in the hTERT promoter region by ligands.Nucleic acids research · 2024Article
- A Phenotypic Approach to the Discovery of Potent G-Quadruplex Targeted Drugs.Molecules (Basel, Switzerland) · 2024Review
- MicroRNA-21 in urologic cancers: from molecular mechanisms to clinical implications.Frontiers in cell and developmental biology · 2024Review
- G4-DNA formation and chromatin remodelling are interdependent in human cells.Chemical science · 2023Article
- Crystal Structure of an i-Motif from the HRAS Oncogene Promoter.Angewandte Chemie (International ed. in English) · 2023Article
- The Potent G-Quadruplex-Binding Compound QN-302 Downregulates S100P Gene Expression in Cells and in an In Vivo Model of Pancreatic Cancer.Molecules (Basel, Switzerland) · 2023Article
- Higher-order G-quadruplexes in promoters are untapped drug targets.Frontiers in chemistry · 2023Review
- Reactivation of telomerase reverse transcriptase expression in cancer: the role of TERT promoter mutations.Frontiers in cell and developmental biology · 2023Review
- Review
- Emerging mechanisms of telomerase reactivation in cancer.Trends in cancer · 2022Review
- High-throughput techniques enable advances in the roles of DNA and RNA secondary structures in transcriptional and post-transcriptional gene regulation.Genome biology · 2022Review
- High-throughput characterization of the role of non-B DNA motifs on promoter function.Cell genomics · 2022Article
- Rational design of small-molecules to recognize G-quadruplexes of c-MYC promoter and telomere and the evaluation of their in vivo antitumor activity against breast cancer.Nucleic acids research · 2022Article
- Drug discovery of small molecules targeting the higher-order hTERT promoter G-quadruplex.PloS one · 2022Article
- Research Progress on G-Quadruplexes in Human Telomeres and Human Telomerase Reverse Transcriptase (hTERT) Promoter.Oxidative medicine and cellular longevity · 2022Review
- Structured Waters Mediate Small Molecule Binding to G-Quadruplex Nucleic Acids.Pharmaceuticals (Basel, Switzerland) · 2021Article
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9 authors at 1 institution in 1 country.
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Abstract
Increased telomerase activity is associated with malignancy and poor prognosis in human cancer, but the development of targeted agents has not yet provided clinical benefit. Here we report that, instead of targeting the telomerase enzyme directly, small molecules that bind to the G-hairpin of the hTERT G-quadruplex-forming sequence kill selectively malignant cells without altering the function of normal cells. RG260 targets the hTERT G-quadruplex stem-loop folding but not tetrad DNAs, leading to downregulation of hTERT expression. To improve physicochemical and pharmacokinetic properties, we derived a small-molecule analog, RG1603, from the parent compound. RG1603 induces mitochondrial defects including PGC1α and NRF2 inhibition and increases oxidative stress, followed by DNA damage and apoptosis. RG1603 injected as a single agent has tolerable toxicity while achieving strong anticancer efficacy in a tumor xenograft mouse model. These results demonstrate a unique approach to inhibiting the hTERT that functions by impairing mitochondrial activity, inducing cell death.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.