ArticleBiochemical pharmacology2024
Enhancing anti-AML activity of venetoclax by isoflavone ME-344 through suppression of OXPHOS and/or purine biosynthesis in vitro.
Article in Biochemical pharmacology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 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
14 citing papers in PubMed, 18 citations in OpenAlex.
- Review
- Genes-first and phenotypes-first paths to treatment resistance in hematological malignancies.Cell death & disease · 2025Review
- Targeting the BCL2 Family: Advances and Challenges in BH3 Mimetic-Based Therapies.International journal of molecular sciences · 2025Review
- Integrating multi-omics approaches in acute myeloid leukemia (AML): Advancements and clinical implications.Clinical and experimental medicine · 2025Review
- Inhibition of Purine Metabolism Promotes the Differentiation of Neuroblastoma Driven by MYCN.Cancer medicine · 2025Article
- Acute myeloid leukemia mitochondria hydrolyze ATP to support oxidative metabolism and resist chemotherapy.Science advances · 2025Article
- Heme promotes venetoclax resistance in multiple myeloma through MEK-ERK signaling and purine biosynthesis.Blood · 2025Article
- Review
- ONC213: a novel strategy to resensitize resistant AML cells to venetoclax through induction of mitochondrial stress.Journal of experimental & clinical cancer research : CR · 2025Article
- Targeting ribonucleotide reductase to enhance the antileukemic activity of gilteritinib against chemoresistantASPET discovery · 2025Article
- Feasibility and Safety of Targeting Mitochondria Function and Metabolism in Acute Myeloid Leukemia.Current pharmacology reports · 2024Article
- The Interplay between Autophagy and Mitochondria in Cancer.International journal of molecular sciences · 2024Review
- Venetoclax: a new player in the treatment of children with high-risk myeloid malignancies?Blood advances · 2024Review
- CanPharmaceuticals (Basel, Switzerland) · 2024Review
Corrections and comments
- Update of
Authors and funding
29 authors at 5 institutions in 1 country.
Funding
Abstract
Venetoclax (VEN), in combination with low dose cytarabine (AraC) or a hypomethylating agent, is FDA approved to treat acute myeloid leukemia (AML) in patients who are over the age of 75 or cannot tolerate standard chemotherapy. Despite high response rates to these therapies, most patients succumb to the disease due to relapse and/or drug resistance, providing an unmet clinical need for novel therapies to improve AML patient survival. ME-344 is a potent isoflavone with demonstrated inhibitory activity toward oxidative phosphorylation (OXPHOS) and clinical activity in solid tumors. Given that OXPHOS inhibition enhances VEN antileukemic activity against AML, we hypothesized that ME-344 could enhance the anti-AML activity of VEN. Here we report that ME-344 enhanced VEN to target AML cell lines and primary patient samples while sparing normal hematopoietic cells. Cooperative suppression of OXPHOS was detected in a subset of AML cell lines and primary patient samples. Metabolomics analysis revealed a significant reduction of purine biosynthesis metabolites by ME-344. Further, lometrexol, a purine biosynthesis inhibitor, synergistically enhanced VEN-induced apoptosis in AML cell lines. Interestingly, AML cells with acquired AraC resistance showed significantly increased purine biosynthesis metabolites and sensitivities to ME-344. Furthermore, synergy between ME-344 and VEN was preserved in these AraC-resistant AML cells. In vivo studies revealed significantly prolonged survival upon combination therapy of ME-344 and VEN in NSGS mice bearing parental or AraC-resistant MV4-11 leukemia compared to the vehicle control. This study demonstrates that ME-344 enhances VEN antileukemic activity against preclinical models of AML by suppressing OXPHOS and/or purine biosynthesis.
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.