ArticleLeukemia2019
Preclinical evaluation of the selective small-molecule UBA1 inhibitor, TAK-243, in acute myeloid leukemia.
Article in Leukemia, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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.
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Who cites it
58 citing papers in PubMed, 87 citations in OpenAlex.
- Chemogenetic ubiquitin E1 inhibitor TAK-243 CRISPR screen uncovers HAPSTR1/HUWE1 axis in chromatin proteostasis and cell cycle control.Science advances · 2026Article
- The ubiquitin-activating enzyme inhibitor TAK-243 activates store-operated CaBiochimica et biophysica acta. Molecular cell research · 2026Article
- Two Mechanisms One Molecule: Developing a 'Truly' Bifunctional Degrader Targeting Rpn13 and CRBN.Journal of the American Chemical Society · 2026Article
- UBA1 drives cell cycle to promote malignancy and serves as a therapeutic target in Ewing Sarcoma.BMC cancer · 2026Article
- CDH4/UBA1/RBMX axis promotes polycystic ovary syndrome progression through YAP1 activation.Cellular & molecular biology letters · 2026Article
- Ubiquitin System-Driven Proteostasis in DNA Damage Response.International journal of molecular sciences · 2026Review
- UBA1 promotes cardiac hypertrophy by suppressing autophagy via targeting ATG5 for ubiquitination.Cell communication and signaling : CCS · 2026Article
- RAS-GTP Inhibition Overcomes Acquired Resistance to KRASG12C Inhibitors Mediated by Oncogenic and Wild-Type RAS Activation in Non-Small Cell Lung Cancer.Cancer research · 2026Article
- UBA1 as a proteostasis-innate immunity checkpoint: lessons from vexas syndrome and therapeutic implications.Frontiers in immunology · 2026Review
- PARylation-centric crosstalk: orchestrating immune evasion and multidrug resistance in ovarian cancer.Frontiers in immunology · 2026Review
- Multidimensional analysis of deubiquitinating enzymes in colorectal cancer: biological mechanisms and targeted therapeutic strategies.Frontiers in oncology · 2026Review
- Distinct characteristics of VEXAS-causative UBA1 M41 and recurrent functional non-M41 mutations.Leukemia · 2025Article
- SF3B1-mutant models of RNA mis-splicing uncover UBA1 as a therapeutic target in myelodysplastic neoplasms.Leukemia · 2025Article
- Targeting proteostasis for cancer therapy: current advances, challenges, and future perspectives.Molecular cancer · 2025Review
- MAGL targeted PROTAC degrader simultaneously enhances P53 for synergistic treatment of glioblastoma stem cell.Cell death discovery · 2025Article
- The UBA1-STUB1 Axis Mediates Cancer Immune Escape and Resistance to Checkpoint Blockade.Cancer discovery · 2025Article
- Ubiquitination Enzymes in Cancer, Cancer Immune Evasion, and Potential Therapeutic Opportunities.Cells · 2025Review
- Inhibiting the RNA helicase DDX3X in Burkitt lymphoma induces oxydative stress and impedes tumor progression in xenografts.Frontiers in cell and developmental biology · 2025Article
- Ubiquitin-Activating Enzyme E1 (UBA1) as a Prognostic Biomarker and Therapeutic Target in Breast Cancer: Insights into Immune Infiltration and Functional Implications.International journal of molecular sciences · 2024Article
- USP24 promotes autophagy-dependent ferroptosis in hepatocellular carcinoma by reducing the K48-linked ubiquitination of Beclin1.Communications biology · 2024Article
Corrections and comments
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Authors and funding
21 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acute myeloid leukemia (AML) is an aggressive hematologic malignancy for which new therapeutic approaches are required. One such potential therapeutic strategy is to target the ubiquitin-like modifier-activating enzyme 1 (UBA1), the initiating enzyme in the ubiquitylation cascade in which proteins are tagged with ubiquitin moieties to regulate their degradation or function. Here, we evaluated TAK-243, a first-in-class UBA1 inhibitor, in preclinical models of AML. In AML cell lines and primary AML samples, TAK-243 induced cell death and inhibited clonogenic growth. In contrast, normal hematopoietic progenitor cells were more resistant. TAK-243 preferentially bound to UBA1 over the related E1 enzymes UBA2, UBA3, and UBA6 in intact AML cells. Inhibition of UBA1 with TAK-243 decreased levels of ubiquitylated proteins, increased markers of proteotoxic stress and DNA damage stress. In vivo, TAK-243 reduced leukemic burden and targeted leukemic stem cells without evidence of toxicity. Finally, we selected populations of AML cells resistant to TAK-243 and identified missense mutations in the adenylation domain of UBA1. Thus, our data demonstrate that TAK-243 targets AML cells and stem cells and support a clinical trial of TAK-243 in this patient population. Moreover, we provide insight into potential mechanisms of acquired resistance to UBA1 inhibitors.
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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.