ArticleRSC chemical biology2020
Structural and biophysical insights into the mode of covalent binding of rationally designed potent BMX inhibitors.
Article in RSC chemical biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 11 citations in OpenAlex.
- Targeting the BMX in cancer: molecular mechanisms and emerging therapeutic strategies.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- Bone marrow kinase X-linked in pulmonary diseases: pathogenic gene, diagnostic biomarker, and treatment target-a narrative review.Translational pediatrics · 2026Review
- Riding toward Selectivity: Optimization of Covalent 7-Azaindole-Based BMX Kinase Inhibitors.Journal of medicinal chemistry · 2026Article
- Inhibition of tyrosine kinase BMX increases cell death in response to existing chemotherapeutic agents overcoming apoptotic resistance in cancer.Cell death & disease · 2025Article
- Preclinical spheroid models identify BMX as a therapeutic target for metastatic MYCN nonamplified neuroblastoma.JCI insight · 2024Article
- BMX controls 3βHSD1 and sex steroid biosynthesis in cancer.The Journal of clinical investigation · 2023Article
- Selective Inhibition of Bruton's Tyrosine Kinase by a Designed Covalent Ligand Leads to Potent Therapeutic Efficacy in Blood Cancers Relative to Clinically Used Inhibitors.ACS pharmacology & translational science · 2022Article
- BMX kinase mediates gilteritinib resistance in FLT3-mutated AML through microenvironmental factors.Blood advances · 2022Article
- Ibrutinib Inhibits BMX-Dependent Endothelial VCAM-1 ExpressionCellular and molecular bioengineering · 2022Article
- 1,6-Naphthyridin-2(1Pharmaceuticals (Basel, Switzerland) · 2021Review
- Discovery of a Novel Class of Covalent Dual Inhibitors Targeting the Protein Kinases BMX and BTK.International journal of molecular sciences · 2020Article
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 5 countries.
Funding
Abstract
The bone marrow tyrosine kinase in chromosome X (BMX) is pursued as a drug target because of its role in various pathophysiological processes. We designed BMX covalent inhibitors with single-digit nanomolar potency with unexploited topological pharmacophore patterns. Importantly, we reveal the first X-ray crystal structure of covalently inhibited BMX at Cys496, which displays key interactions with Lys445, responsible for hampering ATP catalysis and the DFG-out-like motif, typical of an inactive conformation. Molecular dynamic simulations also showed this interaction for two ligand/BMX complexes. Kinome selectivity profiling showed that the most potent compound is the strongest binder, displays intracellular target engagement in BMX-transfected cells with two-digit nanomolar inhibitory potency, and leads to BMX degradation PC3 in cells. The new inhibitors displayed anti-proliferative effects in androgen-receptor positive prostate cancer cells that where further increased when combined with known inhibitors of related signaling pathways, such as PI3K, AKT and Androgen Receptor. We expect these findings to guide development of new selective BMX therapeutic approaches.
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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.