ArticleNature cancer2024
BRD-810 is a highly selective MCL1 inhibitor with optimized in vivo clearance and robust efficacy in solid and hematological tumor models.
Article in Nature cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- Docirbrutinib is a pan-mutant BTK inhibitor and inhibits B-cell receptor signaling in chronic lymphocytic leukemia cells in preclinical and early clinical investigations.Blood cancer journal · 2026Trial
- MCL1 Promotes Endothelial Senescence and Atherosclerosis via Glycolytic Reprogramming-Induced H4K12 Lactylation.International journal of molecular sciences · 2026Article
- Repurposing BH3 mimetics to deplete tumour-infiltrating regulatory T cells and enhance anti-tumour immunity in non-small cell lung cancer.Cell death and differentiation · 2026Article
- Dual action of pimozide through lysosome disruption and inhibition of STATs induces apoptosis in chronic lymphocytic leukemia (CLL).Blood advances · 2026Article
- MCL1 inhibition to enhance the efficacy of MYB targeting in pediatric acute myeloid leukemia.Cell death & disease · 2026Article
- Effective delivery of genome editor to cervical cancer targeting Mcl1 for cancer therapy.Cancer gene therapy · 2026Article
- Predictors of response and rational combinations for the novel MCL-1 inhibitor MIK665 in acute myeloid leukemia.Molecular oncology · 2026Article
- Saga of MCL1 inhibitors in multiple myeloma.Biochemical pharmacology · 2026Review
- High-Throughput Strategies for Streamlining Lipid Nanoparticle Development Pipeline.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Targeting the BCL2 Family: Advances and Challenges in BH3 Mimetic-Based Therapies.International journal of molecular sciences · 2025Review
- Review
- Discovery of Macrocyclic Myeloid Cell Leukemia 1 (Mcl-1) Inhibitors that Demonstrate Potent Cellular Efficacy and In Vivo Activity in a Mouse Solid Tumor Xenograft Model.Journal of medicinal chemistry · 2025Article
- Patient-derived tumoroids from CIC::DUX4 rearranged sarcoma identify MCL1 as a therapeutic target.Nature communications · 2025Article
- Article
- CCL2 blockade combined with PD-1/P-selectin immunomodulators impedes breast cancer brain metastasis.Brain : a journal of neurology · 2025Article
- Senolysis by ABT-263 is associated with inherent apoptotic dependence of cancer cells derived from the non-senescent state.Cell death and differentiation · 2025Article
- Article
- Drugging Challenging Cancer Targets Using Fragment-Based Methods.Chemical reviews · 2025Review
- Exploring BCL2 regulation and upstream signaling transduction in venetoclax resistance in multiple myeloma: potential avenues for therapeutic intervention.Blood cancer journal · 2025Article
- Multidimensional, integrative profiling identifies BCL2L1 methylation as a predictor of MCL1 dependency in pediatric malignancies.JCI insight · 2025Article
Corrections and comments
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Authors and funding
23 authors.
Funding
Abstract
The MCL1 gene is frequently amplified in cancer and codes for the antiapoptotic protein myeloid cell leukemia 1 (MCL1), which confers resistance to the current standard of care. Therefore, MCL1 is an attractive anticancer target. Here we describe BRD-810 as a potent and selective MCL1 inhibitor and its key design principle of rapid systemic clearance to potentially minimize area under the curve-driven toxicities associated with MCL1 inhibition. BRD-810 induced rapid cell killing within 4 h in vitro but, in the same 4-h window, had no impact on cell viability or troponin I release in human induced pluripotent stem cell-derived cardiomyocytes, even at suprapharmacologic concentrations. In vivo BRD-810 induced efficacy in xenograft hematological and solid tumor models despite the short residence time of BRD-810 in plasma. In totality, our data support the hypothesis that short-term inhibition of MCL1 with BRD-810 can induce apoptosis in tumor cells while maintaining an acceptable safety profile. We, therefore, intend to advance BRD-810 to clinical trials.
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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.