A analysis workforce led by Prof. Liu Qingsong from the Hefei Institutes of Bodily Science of the Chinese language Academy of Science has developed IHMT-15130, a selective and irreversible inhibitor of Bone marrow kinase in chromosome X (BMX) kinase, which confirmed sturdy efficacy in preclinical fashions of cardiac hypertrophy.
Revealed in ACS Chemical Biology, the research highlights the compound’s twin function in suppressing irritation and reversing pathological coronary heart muscle thickening, positioning it as a promising candidate for treating this main cardiovascular dysfunction.
Cardiac hypertrophy, characterised by irregular coronary heart muscle thickening, is a serious contributor to coronary heart failure, arrhythmias, and cardiovascular mortality. Regardless of its prevalence, therapies focusing on the molecular mechanisms linking irritation to myocardial reworking stay restricted. The X-linked bone marrow tyrosine kinase BMX, a essential endothelial signaling regulator, has emerged as a validated goal because of its aberrant activation in pro-inflammatory pathways underlying hypertrophy.
IHMT-15130 covalently binds to the cysteine 496 residue (Cys496) in BMX kinase’s energetic website, reaching nanomolar efficiency (IC50 = 11.9 nM). Not like twin BTK/BMX inhibitors, it displays >2,000-fold selectivity for BMX over CSK kinase (IC50 > 25,000 nM), drastically lowering dangers of atrial fibrillation and bleeding related to off-target CSK inhibition. This selectivity represents a serious development in focused kinase remedy.
In vitro research confirmed IHMT-15130 potently suppresses pro-inflammatory cytokine manufacturing (TNF-α, IL-6) and inhibits NF-κB signaling in endothelial cells. In angiotensin II-induced mouse fashions, the compound considerably diminished left ventricular hypertrophy with no noticed toxicity. These findings validate its twin mechanism—addressing each irritation and myocardial reworking—and spotlight its therapeutic translational potential.
“This selective inhibitor overcomes limitations of broad-spectrum kinase medicine, providing a safer therapeutic window for inflammation-driven cardiac hypertrophy,” famous Prof. Liu.
Extra data:
Shuang Qi et al, Discovery of IHMT-15130 as a Extremely Potent Irreversible BMX Inhibitor for the Remedy of Myocardial Hypertrophy and Transforming, ACS Chemical Biology (2025). DOI: 10.1021/acschembio.4c00875
Quotation:
Drug candidate IHMT-15130 exhibits twin motion in opposition to coronary heart muscle thickening and irritation (2025, July 9)
retrieved 9 July 2025
from https://medicalxpress.com/information/2025-07-drug-candidate-ihmt-dual-action.html
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