ArticleJournal of hematology & oncology2020
Preclinical efficacy for a novel tyrosine kinase inhibitor, ArQule 531 against acute myeloid leukemia.
Article in Journal of hematology & oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
13 citing papers in PubMed, 20 citations in OpenAlex.
- Combined cellular and biochemical profiling of Bruton's tyrosine kinase inhibitor nemtabrutinib reveals potential application in MAPK-driven cancers.Frontiers in oncology · 2025Article
- Pyrimidine depletion enhances targeted and immune therapy combinations in acute myeloid leukemia.JCI insight · 2024Article
- Disrupting autophagy inHaematologica · 2023Article
- BTK inhibitors in the treatment of hematological malignancies and inflammatory diseases: mechanisms and clinical studies.Journal of hematology & oncology · 2022Review
- Comparison of inhibitory effects of irreversible and reversible Btk inhibitors on platelet function.EJHaem · 2021Article
- Current and future treatment strategies in chronic lymphocytic leukemia.Journal of hematology & oncology · 2021Review
- Novel agents and regimens for hematological malignancies: recent updates from 2020 ASH annual meeting.Journal of hematology & oncology · 2021Review
- Emerging agents and regimens for AML.Journal of hematology & oncology · 2021Review
- Targeting Bruton tyrosine kinase using non-covalent inhibitors in B cell malignancies.Journal of hematology & oncology · 2021Review
- Review
- Targeting Bcl-2 Proteins in Acute Myeloid Leukemia.Frontiers in oncology · 2020Review
- Recent progress of prognostic biomarkers and risk scoring systems in chronic lymphocytic leukemia.Biomarker research · 2020Review
- High Expression of VAV Gene Family Predicts Poor Prognosis of Acute Myeloid Leukemia.Technology in cancer research & treatmentArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundAcute myeloid leukemia (AML) is the most common type of adult leukemia. Several studies have demonstrated that oncogenesis in AML is enhanced by kinase signaling pathways such as Src family kinases (SFK) including Src and Lyn, spleen tyrosine kinase (SYK), and bruton's tyrosine kinase (BTK). Recently, the multi-kinase inhibitor ArQule 531 (ARQ 531) has demonstrated potent inhibition of SFK and BTK that translated to improved pre-clinical in vivo activity as compared with the irreversible BTK inhibitor ibrutinib in chronic lymphocytic leukemia (CLL) models. Given the superior activity of ARQ 531 in CLL, and recognition that this molecule has a broad kinase inhibition profile, we pursued its application in pre-clinical models of AML.
methodsThe potency of ARQ 531 was examined in vitro using FLT3 wild type and mutated (ITD) AML cell lines and primary samples. The modulation of pro-survival kinases following ARQ 531 treatment was determined using AML cell lines. The effect of SYK expression on ARQ 531 potency was evaluated using a SYK overexpressing cell line (Ba/F3 murine cells) constitutively expressing FLT3-ITD. Finally, the in vivo activity of ARQ 531 was evaluated using MOLM-13 disseminated xenograft model.
resultsOur data demonstrate that ARQ 531 treatment has anti-proliferative activity in vitro and impairs colony formation in AML cell lines and primary AML cells independent of the presence of a FLT3 ITD mutation. We demonstrate decreased phosphorylation of oncogenic kinases targeted by ARQ 531, including SFK (Tyr416), BTK, and fms-related tyrosine kinase 3 (FLT3), ultimately leading to changes in down-stream targets including SYK, STAT5a, and ERK1/2. Based upon in vitro drug synergy data, we examined ARQ 531 in the MOLM-13 AML xenograft model alone and in combination with venetoclax. Despite ARQ 531 having a less favorable pharmacokinetics profile in rodents, we demonstrate modest single agent in vivo activity and synergy with venetoclax.
conclusionsOur data support consideration of the application of ARQ 531 in combination trials for AML targeting higher drug concentrations in vivo.
Indexed as
Identifiers
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.