Article
Chemistry, Multidisciplinary
Ruxuan Wang, Rentao Zhang, Haoran Yang, Nina Xue, Xiaoguang Chen, Xiaoming Yu
Summary: Heat shock protein 90 (Hsp90) is an attractive target for anticancer drugs, and Geldanamycin (GA) is the first identified Hsp90 inhibitor. However, the toxicity associated with the benzoquinone moiety of GA limits its clinical application. This study aimed to modify the C6-position of GA and evaluated the anticancer activity of the modified compounds. The results showed that the modified compounds exhibited stronger antitumor effects.
CHINESE CHEMICAL LETTERS
(2023)
Article
Chemistry, Organic
Russell R. A. Kitson, Christopher J. Moody
Summary: This paper reports the synthesis of a series of 19-substituted geldanamycin derivatives using optimized synthetic methods. These new compounds are of significant medicinal interest due to their significantly reduced toxicity compared to the unsubstituted counterparts previously evaluated in clinical trials.
Article
Pharmacology & Pharmacy
Jessica R. McCombs, Hsuan Ping Chang, Dhaval K. Shah, Shawn C. Owen
Summary: This study aims to increase the maximum cytotoxicity of ADC treatment by co-delivering a small molecule inhibitor targeting HSP90 along with ADC, which can overcome HER2 endosomal recycling. The pulse treatment regime with GA helps to decrease the amount of ADC required to achieve maximum cytotoxicity while minimizing baseline cytotoxicity. Such co-treatments could offer a viable solution to increase ADC efficacy in hard to treat or resistant HER2-positive cancers.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2021)
Article
Chemistry, Organic
Zhi Zhang, Yunfeng Li, Rentao Zhang, Xiaoming Yu
Summary: The total synthesis of geldanamycin, a well-known polyketide with potent anticancer activity, was completed in 26 linear steps with an overall yield of 2.65%. High convergency was achieved by disconnecting between C12 and C13 to create C5-C12 and C13-C21 fragments, and using an alkynyl ketone as the precursor for the CS-C12 fragment allowed for reagent-controlled establishment of C7 chirality and flexible substituent exchange at C8.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Scott A. Scarneo, Aaron P. Smith, Jacob Favret, Robert O'Connell, Joy Pickeral, Kelly W. Yang, Guido Ferrari, David R. Loiselle, Philip F. Hughes, Manjusha M. Kulkarni, Madhusudhana Gargesha, Bryan Scott, Debashish Roy, Barton F. Haynes, Jesse J. Kwiek, Timothy A. J. Haystead
Summary: Hsp90 has been investigated as a therapeutic target in cancer for over two decades. The membrane expressed form of Hsp90 (mHsp90) plays a crucial role in T cell activation and could be a therapeutic target for chronic diseases like rheumatoid arthritis.
SCIENTIFIC REPORTS
(2022)
Article
Engineering, Biomedical
Kwang Suk Lim, Daniel Y. Lee, Seungmin Han, David A. Bull, Young-Wook Won
Summary: HSP90 is crucial for cancer cell survival, and incorporating HSP90 inhibitors into antibodies through biological affinity binding can enhance targeted delivery and improve anti-cancer efficacy.
Review
Pharmacology & Pharmacy
Megha Yadav, Ankit Kumar Singh, Adarsh Kumar, Suresh Thareja, Pradeep Kumar
Summary: Heat shock protein 90 (Hsp90) is a chaperone protein that plays important roles in various proteins and signaling pathways. Its functions are not limited to cancer but also extend to other diseases. This review provides a compilation of the pharmacological profile of Hsp90 inhibitors, associated problems, and suggested remedies.
CURRENT PHARMACEUTICAL DESIGN
(2022)
Article
Oncology
Behnoush Khaledian, Ayumu Taguchi, Kazuo Shin-ya, Lisa Kondo-Ida, Noritaka Kagaya, Motoshi Suzuki, Taisuke Kajino, Tomoya Yamaguchi, Yukako Shimada, Takashi Takahashi
Summary: The study identified geldanamycin as a potential inhibitor of ROR1 by destabilizing and degrading its protein expression through the ubiquitin/proteasome pathway, leading to a significant suppression of cell proliferation in lung adenocarcinoma cell lines. This suggests that HSP90 inhibition could be a promising therapeutic strategy in ROR1-positive lung adenocarcinoma.
