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
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
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, Medicinal
Meng Li, Xianlan She, Yufei Ou, Jiangxin Liu, Zaifeng Yuan, Qin-shi Zhao
Summary: Hsp90 is an ATP-dependent chaperone that plays a crucial role in protein assembly and folding. It has been found to be involved in cancer, viral infection, neurodegenerative disease, and inflammation. In this study, a series of novel analogues were designed, synthesized, and evaluated for their inhibitory activity against Hsp90. Among these analogues, compound 29 and 31 showed the most potent inhibitory activity. Mechanism studies revealed that compound 29 promoted cell apoptosis through the mitochondrial-mediated pathway. Furthermore, compound 29 exhibited anti-tumor activity in a mouse model and showed low acute toxicity. These findings suggest that compound 29 has potential for further development as a therapeutic agent.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
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.
Article
Chemistry, Medicinal
Laura Grau, Richard Soucek, M. Dolors Pujol
Summary: Resveratrol, a natural compound with antioxidant properties, has potential as both a chemopreventive and cancer chemotherapeutic agent. Due to its poor bioavailability, the study of new derivatives is important. In this study, (E)-stilbenes derived from resveratrol and cyclic analogues with benzofuran or indole nucleus were synthesized and evaluated for their impact on tumor growth. Some compounds showed higher cytotoxicity than (E)-resveratrol, with one derivative demonstrating eight times greater cytotoxic activity against colon cancer cells. Certain cyclic derivatives also exhibited strong inhibition of cell growth.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
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
Chemistry, Medicinal
Chuchu Li, Yuqiao Han, Zhengyang Wang, Yanan Yu, Chen Wang, Ziwei Ren, Yanzhi Guo, Tong Zhu, XuWen Li, Suzhen Dong, Mingliang Ma
Summary: Compound 42 showed excellent dual PI3K/mTOR inhibitory activity, significant in vitro and in vivo anti-tumoral activities, good kinase selectivity, low hepatotoxicity, modest plasma clearance and acceptable oral bioavailability. It is a promising PI3K/mTOR targeted anti-cancer drug candidate.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Chuan-jing Cheng, Kai-xin Liu, Man Zhang, Fu-kui Shen, Li-li Ye, Wen-bo Wu, Xiao-tao Hou, Er-wei Hao, Yuan-yuan Hou, Gang Bai
Summary: This study identified a novel natural inhibitor of HSP90, okicamelliaside (OCS), which selectively inhibits the formation of the HSP90-CDC37 protein complex and disrupts protein-protein interactions of HSP90-CDC37 to exert anti-tumor effects.
ACTA PHARMACOLOGICA SINICA
(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
Dongdong Zhang, Yixin Hu, Zhiqiang Hao, Yang Zhang, Shuhua Luo, Xin Dang, Ran Sun, Shixin Duan, Dan Lv, Faqin Jiang, Lei Fu
Summary: A novel batch of thiazole-containing mitochondrial targeting agents were designed and synthesized, with D1 exhibiting strong antiproliferative activity and significant mitochondrial inhibition on HeLa cancer cells.
BIOORGANIC CHEMISTRY
(2021)
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
Biochemistry & Molecular Biology
Nazarii Sabat, Abdelhakim Ouarti, Evelyne Migianu-Griffoni, Marc Lecouvey, Olivier Ferraris, Florian Gallier, Christophe Peyrefitte, Nadege Lubin-Germain, Jacques Uziel
Summary: Phosphoramidates obtained using the ProTide strategy have been known to enhance the biological activity of nucleosides. In this study, a series of prodrugs of SRO-91 were synthesized and investigated for their antitumor and antiviral activities. Two compounds showed inhibitory effects on cell proliferation, while another compound exhibited antiviral activity against Crimean-Congo Hemorrhagic Fever virus.
BIOORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Hui-Ping Xiao, Ya-Shuai Hao, Xin-Xiong Li, Peng Xu, Ming-Dong Huang, Shou-Tian Zheng
Summary: This study reports a giant Sb-rich polyoxometalate (POM) {Sb21Tb7W56}, which contains the largest number of Sb atoms in a POM. The Sb-rich POM exhibits broad-spectrum antitumor activity against various cancer cell lines and is capable of suppressing the growth and metastasis of a breast cancer in vivo.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Biochemistry & Molecular Biology
Kaiqing Ma, Mengchen Zhang, Xingkang Wu, Peng Yang, Caixia Yin
Summary: This study synthesized novel stemona alkaloid analogues, among which compound 3 was found to efficiently inhibit various colorectal cancer cells, including drug-resistant cells, by reducing the protein level of beta-catenin without affecting its mRNA level. The downstream proteins expression was also significantly inhibited, suggesting potential for compound 3 as a destabilizer of beta-catenin for the treatment of colorectal cancer patients.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Oncology
Jianchao Ge, Wandong Yu, Junhong Li, Hangbin Ma, Pengyu Wang, Yinghao Zhou, Yang Wang, Jun Zhang, Guowei Shi
Summary: The study identified USP16 as a novel deubiquitinase of c-Myc, showing that its downregulation significantly inhibited the growth of prostate cancer cells. USP16 regulates prostate cancer cell proliferation by deubiquitinating and stabilizing c-Myc, making it a potential therapeutic candidate for the treatment of prostate cancer.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2021)
Article
Biochemical Research Methods
Jianhua Cao, Xingkang Wu, Xuemei Qin, Zhenyu Li
Summary: Increasing cell passage number negatively affects HT29 cells, leading to decreased proliferation and migration ability, as well as distinct metabolomic differences among cells with different passage numbers, with arginine playing a key role in two key metabolic pathways, and exhibiting a synergistic effect with cisplatin.
JOURNAL OF PROTEOME RESEARCH
(2021)
Article
Plant Sciences
Shi-Fei Li, Xue Liang, Xing-Kang Wu, Xiang Gao, Li-Wei Zhang
Summary: Wikstroelide E is a potential HIV-latency-reversing agent that is 2500-fold more potent than prostratin. It reverses latent HIV infection by regulating multiple signaling pathways, with the Tat protein contributing to its robust activation of latent HIV. This study lays the foundation for the potential development of Wikstroelide E as an effective HIV-latency-reversing agent.
JOURNAL OF NATURAL PRODUCTS
(2021)
Article
Biochemistry & Molecular Biology
Li Gao, Wen-ge Zheng, Xing-kang Wu, Guan-hua Du, Xue-mei Qin
Summary: Baicalein, extracted from Scutellaria baicalensis, has shown protective effects against astrocyte senescence through regulation of leucine metabolism, suppression of SASP secretion, and inhibition of NF-kappa B and JAK2/STAT1 pathways. Experiment results in T98G cells and primary astrocytes of newborn SD rats support its potential in delaying senescence and enhancing cell viabilities.
ACS CHEMICAL NEUROSCIENCE
(2021)
Article
Plant Sciences
Xingkang Wu, Yufang Lu, Xuemei Qin
Summary: This study aimed to investigate the combined efficacy of Compound Kushen Injection (CKI)-derived combination strategies in p53-mutant CRC. The results showed that CKI combined with cisplatin (Cis) produced synergistic antitumor efficiency for p53-R273H/P309S mutant CRC cells. The combination of CKI and Cis reinforced cell death in a synergistic manner by inducing extrinsic apoptosis pathway.
JOURNAL OF ETHNOPHARMACOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Yongkang Yue, Tingting Zhao, Yuting Wang, Kaiqing Ma, Xingkang Wu, Fangjun Huo, Fangqin Cheng, Caixia Yin
Summary: The specific combination of human serum albumin and fluorescent dye improved the performance of in vivo fluorescence labeling. A covalent binding site in human serum albumin was found to bind a fluorescent dye with a specific turn-on fluorescence signal, which could be enhanced by drugs like ibuprofen, warfarin and clopidogrel. The fluorescence intensity amplification in a drug concentration dependent manner allowed real-time blood drug concentration monitoring in mice, with potential applications in tumor marking and surgical resection.
