ArticleInvestigative ophthalmology & visual science2013
Topical antiangiogenic SRPK1 inhibitors reduce choroidal neovascularization in rodent models of exudative AMD.
Article in Investigative ophthalmology & visual science, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 80 citations in OpenAlex.
- SPHINX31 acts as a SRPK1 inhibitor targeting the ATR/DNA-PKcs/CHK1 replicative checkpoint to inhibit cell growth in non-small cell lung cancer.Molecular oncology · 2026Article
- SRPK3 exacerbates cardiac ischemia/reperfusion injury by regulating KLF3-mTOR/P70 S6K-mediated autophagy.Acta pharmacologica Sinica · 2026Article
- From splicing to disease: the crucial role of serine/arginine protein kinases in cellular regulation.Molecular biology reports · 2026Review
- Review
- The Development of Selective Chemical Probes for Serine Arginine Protein Kinase 3.Chemical biology & drug design · 2025Article
- Potential antitumoral effects of SRPK1 inhibition through modulation of VEGF splicing in pituitary somatotroph tumoral cells.Frontiers in endocrinology · 2025Article
- Integration of multi-omics transcriptome-wide analysis for the identification of novel therapeutic drug targets in diabetic retinopathy.Journal of translational medicine · 2024Article
- Design of a covalent protein-protein interaction inhibitor of SRPKs to suppress angiogenesis and invasion of cancer cells.Communications chemistry · 2024Article
- Small molecules modulating RNA splicing: a review of targets and future perspectives.RSC medicinal chemistry · 2024Review
- Serine-arginine protein kinases and their targets in viral infection and their inhibition.Cellular and molecular life sciences : CMLS · 2023Review
- RNA splicing dysregulation and the hallmarks of cancer.Nature reviews. Cancer · 2023Review
- In Vivo Acute Toxicity Studies of Novel Anti-Melanoma Compounds Downregulators of hnRNPH1/H2.Biomolecules · 2023Article
- SPHINX-Based Combination Therapy as a Potential Novel Treatment Strategy for Acute Myeloid Leukaemia.British journal of biomedical science · 2023Article
- Vascular endothelial growth factor isoforms differentially protect neurons against neurotoxic events associated with Alzheimer's disease.Frontiers in molecular neuroscience · 2023Article
- Serine-arginine-rich protein kinase-1 inhibition for the treatment of diabetic retinopathy.American journal of physiology. Heart and circulatory physiology · 2022Article
- Impaired expression of serine/arginine protein kinase 2 (SRPK2) affects melanoma progression.Frontiers in genetics · 2022Article
- Therapeutic Targeting of Alternative Splicing: A New Frontier in Cancer Treatment.Frontiers in oncology · 2022Review
- SRSF protein kinase 1 modulates RAN translation and suppresses CGG repeat toxicity.EMBO molecular medicine · 2021Article
- Protein-Protein Interaction Inhibitor of SRPKs Alters the Splicing Isoforms of VEGF and Inhibits Angiogenesis.iScience · 2021Article
- Biology of the mRNA Splicing Machinery and Its Dysregulation in Cancer Providing Therapeutic Opportunities.International journal of molecular sciences · 2021Review
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
purposeExudative AMD (wet AMD) is treated by monthly injection into the eye of anti-VEGF proteins. VEGF is alternatively spliced to produce numerous isoforms that differ in angiogenic activity. Serine-rich protein kinase-1 (SRPK1) has been identified as a regulator of pro-angiogenic VEGF splicing by phosphorylating serine-rich splicing factor-1 (SRSF1), which binds to VEGF pre-mRNA. We tested the hypothesis that topical (eye drop) SRPK1-selective inhibitors could be generated that reduce pro-angiogenic isoforms, and prevent choroidal neovascularization in vivo.
methodsNovel inhibitors were tested for SRPK inhibition in vitro, pro-angiogenic VEGF production in RPE cells by PCR and ELISA, and for inhibition of choroidal neovascularisation in mice and rats.
resultsA novel disubstituted furan inhibitor was selective for the SRPK family of kinases and reduced expression of pro-angiogenic but not antiangiogenic VEGF isoforms. This inhibitor and previously identified SRPK inhibitors significantly reduced choroidal neovascularisation in vivo. Topical administration of SRPK inhibitors dose-dependently blocked CNV with an EC50 of 9 μM.
conclusionsThese results indicate that novel SRPK1 selective inhibitors could be a potentially novel topical (eye drop) therapeutic for wet AMD.
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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.