Article
Biochemistry & Molecular Biology
Akshaya Murugesan, Saravanan Konda Mani, Ramesh Thiyagarajan, Suresh Palanivel, Atash V. Gurbanov, Fedor I. Zubkov, Meenakshisundaram Kandhavelu
Summary: This study synthesized several benzenesulfonamide derivatives and evaluated their inhibitory activities on TrkA in GBM cells. The compound AL106 was identified as a potential anti-GBM compound with lower toxicity in non-cancer cells compared to cisplatin. Docking analysis showed that AL106 has good interactions with TrkA.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Qiuyue Zhang, Xuexuan Wu, Jianrui Zhou, Lixiao Zhang, Xiaoli Xu, Lianshan Zhang, Qidong You, Lei Wang
Summary: The HSP90-CDC37 protein-protein interaction system is crucial for kinase maturation and targeting this interaction has emerged as a promising strategy for cancer therapy. By studying inhibitors, a key hydrophobic pocket was identified, leading to the design of an optimum compound DDO-5994 with improved binding affinity and antiproliferative activity.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Subhabrata Chaudhury, Penchala Narasimharao Meka, Monimoy Banerjee, Caitlin N. Kent, Brian S. J. Blagg
Summary: Hsp90 is responsible for folding and trafficking proteins associated with cancer progression. Existing inhibitors have undesired effects, leading to the development of isoform-selective inhibitors. Research shows that Hsp90 beta-selective inhibitors can overcome the detriments of pan-inhibition of Hsp90.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Zhiran Ju, Wei Zhou, Hattan A. Alharbi, Daniel C. Howell, Taifo Mahmud
Summary: Filamentous soil bacteria are known to produce diverse specialized metabolites, with potential pharmaceutical applications. Inactivation of biosynthetic pathways in Streptomyces pactum ATCC 27456 leads to increased production of specific metabolites, such as piericidins and conglobatin. The identification of new conglobatin analogues with altered polyketide backbones, particularly conglobatin F2, shows enhanced antitumor activity and inhibition of colony formation of cancer cells. Further molecular modeling studies reveal the mechanism of action of these metabolites against heat-shock proteins in cancer cells.
ACS CHEMICAL BIOLOGY
(2021)
Article
Biochemical Research Methods
Kejun Yin, Ronghu Wu
Summary: Heat shock protein 90 (HSP90) is a crucial chaperone in human cells and inhibiting its function shows promise for cancer therapy. However, the development of HSP90 inhibitors has been hindered by unexpected toxicity and side effects. To gain a better understanding of the molecular mechanisms behind these issues, a comprehensive investigation of cellular response to HSP90 inhibitors is necessary.
MOLECULAR & CELLULAR PROTEOMICS
(2023)
Article
Chemistry, Medicinal
Rui Li, Zherui Zhang, Shuhong Huang, Ke Peng, Hualiang Jiang, Jingshan Shen, Bo Zhang, Xiangrui Jiang
Summary: Niclosamide, an oral anthelmintic drug, has been found to inhibit SARS-CoV-2 virus replication through autophagy induction. However, its high cytotoxicity and poor oral bioavailability limit its application. In this study, 23 niclosamide analogs were designed and synthesized, and compound 21 showed the best anti-SARS-CoV-2 efficacy with lower cytotoxicity and better pharmacokinetics. Prodrugs were also synthesized to improve the pharmacokinetics of compound 21. The antiviral mechanism of compound 21 was found to be related to modulating the autophagy processes in host cells.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Chemistry, Multidisciplinary
Pilar Hoyos, Almudena Perona, Teodora Bavaro, Francesca Berini, Flavia Marinelli, Marco Terreni, Maria J. Hernaiz
Summary: Molecules with carbohydrate moieties play essential roles in fighting bacterial and viral infections, driving the design of new carbohydrate-containing drugs or vaccines. Traditional methods to produce these compounds face challenges, highlighting the importance of finding sustainable production processes.
ACCOUNTS OF CHEMICAL RESEARCH
(2022)
Article
Pharmacology & Pharmacy
Mingquan Sha, Genxiang Mao, Guofu Wang, Yufeng Chen, Xiaojian Wu, Zhen Wang
ACTA PHARMACEUTICA SINICA B
(2015)
Article
Cell Biology
Ming-Quan Sha, Xiao-Li Zhao, Liang Li, Li-Hui Li, Yi Li, Tian-Geng Dong, Wei-Xin Niu, Li-Jun Jia, Rong-Guang Shao, Yong-Su Zhen, Zhen Wang
CELL DEATH & DISEASE
(2016)
Article
Pharmacology & Pharmacy
Xiao-li Zhao, Jin-jing Chen, Shu-yi Si, Lin-feng Chen, Zhen Wang
EUROPEAN JOURNAL OF PHARMACOLOGY
(2018)
Article
Multidisciplinary Sciences
Xiao-li Zhao, Jin-jing Chen, Guo-ning Zhang, Yu-Ccheng Wang, Shu-yi Si, Lin-Feng Chen, Zhen Wang
SCIENTIFIC REPORTS
(2017)
Article
Chemistry, Multidisciplinary
Jia-jia Shen, Yue-chen Zhan, Hui-ying Li, Zhen Wang
ACTA PHARMACOLOGICA SINICA
(2020)
Article
Cell Biology
Shuai Lin, Xiao-li Zhao, Zhen Wang
Summary: TBK1 regulates osteoclast differentiation and function in bone marrow macrophages (BMMs) and RAW264.7 cells by modulating the NF-kappa B, MAPKs, and Akt signaling pathways. It also interacts with TNF receptor-associated factor 6 (TRAF6) to affect OC formation. Targeting TBK1 may be a potential therapeutic strategy for bone-related disorders.
