(Press-News.org) https://doi.org/10.1016/j.apsb.2025.05.003
This new article publication from Acta Pharmaceutica Sinica B, discusses how a CMD-OPT model enables the discovery of a potent and selective RIPK2 inhibitor as preclinical candidate for the treatment of acute liver injury.
Acute liver injury (ALI) serves as a critical precursor and major etiological factor in the progression and ultimate manifestation of various hepatic disorders. The prevention and treatment of ALI is still a serious global challenge. Given the limited therapeutic options for ALI, exploring novel targeted therapeutic agents becomes imperative. The potential therapeutic efficacy of inhibiting RIPK2 is highlighted, as it may provide significant benefits by attenuating the MAPK pathway and NF-κB signaling. This article proposes a CMD-OPT model, a two-stage molecular optimization tool for the rapid discovery of RIPK2 inhibitors with optimal properties. Compound RP20, which targets the ATP binding site, demonstrated excellent kinase specificity, ideal oral pharmacokinetics, and superior therapeutic effects in a model of APAP-induced ALI, positioning RP20 as a promising preclinical candidate. This marks the first application of RIPK2 inhibitors in ALI treatment, opening a novel therapeutic pathway for clinical applications. These results highlight the efficacy of the CMD-OPT model in producing lead compounds from known active molecules, showcasing its significant potential in drug discovery.
Keywords: CMD-OPT, Acute liver injury, RIPK2 inhibitors, Anti-inflammatory, Drug discovery, Co-crystal, Candidate, Kinase specificity
Graphical Abstract: available at https://ars.els-cdn.com/content/image/1-s2.0-S2211383525003090-ga1_lrg.jpg
RP20, as a promising preclinical RIPK2 inhibitor candidate, exhibited excellent kinase selectivity, perfect oral pharmacokinetics, and high safety. It exhibited better therapeutic effects than N-acetylcysteine and GSK2983559 in APAP-induced ALI model. This represents the inaugural deployment of RIPK2 inhibitors in the treatment of ALI, thereby offering a novel therapeutic avenue for clinical application.
# # # # # #
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/
Editorial Board: https://www.journals.elsevier.com/acta-pharmaceutica-sinica-b/editorial-board
APSB is available on ScienceDirect (https://www.sciencedirect.com/journal/acta-pharmaceutica-sinica-b).
Submissions to APSB may be made using Editorial Manager® (https://www.editorialmanager.com/apsb/default.aspx).
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
# # # # #
Yong Chen, Xue Yuan, Wei Yan, Yurong Zou, Haoche Wei, Yuhan Wei, Minghai Tang, Yulian Chen, Ziyan Ma, Tao Yang, Kongjun Liu, Baojian Xiong, Xiuying Hu, Jianhong Yang, Lijuan Chen, CMD-OPT model enables the discovery of a potent and selective RIPK2 inhibitor as preclinical candidate for the treatment of acute liver injury, Acta Pharmaceutica Sinica B, Volume 15, Issue 7, 2025, Pages 3708-3724, ISSN 2211-3835, https://doi.org/10.1016/j.apsb.2025.05.003
END
https://doi.org/10.1016/j.apsb.2025.05.018
This new article publication from Acta Pharmaceutica Sinica B, discusses how melatonin receptor 1a alleviates sleep fragmentation-aggravated testicular injury in T2DM by suppression of TAB1/TAK1 complex through FGFR1.
A major obstacle in type 2 diabetes mellitus (T2DM) is sleep fragmentation (SF), which negatively affects testicular function. However, the underlying mechanisms remain to be elucidated. This study demonstrated that SF induces testicular damage through a mechanism involving lipid metabolism, ...
https://doi.org/10.1016/j.apsb.2025.05.013
This new article publication from Acta Pharmaceutica Sinica B, discusses how single-cell RNA sequencing reveals that Shen-Bai-Jie-Du decoction retards colorectal tumorigenesis by regulating the TMEM131–TNF signaling pathway-mediated differentiation of immunosuppressive dendritic cells.
