ArticleACS medicinal chemistry letters2014
Hydroxybenzothiophene Ketones Are Efficient Pre-mRNA Splicing Modulators Due to Dual Inhibition of Dyrk1A and Clk1/4.
Article in ACS medicinal chemistry letters, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
12 citing papers in PubMed, 47 citations in OpenAlex.
- Article
- Development of 5-hydroxybenzothiophene derivatives as multi-kinase inhibitors with potential anti-cancer activity.Future medicinal chemistry · 2024Article
- 5-Methoxybenzothiophene-2-Carboxamides as Inhibitors of Clk1/4: Optimization of Selectivity and Cellular Potency.Molecules (Basel, Switzerland) · 2021Article
- Targeting CLK3 inhibits the progression of cholangiocarcinoma by reprogramming nucleotide metabolism.The Journal of experimental medicine · 2020Article
- Mutations in spliceosome genes and therapeutic opportunities in myeloid malignancies.Genes, chromosomes & cancer · 2019Review
- Design and synthesis of conformationally constraint Dyrk1A inhibitors by creating an intramolecular H-bond involving a benzothiazole core.MedChemComm · 2018Article
- Synthesis of Bioactive 2-(Arylamino)thiazolo[5,4-f]-quinazolin-9-ones via the Hügershoff Reaction or Cu- Catalyzed Intramolecular C-S Bond Formation.Molecules (Basel, Switzerland) · 2016Article
- Open PHACTS computational protocols forMedChemComm · 2016Article
- Synthesis of Thiazolo[5,4-f]quinazolin-9(8H)-ones as Multi-Target Directed Ligands of Ser/Thr Kinases.Molecules (Basel, Switzerland) · 2016Article
- DYRK1A, a Dosage-Sensitive Gene Involved in Neurodevelopmental Disorders, Is a Target for Drug Development in Down Syndrome.Frontiers in behavioral neuroscience · 2016Review
- 10-iodo-11H-indolo[3,2-c]quinoline-6-carboxylic acids are selective inhibitors of DYRK1A.Journal of medicinal chemistry · 2015Article
- Selectivity Profiling and Biological Activity of Novel β-Carbolines as Potent and Selective DYRK1 Kinase Inhibitors.PloS one · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dysregulated usage of pre-mRNA splicing sites contributes to the progression of cancer, neurodegenerative diseases, and viral infections. Serine/arginine-rich (SR) proteins play major roles in the splice site recognition and are largely regulated by phosphorylation. This provides an option for the pharmacological correction of aberrant splicing by inhibiting the relevant kinases. Cdc2-like kinases (Clks) and dual specificity tyrosine phosphorylation-regulated kinases (Dyrks) were both reported to phosphorylate numerous SR proteins in vitro and in vivo. In this study, we describe the discovery of new selective dual Clk/Dyrk1A/1B inhibitors, which are able to modulate alternative pre-mRNA splicing of model gene transcripts in cells with submicromolar potencies. The optimization process yielded a dual Clk and Dyrk inhibitor with exceptionally high ligand efficiency. Our results suggested that dual inhibition of both Clk1 and Dyrk1A increased the efficacy of pre-mRNA splicing modulation.
Indexed as
Identifiers
What OpenQuestion holds
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.