ArticleCancer translational medicine
SKI-178: A Multitargeted Inhibitor of Sphingosine Kinase and Microtubule Dynamics Demonstrating Therapeutic Efficacy in Acute Myeloid Leukemia Models.
Article in Cancer translational medicine. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 29 citations in OpenAlex.
- Microglia-independent rAAV-induced inflammation causes persistent ocular immune dysregulation rescued by S1P receptor modulation.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Acid ceramidase controls proteasome inhibitor resistance and is a novel therapeutic target for the treatment of relapsed/refractory multiple myeloma.Haematologica · 2025Article
- Metabolism in hematology: Technological advances open new perspectives on disease biology and treatment.HemaSphere · 2025Review
- The emerging roles of sphingosine 1-phosphate and SphK1 in cancer resistance: a promising therapeutic target.Cancer cell international · 2024Review
- Fanning the Flames of Endoplasmic Reticulum (ER) Stress: Can Sphingolipid Metabolism Be Targeted to Enhance ER Stress-Associated Immunogenic Cell Death in Cancer?Molecular pharmacology · 2024Review
- Therapeutic Potential of Ceramide in Cancer Treatment.Journal of cancer research and oncobiology · 2024Article
- Integrative roles of sphingosine kinase in liver pathophysiology.Toxicological research · 2023Review
- Targeting SphK1/2 by SKI-178 inhibits prostate cancer cell growth.Cell death & disease · 2023Article
- Advancements on the Multifaceted Roles of Sphingolipids in Hematological Malignancies.International journal of molecular sciences · 2022Review
- Harnessing the power of sphingolipids: Prospects for acute myeloid leukemia.Blood reviews · 2022Review
- Targeting sphingosine kinase 1/2 by a novel dual inhibitor SKI-349 suppresses non-small cell lung cancer cell growth.Cell death & disease · 2022Article
- Ceramide-induced integrated stress response overcomes Bcl-2 inhibitor resistance in acute myeloid leukemia.Blood · 2022Article
- Targeting the Sphingosine Kinase/Sphingosine-1-Phosphate Signaling Axis in Drug Discovery for Cancer Therapy.Cancers · 2021Review
- Therapeutic Potential of SphK1 Inhibitors Based on Abnormal Expression of SphK1 in Inflammatory Immune Related-Diseases.Frontiers in pharmacology · 2021Review
- Development of SKI-349, a dual-targeted inhibitor of sphingosine kinase and microtubule polymerization.Bioorganic & medicinal chemistry letters · 2020Article
- Intimate Relations-Mitochondria and Ageing.International journal of molecular sciences · 2020Review
- Analysis of selective target engagement by small-molecule sphingosine kinase inhibitors using the Cellular Thermal Shift Assay (CETSA).Cancer biology & therapy · 2020Article
- Sphingosine kinase-2 is overexpressed in large granular lymphocyte leukaemia and promotes survival through Mcl-1.British journal of haematology · 2020Article
- Antineoplastic Agents Targeting Sphingolipid Pathways.Frontiers in oncology · 2020Review
- Article
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
Abstract
aimTo further characterize the selectivity, mechanism-of-action and therapeutic efficacy of the novel small molecule inhibitor, SKI-178.
methodsUsing the state-of-the-art Cellular Thermal Shift Assay (CETSA) technique to detect "direct target engagement" of proteins intact cells,
resultsHerein, we demonstrate that SKI-178 directly target engages both Sphingosine Kinase 1 and 2. We also present evidence that, in addition to its actions as a Sphingosine Kinase Inhibitor, SKI-178 functions as a microtubule network disrupting agent both
conclusionSKI-178 is a multi-targeted agent that functions both as an inhibitor of the SphKs as well as a disruptor of the microtubule network. SKI-178 induced apoptosis arises from a synergistic interaction of these two activities. SKI-178 is safe and effective in mouse models of AML, supporting its further development as a multi-targeted anti-cancer therapeutic agent.
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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.