ArticleMolecular cancer therapeutics2011
The multitargeted receptor tyrosine kinase inhibitor linifanib (ABT-869) induces apoptosis through an Akt and glycogen synthase kinase 3β-dependent pathway.
Article in Molecular cancer therapeutics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 28 citations in OpenAlex.
- Recent Progress in Urea-Containing Compounds as Tyrosine Kinase Inhibitors.Chemistry & biodiversity · 2026Review
- Apoptotic effect of linifanib on human ovarian cancer OVCAR3 cell line.Research in pharmaceutical sciences · 2025Article
- Comprehensive characterization of respiratory genes based on a computational framework in pan-cancer to develop stratified treatment strategies.PLoS computational biology · 2025Article
- A novel molecular classification based on efferocytosis-related genes for predicting clinical outcome and treatment response in acute myeloid leukemia.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Article
- Synergistic activity of linifanib and irinotecan increases the survival of mice bearing orthotopically implanted human anaplastic thyroid cancer.American journal of cancer research · 2020Article
- Patients with FLT3-mutant AML needed to enroll on FLT3-targeted therapeutic clinical trials.Blood advances · 2019Article
- The role of exosomes and MYC in therapy resistance of acute myeloid leukemia: Challenges and opportunities.Molecular aspects of medicine · 2019Review
- Design and Discovery of Quinazoline- and Thiourea-Containing Sorafenib Analogs as EGFR and VEGFR-2 Dual TK Inhibitors.Molecules (Basel, Switzerland) · 2017Article
- Radiolabeled cyclic RGD peptides as radiotracers for tumor imaging.Biophysics reports · 2016Review
- Radiolabeled Cyclic RGD Peptide Bioconjugates as Radiotracers Targeting Multiple Integrins.Bioconjugate chemistry · 2015Review
- Monitoring tumor response to linifanib therapy with SPECT/CT using the integrin αvβ3-targeted radiotracer 99mTc-3P-RGD2.The Journal of pharmacology and experimental therapeutics · 2013Article
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
The FMS-like receptor tyrosine kinase 3 (FLT3) plays an important role in controlling differentiation and proliferation of hematopoietic cells. Activating mutations in FLT3 occur in patients with acute myeloid leukemia (AML; 15%-35%), resulting in abnormal cell proliferation. Furthermore, both adult and pediatric patients with AML harboring the FLT3 internal tandem duplication (ITD) mutation have a poor prognosis. Several inhibitors have been developed to target mutant FLT3 for the treatment of AML, yet the molecular pathways affected by drug inhibition of the mutated FLT3 receptor alone have not been characterized as yet. Linifanib (ABT-869) is a multitargeted tyrosine kinase receptor inhibitor that suppresses FLT3 signaling. In this article, we show that treatment with linifanib inhibits proliferation and induces apoptosis in ITD mutant cells in vitro and in vivo. We show that treatment with linifanib reduces phosphorylation of Akt and glycogen synthase kinase 3β (GSK3β). In addition, we show that inhibition of GSK3β decreases linifanib-induced apoptosis. This study shows the importance of GSK3 as a potential target for AML therapy, particularly in patients with FLT3 ITD mutations.
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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.