(Press-News.org) https://doi.org/10.1016/j.apsb.2025.10.031
This new article publication from Acta Pharmaceutica Sinica B, discusses DHL-11, a novel prieurianin-type limonoid isolated from Munronia henryi, targeting IMPDH2 to inhibit triple-negative breast cancer.
Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, characterized by the poorest prognosis, and poses a significant threat to women's health. In this study two novel prieurianin-type limonoids extracted from Munronia henryi were identified, one of which, named DHL-11, exhibited antitumor activity against TNBC cells. DHL-11 suppressed cell proliferation and migration, induced G2/M cell cycle arrest and apoptosis, and effectively increased the accumulation of reactive oxygen species (ROS) and cellular DNA damage in TNBC cells. Mechanistically, it was found that DHL-11 binds to the non-catalytic pocket of IMPDH2 and disrupts the interaction between IMPDH2 and FANCI, leading to the degradation of the IMPDH2 protein. The decrease of IMPDH2 protein reduced guanine synthesis, increased ROS levels, and induced DNA damage. DHL-11 significantly inhibited the growth of breast cancer patient-derived organoids with high IMPDH2 expression. Furthermore, DHL-11 inhibited the growth and metastasis of TNBC xenografts in vivo with favorable biosafety profiles. These findings highlight the potential of DHL-11 as a novel IMPDH2 degrader for the treatment of IMPDH2-positive TNBC.
Keywords: Limonoids, DHL-11, TNBC, ROS, DNA damage, IMPDH2, Guanine, FANCI
Graphical Abstract: available at https://ars.els-cdn.com/content/image/1-s2.0-S2211383525007099-ga1_lrg.jpg
DHL-11 competes with FANCI to bind IMPDH2, destabilizing it, reducing GMP synthesis, causing DNA damage and replication stress, and inducing TNBC cell apoptosis.
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The Journal of the Institute of Materia Medica, the Chinese Academy of Medical Sciences and the Chinese Pharmaceutical Association.
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CiteScore: 24.3
Impact Factor: 14.6 (Top 6 journal in the category of Pharmacology and pharmacy)
JIF without self-citation: 13.8
ISSN 2211-3835
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Yu Zhu, Zhibi Zhang, Xueqin Dai, Wenjing Liu, Jian Sun, Jialing Liu, Yuxin Zhao, Wenlong Ren, Chenglong Pan, Zhongmei Zhou, Ying Yan, Longlong Zhang, Ceshi Chen, DHL-11, a novel prieurianin-type limonoid isolated from Munronia henryi, targeting IMPDH2 to inhibit triple-negative breast cancer, Acta Pharmaceutica Sinica B, Volume 16, Issue 1, 2026, Pages 287-304, ISSN 2211-3835, https://doi.org/10.1016/j.apsb.2025.10.031
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https://doi.org/10.1016/j.apsb.2025.09.026
This new article publication from Acta Pharmaceutica Sinica B, discusses the discovery of SARS-CoV-2 PLpro inhibitors and RIPK1 inhibitors with synergistic antiviral efficacy in a mouse COVID-19 model.
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https://doi.org/10.1016/j.apsb.2025.11.026
This new article publication from Acta Pharmaceutica Sinica B, discusses how neg-entropy is the true drug target for chronic diseases.
Molecular mechanisms of chronic diseases are complicated, and this impedes drug target identification and subsequent drug discovery. Entropy increase in human body can be considered the root cause of chronic diseases. Accordingly, the inherent neg-entropic mechanisms, for instance the homeostatic mechanisms for metabolism, immunity, self-healing, etc., are true drug targets. Only very few ...
https://doi.org/10.1016/j.apsb.2025.09.037
This new article publication from Acta Pharmaceutica Sinica B, discusses an Oxygen-boosted dual-section microneedle patch for enhanced drug penetration and improved photodynamic and anti-inflammatory therapy in psoriasis.
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https://doi.org/10.1016/j.apsb.2025.10.027
This new article publication from Acta Pharmaceutica Sinica B, discusses how palmitoylation of Tfr1 enhances platelet ferroptosis and liver injury in heat stroke.
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https://doi.org/10.1016/j.apsb.2025.10.028
This new article publication from Acta Pharmaceutica Sinica B, discusses how structure-guided design of picomolar-level macrocyclic TRPC5 channel inhibitors with antidepressant activity.
Recent advances in ion channel structural biology have enhanced structure-based drug design, yet lipid-occupied binding pockets—often large and flat—remain a major hurdle for developing selective small molecules. TRPC5, a brain-enriched channel regulating depression and anxiety, is a promising therapeutic target, but current preclinical candidates suffer from moderate off-target effects. To address ...
https://doi.org/10.1016/j.apsb.2025.11.025
This new article publication from Acta Pharmaceutica Sinica B, discusses therapeutic drug monitoring of biologics in inflammatory bowel disease.
Therapeutic drug monitoring (TDM) has emerged as a valuable tool for optimizing the use of biologics in inflammatory bowel disease (IBD). However, variations in focus, methodology, and recommendations among relevant guidelines and consensuses have contributed to inconsistencies in their quality. This guideline synthesizes current evidence to standardize TDM of biologics in IBD and improve patient ...
A new global review highlights that tackling climate change requires more than funding or innovation alone. Researchers emphasize that meaningful climate action depends on the coordinated integration of financial systems, technological solutions, and governance reforms. The study presents a comprehensive framework designed to help countries, especially developing nations, implement effective and equitable climate strategies.
Climate change is increasingly threatening ecosystems, economies, and human well-being worldwide. ...
Scientists have discovered that cyanobacteria, microscopic organisms best known for driving harmful algal blooms, may play a major role in spreading antibiotic resistance genes in coastal environments. The findings highlight a previously overlooked link between natural nutrient cycling and the global challenge of antibiotic resistance.
Antibiotic resistance genes enable bacteria to survive exposure to antibiotics, posing serious risks to public health, agriculture, and ecosystem stability. While these genes are widely detected in aquatic environments, their biological drivers and ecological roles have remained poorly understood.
In a new study examining ...
Chestnut Hill, Mass. (2/6/2026) – Children across the globe engage in a constellation of behaviors that support cooperation, an action critical to the survival of the human species, a team of Boston College researchers report today in the journal Science Advances.
The team from Associate Professor of Psychology Katherine McAuliffe’s Cooperation Lab surveyed children in the urban United States, rural Uganda, Canada, and Peru, and the hunter-horticulturalist indigenous Shuar of Ecuador.
The researchers found there are cross-cultural regularities in some aspects of the development ...
