Article
Chemistry, Medicinal
Hualong Mo, Ruiqiang Zhang, Yajun Chen, ShuTing Li, Yao Wang, Wenbo Zou, Qiman Lin, Deng-Gao Zhao, Yarong Du, Kun Zhang, Yan-Yan Ma
Summary: Compound 21 is an effective anticancer agent that inhibits tumor growth by inhibiting autophagy and inducing cell apoptosis.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Simin Sun, Wenwen Zhao, Yongliang Li, Ziwei Chi, Xixi Fang, Qiang Wang, Zhiwu Han, Yepeng Luan
Summary: The study focused on the design and synthesis of a series of HDAC inhibitors, identifying compound 6h as a promising candidate with potent antitumor effects. Compound 6h exhibited high cytotoxicity against various cancer cell lines, arrested cell cycle, induced apoptosis, and demonstrated anti-migration and anti-angiogenesis activities. Additionally, compound 6h increased the expression of acetylated alpha-tubulin and acetylated histone H3, fitting well into the active sites of HDAC2 and 6, suggesting its potential for further preclinical studies.
BIOORGANIC CHEMISTRY
(2021)
Article
Oncology
Roisin M. Connolly, Fengmin Zhao, Kathy D. Miller, Min-Jung Lee, Richard L. Piekarz, Karen L. Smith, Ursa A. Brown-Glaberman, Jennifer S. Winn, Bryan A. Faller, Adedayo A. Onitilo, Mark E. Burkard, George T. Budd, Ellis G. Levine, Melanie E. Royce, Peter A. Kaufman, Alexandra Thomas, Jane B. Trepel, Antonio C. Wolff, Joseph A. Sparano
Summary: The combination of entinostat and exemestane did not improve survival in patients with AI-resistant advanced HR-positive, HER2-negative breast cancer. E2112 phase III trial: no benefit seen in adding HDAC inhibitor entinostat to exemestane in advanced breast cancer.
JOURNAL OF CLINICAL ONCOLOGY
(2021)
Review
Oncology
Amandine Badie, Christian Gaiddon, Georg Mellitzer
Summary: Our understanding of the identity of many cancers has greatly increased in recent years, leading to progress in early detection and treatment options. However, gastric cancer remains poorly treated with low survival rates. The lack of possibilities for early detection and the variations between tumors of gastric cancer patients are major challenges. Histone Deacetylases (HDACs) have been identified to be potentially related to gastric cancer. In this review, we summarize the current knowledge on the role of HDACs in gastric cancer development and their potential as early detection markers and targets for new treatment options.
Review
Pharmacology & Pharmacy
Hae Jin Kee, Inkyeom Kim, Myung Ho Jeong
Summary: This article provides an overview of the pathogenesis of hypertension, current anti-hypertensive drugs, and the need for novel drugs. It focuses on the role and regulatory mechanisms of HDACs in hypertension and discusses the progress in developing HDAC inhibitors as potential therapeutic targets.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Chemistry, Inorganic & Nuclear
Elisabetta Gabano, Beatrice Rangone, Elena Perin, Giulia Caron, Giuseppe Ermondi, Maura Vallaro, Valentina Gandin, Cristina Marzano, Alessandra Barbanente, Nicola Margiotta, Mauro Ravera
Summary: The study investigated Pt(iv) complexes based on (SP-4-2)-dichlorido(cyclohexane-1,4-diamine)platinum(ii) (kiteplatin) and the histone deacetylase inhibitor 2-(2-propynyl)octanoic acid (POA), comparing their antiproliferative activity on cancer cell lines and studying their cell penetration properties and inhibition of tumor growth in mice.
DALTON TRANSACTIONS
(2021)
Review
Oncology
Fengyi Guo, Hongjing Wang
Summary: This review summarizes the classification and mechanisms of action of histone deacetylase and the clinical application of their inhibitors in ovarian cancer. Histone deacetylase inhibitors show promising potential as anti-cancer drugs, and combination therapy with other anticancer drugs for synergistic effects can improve efficacy.