Colorectal tumorigenesis generally progresses from adenoma to adenocarcinoma, accompanied by dynamic changes in the tumor microenvironment (TME). A randomized controlled trial has confirmed the efficacy and safety of Shen-Bai-Jie-Du decoction (SBJDD) in preventing colorectal ...
https://www.sciencedirect.com/journal/acta-pharmaceutica-sinica-b/vol/15/issue/7
Acta Pharmaceutica Sinica B (APSB) was founded with the goal of creating a global high-level forum centred around drug discovery and pharmaceutical research/application. APSB was included by Chemical Abstracts in 2011, accepted by PubMed Central in 2015, indexed by Science Citation Index in 2017 and has evolved to become one of the most important international journals in the field of pharmaceutical sciences.
APSB is a monthly journal, in English, which publishes ...
In a first for the field, researchers from The Grainger College of Engineering at the University of Illinois Urbana-Champaign have reported a photopumped lasing from a buried dielectric photonic-crystal surface-emitting laser emitting at room temperature and an eye-safe wavelength. Their findings, published in IEEE Photonics Journal, improve upon current laser design and open new avenues for defense applications.
For decades, the lab of Kent Choquette, professor of electrical and computer engineering, have explored VCSELs, a type of surface-emitting laser used in common technology like smartphones, laser printers, barcode scanners, and even vehicles. But ...
A new study led by investigators from Mass General Brigham trialed stereotactic (targeted) brain-directed radiation in 100 patients with small cell lung cancer and brain metastases, finding they experienced positive outcomes that support use of targeted radiation in the future for such patients. Results are published in the Journal of Clinical Oncology.
“Despite being the historical standard, whole brain radiation might not be necessary for all patients,” said first author Ayal Aizer, MD, MHS, director of Central Nervous System Radiation Oncology at Brigham and Women’s Hospital, a founding member of the ...
https://doi.org/10.1016/j.apsb.2025.04.020
This new article publication from Acta Pharmaceutica Sinica B, discusses a high clinically translatable strategy to anti-aging using hyaluronic acid and silk fibroin co-crosslinked hydrogels as dermal regenerative fillers.
An ideal dermal filler should integrate filling, repair, and anti-aging effects, with immediate tissue augmentation, slow degradation, and progressive stimulation of collagen regeneration. However, commonly used hyaluronic ...
A traditionally overlooked type of RNA plays an important role in promoting resilience to depression—but only in females. According to a new study led by the Icahn School of Medicine at Mount Sinai, researchers have now discovered a novel role this molecule plays in how the female brain makes decisions. The authors revealed brain-region-specific and sex-dependent effects of this biomarker, translated from humans to animals, on how individuals make only certain types of choices. This study uncovered ...
Analyzed 174 donated brains, including from former high school, college football players
Larger studies needed to understand how p-tau relates to aging and the extent to which repetitive impact from contact sport predisposes to p-tau accumulation
Whether such changes cause or are associated with clinical problems during life remains unclear
CHICAGO --- In recent years, some scientists and advocates have warned that playing contact sports like football and hockey may increase the risk of brain diseases like Alzheimer’s disease or chronic traumatic encephalopathy (CTE) due to a buildup of a specific protein in the brain.
But a new ...
An international research team led by Freiburg biologists Dr. Wenjing Qi and Prof. Ralf Baumeister has discovered how the LINE1 retrotransposon exploits a cell protein to become active itself, as occurs in tumours. At the same time, the researchers have also deciphered the cell's appropriate countermeasure to prevent conditions such as tumour formation or chronic inflammation. The results have been published in the journal Nature Communications.
Cellular sleepers
"Sleepers" are the name the Secret Service gives agents who live inconspicuously in ...
LA JOLLA, CA—A new microchip invented by Scripps Research scientists can reveal how a person’s antibodies interact with viruses—using just a drop of blood. The technology offers researchers faster, clearer insights that could help accelerate vaccine development and antibody discovery.
“This lets us take a quick snapshot of antibodies as they are evolving after a vaccine or pathogen exposure,” says Andrew Ward, professor in the Department of Integrative Structural and Computational Biology at Scripps Research and senior author of the new paper published ...
