ArticlePloS one2014
Preclinical evaluation of the novel, orally bioavailable Selective Inhibitor of Nuclear Export (SINE) KPT-335 in spontaneous canine cancer: results of a phase I study.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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
59 citing papers in PubMed, 1 synthesis or guideline pooled it, 101 citations in OpenAlex.
- The Comparative Oncology of Canine Malignant Melanoma in Targeted Therapy: A Systematic Review ofInternational journal of molecular sciences · 2024Pooled it
- Phase II study of the oral selective inhibitor of nuclear export (SINE) KPT-335 (verdinexor) in dogs with lymphoma.BMC veterinary research · 2018Trial
- Selective Inhibition of Nuclear Export With Oral Selinexor for Treatment of Relapsed or Refractory Multiple Myeloma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2018Trial
- Preclinical Evaluation of the Novel BTK Inhibitor Acalabrutinib in Canine Models of B-Cell Non-Hodgkin Lymphoma.PloS one · 2016Trial
- A review of spontaneous bone metastases in domestic and laboratory animals.Journal of bone oncology · 2026Review
- Combination effect of Exportin 1 inhibitor (KPT-335) with doxorubicin or vincristine in canine lymphoma cell lines.The Journal of veterinary medical science · 2026Article
- Screening of the Pandemic Response Box Library Identified CRM1/XPO1 as an Anti-Mammarenavirus Druggable Target.Viruses · 2026Article
- Exportin 1 (XPO1) Expression and Effectiveness of XPO1 Inhibitor Against Canine Lymphoma Cell Lines.Veterinary sciences · 2025Article
- Precision preclinical modeling to advance cancer treatment.Journal of the National Cancer Institute · 2025Review
- Pharmacokinetic evaluation and bioavailability of KPT-335 (Verdinexor) in cats.Frontiers in veterinary science · 2025Article
- Canine organoids: state-of-the-art, translation potential for human medicine and plea for standardization.Frontiers in veterinary science · 2025Review
- Prevention and Potential Treatment Strategies for Respiratory Syncytial Virus.Molecules (Basel, Switzerland) · 2024Review
- Development of a UPLC-MS/MS method for quantifying KPT-335 (Verdinexor) in feline plasma for a study of PK.Frontiers in veterinary science · 2024Article
- Leading the pack: Best practices in comparative canine cancer genomics to inform human oncology.Veterinary and comparative oncology · 2023Review
- Histotripsy Ablation in Preclinical Animal Models of Cancer and Spontaneous Tumors in Veterinary Patients: A Review.IEEE transactions on ultrasonics, ferroelectrics, and frequency control · 2022Review
- Reversible disruption of XPO1-mediated nuclear export inhibits respiratory syncytial virus (RSV) replication.Scientific reports · 2021Article
- XPO1/CRM1 is a promising prognostic indicator for neuroblastoma and represented a therapeutic target by selective inhibitor verdinexor.Journal of experimental & clinical cancer research : CR · 2021Article
- Pharmacokinetics of Selinexor: The First-in-Class Selective Inhibitor of Nuclear Export.Clinical pharmacokinetics · 2021Review
- The selective inhibitor of nuclear export (SINE) verdinexor exhibits biologic activity against canine osteosarcoma cell lines.Veterinary and comparative oncology · 2021Article
- The nuclear export protein XPO1 - from biology to targeted therapy.Nature reviews. Clinical oncology · 2021Review
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundThe purpose of this study was to evaluate the activity of Selective Inhibitors of Nuclear Export (SINE) compounds that inhibit the function of the nuclear export protein Exportin 1 (XPO1/CRM1) against canine tumor cell lines and perform a Phase I clinical trial of KPT-335 in dogs with spontaneous cancer to provide a preliminary assessment of biologic activity and tolerability. METHODS AND
findingsCanine tumor cell lines derived from non-Hodgkin lymphoma (NHL), mast cell tumor, melanoma and osteosarcoma exhibited growth inhibition and apoptosis in response to nanomolar concentrations of SINE compounds; NHL cells were particularly sensitive with IC50 concentrations ranging from 2-42 nM. A Phase I clinical trial of KPT-335 was performed in 17 dogs with NHL (naive or relapsed), mast cell tumor or osteosarcoma. The maximum tolerated dose was 1.75 mg/kg given orally twice/week (Monday/Thursday) although biologic activity was observed at 1 mg/kg. Clinical benefit (CB) including partial response to therapy (PR, n = 2) and stable disease (SD, n = 7) was observed in 9/14 dogs with NHL with a median time to progression (TTP) for responders of 66 days (range 35-256 days). A dose expansion study was performed in 6 dogs with NHL given 1.5 mg/kg KPT-335 Monday/Wednesday/Friday; CB was observed in 4/6 dogs with a median TTP for responders of 83 days (range 35-354 days). Toxicities were primarily gastrointestinal consisting of anorexia, weight loss, vomiting and diarrhea and were manageable with supportive care, dose modulation and administration of low dose prednisone; hepatotoxicity, anorexia and weight loss were the dose limiting toxicities.
conclusionsThis study provides evidence that the novel orally bioavailable XPO1 inhibitor KPT-335 is safe and exhibits activity in a relevant, spontaneous large animal model of cancer. Data from this study provides critical new information that lays the groundwork for evaluation of SINE compounds in human cancer.
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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.