IMMUNOLOGY AND CELL BIOLOGY
(2021)
Article
Endocrinology & Metabolism
Xiaoli Zhao, Shuai Lin, Huiying Li, Shuyi Si, Zhen Wang
Summary: The study shows that MPO plays a protective role in bone turnover by limiting osteoclastogenesis and bone resorption through modulating intracellular H2O2 level.
JOURNAL OF BONE AND MINERAL RESEARCH
(2021)
Article
Cell Biology
Ping Li, Xiongxiong Liu, Ting Zhao, Feifei Li, Qiqi Wang, Pengcheng Zhang, Ryoichi Hirayama, Weiqiang Chen, Xiaodong Jin, Xiaogang Zheng, Zhen Wang, Qiang Li
Summary: Studies on radiation interaction with tumor cells revealed that different degrees of premature senescence and complex cell death modalities were induced by carbon-ion radiation. The involvement of p53 status and p21 in enhancing senescence and inhibiting apoptosis were observed, suggesting potential mechanisms for tumor cells to escape from radiation-induced cytotoxicity.
CELL DEATH DISCOVERY
(2021)
Article
Biochemistry & Molecular Biology
Xiaomin Hu, Ying Wang, Chunyan Zhao, Shufen Li, Xinxin Hu, Xuefu You, Jiajia Shen, Zhen Wang, Bin Hong, Bingya Jiang, Yu Du, Linzhuan Wu
Summary: A group of peptide metabolites called mintaimycins were isolated from Micromonospora sp. C-3509. The structures and stereochemistry of mintaimycins were determined through various methods, and the principal component, mintaimycin A(1), exhibited the biological activity of inducing pre-adipocyte differentiation.
Article
Urology & Nephrology
Huiying Li, Xiaoli Zhao, Liyun Zheng, Xiukun Wang, Shuai Lin, Jiajia Shen, Hangjiang Ren, Yi Li, Qiang Qiu, Zhen Wang
Summary: Research has found that Bruceine A is a protective molecule against diabetic kidney disease, with the ability to inhibit inflammatory signal transduction mediated by galectin-1, providing a novel pharmacological therapeutic approach.
KIDNEY INTERNATIONAL
(2022)
Article
Biochemistry & Molecular Biology
Jiajia Shen, Hang Yang, Xinran Qiao, Yang Chen, Liyun Zheng, Jingyu Lin, Jingyu Lang, Qiang Yu, Zhen Wang
Summary: Tripartite motif 17 (TRIM17) is upregulated in gastric cancer (GC) and promotes cell proliferation and survival by interacting with BAX and inhibiting apoptosis. The overexpression of TRIM17 predicts poor prognosis in GC patients, suggesting that TRIM17 may serve as a potential therapeutic target and prognostic biomarker for GC.
CELL DEATH AND DIFFERENTIATION
(2023)
Article
Biochemistry & Molecular Biology
Xinran Qiao, Jingyu Lin, Jiajia Shen, Yang Chen, Liyun Zheng, Hangjiang Ren, Xiaoli Zhao, Hang Yang, Pengyu Li, Zhen Wang
Summary: FBXO28 is a crucial negative regulator of migration, invasion, and metastasis in HCC. It acts as an E3 ubiquitin ligase by directly binding to SNAI2 and degrading it through the ubiquitin proteasome system. Low FBXO28 or PRKACA expression is associated with poor prognosis in HCC patients.
Article
Oncology
Jiajia Shen, Pengyu Li, Xuejing Shao, Yang Yang, Xiujun Liu, Min Feng, Qiang Yu, Ronggui Hu, Zhen Wang
Article
Biochemistry & Molecular Biology
Xiao-li Zhao, Lin-feng Chen, Zhen Wang
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2017)