Article
Biochemistry & Molecular Biology
Xiao Li, Ruihong Hou, Xuemei Qin, Yanfei Wu, Xingkang Wu, Junsheng Tian, Xiaoxia Gao, Guanhua Du, Yuzhi Zhou
Summary: This study demonstrates for the first time the synergistic neuroprotective effects of SSA and AF, and reveals the involved mechanisms of metabolic disorders regulation and neuroinflammation inhibition.
MOLECULAR BIOLOGY REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Shi-Fei Li, Xiu-Yi Wang, Gong-Lu Li, Ying-Ying Jiao, Wen-Hao Wang, Xing-Kang Wu, Li-Wei Zhang
Summary: This study isolated several new diterpenes from the leaves of Wikstroemia chamaedaphne and found that some of them have potential to reverse HIV latency. Furthermore, these compounds exert their effects by activating STAT1 activity.
Article
Chemistry, Multidisciplinary
Xingkang Wu, Lu Wang, Zhenyu Li
Summary: The transcription factor p53 plays a crucial role in regulating cellular responses to environmental changes. In this study, a compound called PQ1 was identified as a potential inhibitor of p53 transcriptional activity, with potential therapeutic applications and research value.
Article
Chemistry, Multidisciplinary
Kaiqing Ma, He Yang, Xingkang Wu, Fangjun Huo, Fangqin Cheng, Caixia Yin
Summary: A new liposoluble cationic probe, KC8, was developed to detect NAD(P)H and monitor the abnormality of p53 in colorectal cancer cells in real time.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemistry & Molecular Biology
Shifei Li, Xiuyi Wang, Yuqin Yang, Xingkang Wu, Liwei Zhang
Summary: Four sesquiterpenes, five flavonoids, and two lignans were isolated from the roots of Wikstroemia chamaedaphne. Among them, oleodaphnone (2) exhibited effective activation of latent HIV, with time- and concentration-dependent effects. Transcriptome analysis revealed that oleodaphnone regulated multiple signaling pathways, providing a potential basis for its development as an HIV latency-reversing agent.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Xingkang Wu, Yushuang Ma, Lu Wang, Xuemei Qin
Summary: This article reviews the common pathological mechanisms between psoriasis and cancer, including the interaction between cell proliferation and an abnormal immune microenvironment, metabolic reprogramming, and epigenetic reprogramming. The article also discusses the shared therapeutic agents and drug targets between psoriasis and cancer. The author suggests that investigating psoriasis from a cancer perspective can enrich research strategies related to psoriasis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Urology & Nephrology
Yangyun Wang, Chaoliang Shi, Yang Wang, Wei Jiao, Xilong Wang, Jun Zhang, Guowei Shi, Denglong Wu
Summary: The study found a close association between severe overactive bladder (OAB) and female sexual dysfunction and sexual satisfaction of partners. Urgency score was significantly correlated with female sexual dysfunction, and urge incontinence was found to be the most significant factor affecting the sexual satisfaction of partners.
UROLOGIA INTERNATIONALIS
(2021)
Article
Biochemistry & Molecular Biology
Ali Mehri, Karim Mahnam, Hajar Sirous, Mahmoud Aghaei, Leila Rafiei, Mahboubeh Rostami
Summary: One potential approach for tumor therapy is inhibiting the binding between MDM2 and p53 to reactivate p53 in tumor cells. In this study, Monastrol derivatives were designed as MDM2 inhibitors and evaluated for their cytotoxicity on cancer cells. Compound 5d showed the best inhibitory results in silico and in vitro experiments. These findings suggest that Monastrol derivatives have the potential to be candidates for MDM2 inhibition.
CHEMICAL BIOLOGY & DRUG DESIGN
(2024)
