(Press-News.org) https://doi.org/10.1016/j.apsb.2025.10.005
This new article publication from Acta Pharmaceutica Sinica B, discusses the deep learning-based discovery of tetrahydrocarbazoles as broad-spectrum antitumor agents and click-activated strategy for targeted cancer therapy.
Phenotypic screening has played an important role in discovering innovative small-molecule drugs and clinical candidates with unique molecular mechanisms of action. However, conducting cell-based high-throughput screening from vast compound libraries is extremely time-consuming and expensive. Fortunately, deep learning has provided a new paradigm for identifying compounds with specific phenotypic properties. The authors of this article developed a data-driven classification-generation cascade model to discover new chemotype antitumor drugs. Through wet-lab validation, WJ0976 and WJ0909 were identified as tetrahydrocarbazole derivatives and displayed potent broad-spectrum antitumor activity as well as growth inhibitory properties against multidrug-resistant cancer cells. Furthermore, the R-(−)-WJ0909 (WJ0909B), demonstrated optimal antitumor efficacy in vitro and ex vivo patient-derived organoids (PDOs). Further investigations revealed that WJ0909B upregulates p53 expression and cause mitochondria-dependent endogenous apoptosis. Moreover, WJ0909B and the click-activated prodrug WJ0909B-TCO potently inhibited tumor growth in cell-derived xenograft models. This research highlights the significant potential of deep learning-guided approach to phenotypic drug discovery for anticancer drugs and the strategy of click-activated prodrug for targeted cancer therapy.
Keywords: Deep learning, Phenotypic screening, Tetrahydrocarbazoles, Drug delivery, Click-activated prodrug, Antitumor, Drug discovery, p53
Graphical Abstract: available at https://ars.els-cdn.com/content/image/1-s2.0-S2211383525006781-ga1_lrg.jpg
This study established a cascade model by integrating deep learning-driven classifiers and GDL models, identified tetrahydrocarbazole derivatives with subnanomolar activity against pan-cancer cells and patient-derived organoids, and click-activated prodrug strategy showed potent efficacy with minimal toxicity.
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The Journal of the Institute of Materia Medica, the Chinese Academy of Medical Sciences and the Chinese Pharmaceutical Association.
For more information please visit https://www.journals.elsevier.com/acta-pharmaceutica-sinica-b/
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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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Xue Liu, Yalan Lu, Qichen Chen, Minjian Yang, Shize Li, Hanyu Sun, Xiangying Liu, Jingjie Yan, Liangning Li, Nan Xiang, Yan Lu, Qi Geng, Yiqiao Deng, Baolian Wang, Jing Jin, Hong Zhao, Xiandao Pan, Ahmed Al-Harrasi, Tingting Du, Wei Song, Xiaojian Wang, Deep learning-based discovery of tetrahydrocarbazoles as broad-spectrum antitumor agents and click-activated strategy for targeted cancer therapy, Acta Pharmaceutica Sinica B, Volume 16, Issue 1, 2026, Pages 406-422, ISSN 2211-3835, https://doi.org/10.1016/j.apsb.2025.10.005
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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 ...
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.
SARS-CoV-2 continues to propagate globally, posing non-negligible risks of severe COVID-19. Although several clinical antivirals and immunosuppressants offer crucial protection, there is a persistent need for additional therapeutic options to counter emerging viral variants and drug ...
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.
Psoriasis is a prevalent chronic inflammatory skin disorder, characterized by epidermal thickening and an inflammatory hypoxic microenvironment, which significantly hinder drug penetration through the thickened skin and limit the efficacy of photodynamic therapy (PDT). The authors of this article ...
Sepsis is a leading global cause of hospital deaths, occurring when the body’s response to infection damages tissue and causes organs to fail. Africa bears the world’s highest burden of sepsis, with an estimated 48 million cases each year leading to about 11 million deaths. People living with HIV face the greatest risk of dying from the condition.
A new study has found that tuberculosis, a chronic bacterial lung disease, is a major and long-overlooked cause of deadly sepsis among people living with HIV. An associated Phase 3 clinical trial called the ATLAS study found that starting tuberculosis (TB) treatment ...
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.
Heat stroke (HS) is a severe medical emergency characterized by coagulation and high mortality due to organ injury. This study identifies a novel mechanism in which platelet ferroptosis, driven by transferrin receptor 1 (Tfr1) palmitoylation, significantly contributes to liver injury in HS. ...
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 ...
