ArticleProceedings of the National Academy of Sciences of the United States of America2005
Selective modification of alternative splicing by indole derivatives that target serine-arginine-rich protein splicing factors.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 119 citations in OpenAlex.
- Article
- Nonsense-Mediated mRNA Decay: Mechanisms and Recent Implications in Cardiovascular Diseases.Cells · 2025Review
- Review
- SR proteins in cancer: function, regulation, and small inhibitor.Cellular & molecular biology letters · 2024Review
- Small molecules modulating RNA splicing: a review of targets and future perspectives.RSC medicinal chemistry · 2024Review
- Article
- The nexus of long noncoding RNAs, splicing factors, alternative splicing and their modulations.RNA biology · 2024Review
- Towards understandings of serine/arginine-rich splicing factors.Acta pharmaceutica Sinica. B · 2023Review
- Article
- Targeting splicing factors for cancer therapy.RNA (New York, N.Y.) · 2023Article
- SRSF1 acts as an IFN-I-regulated cellular dependency factor decisively affecting HIV-1 post-integration steps.Frontiers in immunology · 2022Article
- The genetics of myelodysplastic syndromes and the opportunities for tailored treatments.Frontiers in oncology · 2022Review
- The role of alternative splicing in human cancer progression.American journal of cancer research · 2021Review
- Emerging Roles of SRSF3 as a Therapeutic Target for Cancer.Frontiers in oncology · 2020Review
- A high-throughput screen identifies small molecule modulators of alternative splicing by targeting RNA G-quadruplexes.Nucleic acids research · 2019Article
- Disruption of RNA Metabolism in Neurological Diseases and Emerging Therapeutic Interventions.Neuron · 2019Review
- The Effects of Opioids on HIV Neuropathogenesis.Frontiers in immunology · 2019Review
- Role of Alternative Splicing in Prostate Cancer Aggressiveness and Drug Resistance in African Americans.Advances in experimental medicine and biology · 2019Review
- Targeting Splicing in Prostate Cancer.International journal of molecular sciences · 2018Review
- Exploiting differential RNA splicing patterns: a potential new group of therapeutic targets in cancer.Expert opinion on therapeutic targets · 2018Review
6 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The prevalence of alternative splicing as a target for alterations leading to human genetic disorders makes it highly relevant for therapy. Here we have used in vitro splicing reactions with different splicing reporter constructs to screen 4,000 chemical compounds for their ability to selectively inhibit spliceosome assembly and splicing. We discovered indole derivatives as potent inhibitors of the splicing reaction. Importantly, compounds of this family specifically inhibit exonic splicing enhancer (ESE)-dependent splicing, because they interact directly and selectively with members of the serine-arginine-rich protein family. Treatment of cells expressing reporter constructs with ESE sequences demonstrated that selected indole derivatives mediate inhibition of ESE usage in vivo and prevent early splicing events required for HIV replication. This discovery opens the exciting possibility of a causal pharmacological treatment of aberrant splicing in human genetic disorders and development of new antiviral therapeutic approaches.
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Registered trials
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.