Chemico-biological interactions最新文献

ADME profile of AP-238 - opioid designer drug (CAS: 140924-11-4): first application of multi-in silico approach methodology for comprehensive prediction of ADME profile (absorption, distribution, metabolism and excretion) important for clinical toxicology and forensic purposes. AP-238--阿片类特制药物（化学文摘社编号：140924-11-4）的 ADME 特征：首次应用多元硅学方法全面预测对临床毒理学和法医学具有重要意义的 ADME 特征（吸收、分布、代谢和排泄）。

Chemico-biological interactions Pub Date : 2025-03-26 DOI: 10.1016/j.cbi.2025.111493

Kamil Jurowski, Alicja Krośniak

{"title":"ADME profile of AP-238 - opioid designer drug (CAS: 140924-11-4): first application of multi-in silico approach methodology for comprehensive prediction of ADME profile (absorption, distribution, metabolism and excretion) important for clinical toxicology and forensic purposes.","authors":"Kamil Jurowski, Alicja Krośniak","doi":"10.1016/j.cbi.2025.111493","DOIUrl":"https://doi.org/10.1016/j.cbi.2025.111493","url":null,"abstract":"AP-238 is a recently emerged opioid designer drug from the cinnamylpiperazine class, raising increasing concern in forensic and clinical toxicology due to its potential for abuse and limited ADME (absorption, distribution, metabolism, and excretion) profile. This study presents the first comprehensive prediction of the ADME parameters for AP-238 using a multi-in silico approach. Multiple in silico methods (SwissADME, ACD/Percepta, pkCSM, ADMETlab 3.0, ADMET Predictor 12.0, Simulation Plus, XenoSite, and DruMAP) were employed to estimate key ADME parameters. Results indicate high gastrointestinal absorption and blood-brain barrier permeability, suggesting strong psychoactive potential. AP-238 exhibits pH-dependent solubility and interacts variably with P-glycoprotein, which may affect its systemic and central nervous system exposure. Distribution modeling revealed moderate to extensive tissue penetration and significant plasma protein binding. Metabolic simulations identified 11 primary metabolites and involvement of major CYP isoforms (including CYP2B6, CYP2C19, CYP2D6, CYP3A4). Excretion predictions suggest a rapid elimination primarily via hepatic routes. This study provides critical pharmacokinetic insight into AP-238, supporting its early toxicological assessment and prioritization for further investigation. The applied in silico strategy demonstrates a rapid, ethical alternative to traditional ADME testing, particularly valuable in the context of novel synthetic opioids.","PeriodicalId":93932,"journal":{"name":"Chemico-biological interactions","volume":" ","pages":"111493"},"PeriodicalIF":0.0,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Copper exposure induces inflammation and PANoptosis through the TLR4/NF-κB signaling pathway, leading to testicular damage and impaired spermatogenesis in Wilson disease. 铜暴露会通过 TLR4/NF-κB 信号通路诱发炎症和 PAN 细胞凋亡，导致威尔逊氏病患者的睾丸损伤和精子发生障碍。

Chemico-biological interactions Pub Date : 2024-06-01 Epub Date: 2024-05-17 DOI: 10.1016/j.cbi.2024.111060

Dan Zhao, Limin Wu, Xinru Fang, Luyao Wang, Qianzhuo Liu, Pengyu Jiang, Zhihui Ji, Nian Zhang, Miaozhu Yin, Hui Han

{"title":"Copper exposure induces inflammation and PANoptosis through the TLR4/NF-κB signaling pathway, leading to testicular damage and impaired spermatogenesis in Wilson disease.","authors":"Dan Zhao, Limin Wu, Xinru Fang, Luyao Wang, Qianzhuo Liu, Pengyu Jiang, Zhihui Ji, Nian Zhang, Miaozhu Yin, Hui Han","doi":"10.1016/j.cbi.2024.111060","DOIUrl":"10.1016/j.cbi.2024.111060","url":null,"abstract":"Copper is a toxic heavy metal that causes various damage when it accumulates in the body beyond the physiological threshold. Wilson disease (WD) is an inherited disorder characterized by impaired copper metabolism. Reproductive damage in male patients with WD is gradually attracting attention. However, the underlying mechanisms of copper toxicity are unclear. In this study, we investigated the role of inflammation and PANoptosis in testicular damage and impaired spermatogenesis caused by copper deposition using the WD model toxic milk (TX) mice. Copper chelator-penicillamine and toll-like receptor 4 (TLR4) inhibitor-eritoran were used to intervene in TX mice in our animal experiment methods. Testis samples were collected from mice for further analysis. The results showed that the morphology and ultrastructure of the testis and epididymis in TX mice were damaged, and the sperm counts decreased significantly. The TLR4/nuclear factor kappa-B (NF-κB) signaling pathway was activated by copper deposition, which led to the upregulation of serum and testicular inflammatory factors in TX mice. Meanwhile, pyroptosis, apoptosis, and necroptosis were significant in the testis of TX mice. Both chelated copper or inhibited TLR4 expression markedly suppressed the TLR4/NF-κB signaling pathway, thereby reducing the expression of inflammatory factors. PANoptosis in the testis of TX mice was also reversed. Our study indicated that pathological copper exposure induces inflammation and PANoptosis through the TLR4/NF-κB signaling pathway, leading to toxic testicular damage and impaired spermatogenesis in WD.","PeriodicalId":93932,"journal":{"name":"Chemico-biological interactions","volume":" ","pages":"111060"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140961149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Elucidating the Molecular Mechanisms of Pterostilbene Against Cervical Cancer Through an Integrated Bioinformatics and Network Pharmacology Approach 通过综合生物信息学和网络药理学方法阐明紫檀芪抗宫颈癌的分子机制

Chemico-biological interactions Pub Date : 2024-05-01 DOI: 10.1016/j.cbi.2024.111058

Xiang Li, Dequan Yu, Qiming Wang, Yating Chen, Hanbing Jiang

引用次数: 0

Assessment of anti-hyperglycemic and anti-hyperlipidemic effects of thiazolidine-2,4-dione derivatives in HFD-STZ diabetic animal model 评估噻唑烷-2,4-二酮衍生物在 HFD-STZ 糖尿病动物模型中的降血糖和降血脂作用

Chemico-biological interactions Pub Date : 2024-02-01 DOI: 10.1016/j.cbi.2024.110902

S. Fettach, Fatima Zahra Thari, Khalid Karrouchi, Laila Benbacer, Learn-Han Lee, Abdelhakim Bouyahya, Y. Cherrah, Hassan Sefrioui, Khalid Bougrin, M. El Abbes Faouzi

引用次数: 0

Loss of VRK1 alters the nuclear phosphoproteome in the DNA damage response to doxorubicin VRK1缺失会改变DNA损伤对多柔比星反应的核磷酸蛋白组

Chemico-biological interactions Pub Date : 2024-02-01 DOI: 10.1016/j.cbi.2024.110908

Elena Navarro-Carrasco, Aurora Campos-Díaz, Eva Monte-Serrano, F. Rolfs, Richard de Goeij-de Haas, T. Pham, S. Piersma, Connie R. Jimenez, Pedro A. Lazo

引用次数: 0

Neurotoxicity of Pyrethroids in exacerbating neurodegenerative diseases: From animals' models to humans’ studies 拟除虫菊酯在加剧神经退行性疾病方面的神经毒性：从动物模型到人体研究

Chemico-biological interactions Pub Date : 2024-02-01 DOI: 10.1016/j.cbi.2024.110911

Rafael Arsuffi-Marcon, Lizandra Gomes Souza, Artur Santos-Miranda, J. Joviano-Santos

引用次数: 0