ArticleBlood2024
Preclinical efficacy of the potent, selective menin-KMT2A inhibitor JNJ-75276617 (bleximenib) in KMT2A- and NPM1-altered leukemias.
Article in Blood, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 45 papers.
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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.
A Phase 1/2, First-in-Human Study of the Menin-KMT2A (MLL1) Inhibitor Bleximenib in Participants With Acute Leukemia (cAMeLot-1)
A Phase 1b Study of Bleximenib in Combination With AML-Directed Therapies for Participants With Acute Myeloid Leukemia Harboring KMT2A or NPM1 Alterations
Who cites it
45 citing papers in PubMed.
- A phase 1/2 study of DS-1594 menin inhibitor in relapsed/refractory acute leukemias.Journal of hematology & oncology · 2025Trial
- Wired to Survive: How AML Cytogenetics Shape Apoptotic Dependence and Venetoclax Resistance.Genes · 2026Review
- The case for prospective MEN1 surveillance in the era of sequential menin inhibitor therapy.Leukemia · 2026Article
- Menin Inhibitors in Acute Myeloid Leukemia: Clinical Integration, Resistance, and the Path Beyond Monotherapy.Cancers · 2026Review
- Discovery and preclinical activity of the menin-KMT2A inhibitor ziftomenib in acute leukemia models.Blood · 2026Article
- Targeting Menin in T-lineage Acute Lymphoblastic Leukemia.Molecular cancer therapeutics · 2026Article
- Menin inhibitors as a treatment for acute leukemia: from bench to the clinic.Blood neoplasia · 2026Review
- Article
- Combining menin and MEK inhibition to target poor prognosis KMT2A-rearranged RAS pathway-mutant acute myeloid leukemia.Blood advances · 2026Article
- CDK8 Inhibition Releases the Muscle Differentiation Block in Fusion-driven Alveolar Rhabdomyosarcoma.Cancer discovery · 2026Article
- Application of next-generation sequencing in the treatment of myelodysplastic syndrome: from mechanisms to clinical practice.Blood science (Baltimore, Md.) · 2026Review
- Menin Inhibition in Acute Myeloid Leukemia: Rewiring Leukemic Transcriptional Networks.International journal of molecular sciences · 2026Review
- CRISPR base editor screening identifies spectrum of MEN1 mutations impacting menin inhibitors in clinical trials.Nature communications · 2026Article
- Targeting "undruggable" cancer proteins: pharmacological challenges and emerging strategies.Translational cancer research · 2026Review
- Current perspectives on KMT2A fusion proteins and menin inhibition in paediatric acute myeloid leukaemia.The FEBS journal · 2026Review
- The diagnostic potential of nanobodies in acute myeloid leukemia.Molecular biology reports · 2026Review
- Menin Inhibitors: A New Era of Targeted Therapies in Acute Myeloid Leukemia.Current treatment options in oncology · 2026Review
- Outcomes of relapsed or refractory acute myeloid leukemia after menin inhibition failure.Blood advances · 2026Article
- Management of Acute Myeloid Leukemia: A Review.Cancers · 2026Review
- Differentiation Syndrome in Acute Myeloid Leukemia: Molecular Mechanisms, Clinical Spectrum, and Emerging Therapeutic Paradigms.International journal of molecular sciences · 2026Review
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Authors and funding
47 authors.
Funding
Abstract
abstractThe interaction between menin and histone-lysine N-methyltransferase 2A (KMT2A) is a critical dependency for KMT2A- or nucleophosmin 1 (NPM1)-altered leukemias and an emerging opportunity for therapeutic development. JNJ-75276617 (bleximenib) is a novel, orally bioavailable, potent, and selective protein-protein interaction inhibitor of the binding between menin and KMT2A. In KMT2A-rearranged (KMT2A-r) and NPM1-mutant (NPM1c) acute myeloid leukemia (AML) cells, JNJ-75276617 inhibited the association of the menin-KMT2A complex with chromatin at target gene promoters, resulting in reduced expression of several menin-KMT2A target genes, including MEIS1 and FLT3. JNJ-75276617 displayed potent antiproliferative activity across several AML and acute lymphoblastic leukemia (ALL) cell lines and patient samples harboring KMT2A or NPM1 alterations in vitro. In xenograft models of AML and ALL, JNJ-75276617 reduced leukemic burden and provided a significant dose-dependent survival benefit accompanied by expression changes of menin-KMT2A target genes. JNJ-75276617 demonstrated synergistic effects with gilteritinib in vitro in AML cells harboring KMT2A-r. JNJ-75276617 further exhibited synergistic effects with venetoclax and azacitidine in AML cells bearing KMT2A-r in vitro, and significantly increased survival in mice. Interestingly, JNJ-75276617 showed potent antiproliferative activity in cell lines engineered with recently discovered mutations (MEN1M327I or MEN1T349M) that developed in patients refractory to the menin-KMT2A inhibitor revumenib. A cocrystal structure of menin in complex with JNJ-75276617 indicates a unique binding mode distinct from other menin-KMT2A inhibitors, including revumenib. JNJ-75276617 is being clinically investigated for acute leukemias harboring KMT2A or NPM1 alterations, as a monotherapy for relapsed/refractory acute leukemia (NCT04811560), or in combination with AML-directed therapies (NCT05453903).
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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.