ArticleBlood cancer journal2022
The PIP4K2 inhibitor THZ-P1-2 exhibits antileukemia activity by disruption of mitochondrial homeostasis and autophagy.
Article in Blood cancer journal, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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
16 citing papers in PubMed.
- Article
- A proximity-labeling map of PI5P4K phosphoinositide kinases interaction networks.The Journal of biological chemistry · 2026Article
- The application of nanotechnology in regulating mitochondrial function in tumor microenvironment for cancer therapy.Theranostics · 2026Review
- Translational investigation of tolinapant (ASTX660) in acute myeloid leukemia by integrating clinical, bioinformatic and pharmacological approaches.Blood research · 2025Article
- Cephalochromin Effects in Triple-Negative Breast Cancer Cells: Apoptosis Induction and Modulation of Survival Pathways.Journal of natural products · 2025Article
- PIP4K2C inhibition reverses autophagic flux impairment induced by SARS-CoV-2.Nature communications · 2025Article
- Phosphoinositide kinases in cancer: from molecular mechanisms to therapeutic opportunities.Nature reviews. Cancer · 2025Review
- Integrating bulk RNA-seq and scRNA-seq data to explore diverse cell death patterns and develop a programmed cell death-related relapse prediction model in pediatric B-ALL.Scientific reports · 2025Article
- Large-scale characterization of drug mechanism of action using proteome-wide thermal shift assays.eLife · 2024Article
- Large-scale characterization of drug mechanism of action using proteome-wide thermal shift assays.bioRxiv : the preprint server for biology · 2024Article
- Pharmacological Inhibition of PIP4K2 Potentiates Venetoclax-Induced Apoptosis in Acute Myeloid Leukemia.International journal of molecular sciences · 2023Article
- The rational design of ARUK2007145, a dual inhibitor of the α and γ isoforms of the lipid kinase phosphatidylinositol 5-phosphate 4-kinase (PI5P4K).RSC medicinal chemistry · 2023Article
- Identification of ARUK2002821 as an isoform-selective PI5P4Kα inhibitor.RSC medicinal chemistry · 2023Article
- The Identification of Potent, Selective, and Brain Penetrant PI5P4Kγ Inhibitors as In Vivo-Ready Tool Molecules.Journal of medicinal chemistry · 2023Article
- Targeting phosphoinositide signaling in cancer: relevant techniques to study lipids and novel avenues for therapeutic intervention.Frontiers in cell and developmental biology · 2023Article
- PIP kinases: A versatile family that demands further therapeutic attention.Advances in biological regulation · 2023Article
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.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The treatment of acute leukemia is challenging because of the genetic heterogeneity between and within patients. Leukemic stem cells (LSCs) are relatively drug-resistant and frequently relapse. Their plasticity and capacity to adapt to extracellular stress, in which mitochondrial metabolism and autophagy play important roles, further complicates treatment. Genetic models of phosphatidylinositol-5-phosphate 4-kinase type 2 protein (PIP4K2s) inhibition have demonstrated the relevance of these enzymes in mitochondrial homeostasis and autophagic flux. Here, we uncovered the cellular and molecular effects of THZ-P1-2, a pan-inhibitor of PIP4K2s, in acute leukemia cells. THZ-P1-2 reduced cell viability and induced DNA damage, apoptosis, loss of mitochondrial membrane potential, and the accumulation of acidic vesicular organelles. Protein expression analysis revealed that THZ-P1-2 impaired autophagic flux. In addition, THZ-P1-2 induced cell differentiation and showed synergistic effects with venetoclax. In primary leukemia cells, LC-MS/MS-based proteome analysis revealed that sensitivity to THZ-P1-2 is associated with mitochondrial metabolism, cell cycle, cell-of-origin (hematopoietic stem cell and myeloid progenitor), and the TP53 pathway. The minimal effects of THZ-P1-2 observed in healthy CD34
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.