ArticleNature medicine2018
H3B-8800, an orally available small-molecule splicing modulator, induces lethality in spliceosome-mutant cancers.
Article in Nature medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 342 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
342 citing papers in PubMed, 1 synthesis or guideline pooled it, 500 citations in OpenAlex.
- Mutational Characteristics of Primary Mucosal Melanoma: A Systematic Review.Molecular diagnosis & therapy · 2022Pooled it
- The SF3b complex in cancer: structural basis, molecular mechanisms, and therapeutic opportunities.Blood advances · 2026Review
- FAM50A promotes esophageal squamous cell carcinoma progression via splicing-dependent oncogenic circSDK1- and DUSP22-mediated MAPK/FAK activation.Cell discovery · 2026Article
- The cellular landscape of druggable RNA-binding proteins.Nature reviews. Drug discovery · 2026Review
- Systems genetics approaches model the heritable architecture of polyendocrine metabolic ovarian syndrome.The Journal of clinical investigation · 2026Article
- Deconvoluting the multi-faceted roles of alternative splicing events in cancer: From underlying mechanisms to innovative therapeutics.Acta pharmaceutica Sinica. B · 2026Review
- TargetingGenes & development · 2026Article
- RNA splicing in health and disease.Molecular biomedicine · 2026Review
- Phase I Study of Rogocekib in Patients with Advanced, Relapsed, or Refractory Malignant Solid Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Inhibition of PRMT5 sensitizes B-cell non-Hodgkin lymphoma cells to both intrinsic and extrinsic apoptotic cell death.Blood neoplasia · 2026Article
- U2 snRNP inhibition hampers pancreatic cancer cell viability by disrupting DNA repair proficiency and mitotic checkpoint integrity.Journal of experimental & clinical cancer research : CR · 2026Article
- Nonsense-Mediated RNA Decay Is a Targetable Vulnerability in Splicing Factor Mutant Myeloid Neoplasms by Enhancing R-Loop Accumulation and DNA Damage.Cancer research · 2026Article
- The splice of life: an isoform-centric view of disease, technology, and therapeutics.The Journal of clinical investigation · 2026Review
- Splicing-associated network PAK1-CLK1/4-SRRM1 is a vulnerability to overcome chemoresistance in human and mouse acute myeloid leukemia.Science translational medicine · 2026Article
- Inhibition of RNA splicing is a novel therapeutic strategy for disruption of nuclear replicating viruses.bioRxiv : the preprint server for biology · 2026Article
- The emerging roles of alternative splicing in modulating tumor immune responses and immunotherapies.Cell death and differentiation · 2026Review
- Unsupervised Deep Representation Learning and Probabilistic Clustering for the Systems-Level Discovery of Germline Mutation Signatures in Pediatric Cancers.Biomedicines · 2026Article
- Review
- Review
- Modulation of splicing factors SF3B1 and SRSF1 by polypurine reverse Hoogsteen hairpins affects the splicing pattern of estrogen receptor α in breast cancer cells.Cancer cell international · 2026Article
282 more citing papers are in PubMed but not listed here.
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Authors and funding
36 authors at 3 institutions in 1 country.
Funding
Abstract
Genomic analyses of cancer have identified recurrent point mutations in the RNA splicing factor-encoding genes SF3B1, U2AF1, and SRSF2 that confer an alteration of function. Cancer cells bearing these mutations are preferentially dependent on wild-type (WT) spliceosome function, but clinically relevant means to therapeutically target the spliceosome do not currently exist. Here we describe an orally available modulator of the SF3b complex, H3B-8800, which potently and preferentially kills spliceosome-mutant epithelial and hematologic tumor cells. These killing effects of H3B-8800 are due to its direct interaction with the SF3b complex, as evidenced by loss of H3B-8800 activity in drug-resistant cells bearing mutations in genes encoding SF3b components. Although H3B-8800 modulates WT and mutant spliceosome activity, the preferential killing of spliceosome-mutant cells is due to retention of short, GC-rich introns, which are enriched for genes encoding spliceosome components. These data demonstrate the therapeutic potential of splicing modulation in spliceosome-mutant cancers.
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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.