ArticleCell & bioscience2019
Preclinical development of HQP1351, a multikinase inhibitor targeting a broad spectrum of mutant KIT kinases, for the treatment of imatinib-resistant gastrointestinal stromal tumors.
Article in Cell & bioscience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Intrinsic cellular resistance to BCR::ABL1 inhibitors.Haematologica · 2026Review
- Olverembatinib, a novel BCR-ABL tyrosine kinase inhibitor, exhibits anti-tumor activity and synergizes with gemcitabine in pancreatic ductal adenocarcinoma.NPJ precision oncology · 2026Article
- Olverembatinib (HQP1351): a third-generation tyrosine kinase inhibitor in the treatment of hematologic and solid malignancies-a comprehensive review of clinical outcomes.Discover oncology · 2026Review
- Olverembatinib, a multikinase inhibitor that modulates lipid metabolism, in advanced succinate dehydrogenase-deficient gastrointestinal stromal tumors: a phase 1b study and translational research.Signal transduction and targeted therapy · 2025Article
- Olverembatinib in chronic myeloid leukemia-Review of historical development, current status, and future research.Cancer · 2025Review
- Enhancing drug and cell line representations via contrastive learning for improved anti-cancer drug prioritization.NPJ precision oncology · 2024Article
- The Progress of Small Molecule Targeting BCR-ABL in the Treatment of Chronic Myeloid Leukemia.Mini reviews in medicinal chemistry · 2024Review
- Combination venetoclax and olverembatinib (HQP1351) as a successful therapeutic strategy for relapsed/refractory (R/R) mixed-phenotype blast phase of chronic myeloid leukemia.Annals of hematology · 2023Article
- Nintedanib overcomes drug resistance from upregulation of FGFR signalling and imatinib-induced KIT mutations in gastrointestinal stromal tumours.Molecular oncology · 2022Article
- Olverembatinib: First Approval.Drugs · 2022Review
- A review of the therapeutic role of the new third-generation TKI olverembatinib in chronic myeloid leukemia.Frontiers in oncology · 2022Review
- Potential drug-drug interaction of olverembatinib (HQP1351) using physiologically based pharmacokinetic models.Frontiers in pharmacology · 2022Article
- Resistance to Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia-From Molecular Mechanisms to Clinical Relevance.Cancers · 2021Review
- Review of New-Generation Tyrosine Kinase Inhibitors for Chronic Myeloid Leukemia.Current oncology reports · 2021Review
- Chronic myeloid leukemia-from the Philadelphia chromosome to specific target drugs: A literature review.World journal of clinical oncology · 2021Review
- Evaluation of CML TKI Induced Cardiovascular Toxicity and Development of Potential Rescue Strategies in a Zebrafish Model.Frontiers in pharmacology · 2021Article
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Abstract
backgroundImatinib shows limited efficacy in patients with gastrointestinal stromal tumors (GISTs) carrying secondary KIT mutations. HQP1351, an orally bioavailable multikinase BCR-ABL inhibitor, is currently in clinical trials for the treatment of T315I mutant chronic myelogenous leukemia (CML), but the potential application in imatinib-resistant GISTs carrying secondary KIT mutations has not been explored.
methodsThe binding activities of HQP1351 with native or mutant KIT were first analyzed. Imatinib-sensitive GIST T1 and imatinib-resistant GIST 430 cells were employed to test the in vitro antiproliferative activity. Colony formation assay, cell migration assay and cell invasion assay were performed to evaluate the clonogenic, migration and invasion ability respectively. Flow cytometry and western blot analysis were used to detect cell apoptosis, cell cycle and signaling pathway. In vivo antitumor activity was evaluated in mouse xenograft models derived from GIST cell lines.
resultsHQP1351 potently inhibited both wild-type and mutant KIT kinases. In both imatinib-resistant and sensitive GIST cell lines, HQP1351 exhibited more potent or equivalent antiproliferative activity compared with ponatinib, a third generation BCR-ABL and KIT inhibitor. HQP1351 led to more profound inhibition of cell colony formation, cell migration and invasion, cell cycle arrest and cell apoptosis than ponatinib. Furthermore, HQP1351 also inhibited p-KIT, p-AKT, p-ERK1/2, and p-STAT3 to a higher extent than ponatinib. Finally, in xenograft tumor models derived from imatinib-resistant GIST cancer cell lines, HQP1351 exhibited antitumor activity superior to ponatinib.
conclusionsCollectively, our in vitro and in vivo results suggest that the therapeutic application of HQP1351 in imatinib-resistant GIST patients deserves further investigation in clinical trials.
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