FRONTIERS IN ONCOLOGY
(2022)
Review
Cell Biology
Bingyi Zhou, Deliang Liu, Yuyong Tan
Summary: Cancer is the second leading cause of death worldwide, with digestive system cancers being a primary contributor. Acetylation and deacetylation play crucial roles in cancer development, with HDAC6 being a widely studied enzyme that is upregulated in various tumors and associated with clinicopathological characteristics. There is ongoing research on HDAC6 inhibitors and their potential in inhibiting tumor growth.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Oncology
Anna Wawruszak, Marta Halasa, Estera Okon, Wirginia Kukula-Koch, Andrzej Stepulak
Summary: Breast cancer is the most common malignancy affecting women worldwide, with valproic acid showing promising potential in inhibiting cancer cell proliferation. Studies have demonstrated that VPA, a member of the group of histone deacetylase inhibitors, can modulate multiple signaling pathways and improve the effectiveness of current treatment methods for breast cancer.
Review
Oncology
Jason Lin, Shang-Chuen Wu
Summary: This review examines the role of protein serotonylation in transcriptional regulation, its potential impact on the epigenetic landscape, and its implications in lung and other types of cancer. The review discusses the mechanistic details of serotonylation and its connections to the epigenome, as well as the role of transglutaminase 2, in order to guide the development of optimized histone deacetylase inhibitor designs or combination therapies for cancer treatment.
Article
Oncology
Hui Lyu, Defu Hou, Hao Liu, Sanbao Ruan, Congcong Tan, Jiande Wu, Chindo Hicks, Bolin Liu
Summary: This study aims to determine the mechanisms of action of the histone deacetylase inhibitor panobinostat in TNBC and provide a rationale for effective drug combinations against this aggressive disease.
NPJ PRECISION ONCOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Svetlana Demyanenko, Valentina Dzreyan, Svetlana Sharifulina
Summary: Cerebral ischemia is the second leading cause of death worldwide, requiring multimodal stroke therapy. Histone deacetylase inhibitors have shown to be effective in protecting the brain from ischemic damage by inducing neurogenesis and angiogenesis in damaged brain areas, promoting functional recovery after stroke.
Review
Oncology
Anna Wawruszak, Lidia Borkiewicz, Estera Okon, Wirginia Kukula-Koch, Syeda Afshan, Marta Halasa
Summary: Breast cancer remains a challenging malignancy with varying responses to therapy, requiring the development of new active agents to improve the current treatment regimens. Vorinostat (SAHA) shows promise in the therapy of different histological subtypes of breast cancer, either alone or in combination with other anticancer agents, based on preclinical and clinical trials data.
Review
Pharmacology & Pharmacy
Jianglei Li, Meihong Yu, Shifeng Fu, Deliang Liu, Yuyong Tan
Summary: This review summarizes the research progress and underlying mechanism of ACY-1215 in cancer and other human diseases.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Oncology
Sofia Isolde Baer, Alexandra Dittmer, Bianca Nitzsche, Gohar Ter-Avetisyan, Michael Faehling, Adrian Klefenz, Leonard Kaps, Bernhard Biersack, Rainer Schobert, Michael Hoepfner
Summary: The potential suitability of the novel chimeric inhibitor Broxbam for the treatment of liver cancer was investigated. The study demonstrated that Broxbam inhibited cell proliferation and induced apoptosis in liver cancer cell lines. It exerted its effects through inhibition of HDAC6 and tubulin polymerization, and exhibited anti-angiogenic activity. The findings suggest that Broxbam is a promising candidate for liver cancer treatment.
INTERNATIONAL JOURNAL OF ONCOLOGY
(2022)
Editorial Material
Oncology
Dazhao Mi, Yuzhan Li, Yihua Chen
Summary: This article provides an overview of the role of SHP2 protein tyrosine phosphatase in cancer-related signaling pathways, as well as the therapeutic strategies targeting SHP2, including PTP inhibitors, allosteric inhibitors, and SHP2-targeting PROTACs. The benefits and limitations of these strategies are discussed. The opportunities and challenges of targeting SHP2 are also presented.
ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY
(2023)
Article
Oncology
Yuzhu Zhang, Jing Chen, Dazhao Mi, Jun Ling, Huachao Li, Peng He, Ning Liu, Qianjun Chen, Yihua Chen, Luqi Huang
Summary: In this study, the natural product harmine was identified as a potential compound for treating triple-negative breast cancer (TNBC). The compound was further modified and optimized to obtain a lead compound, YH677, which showed strong anti-proliferative and anti-migratory effects in vitro and suppressed breast cancer growth and metastasis in vivo. Mechanistic studies revealed that YH677 inhibits the expansion of cancer stem cells by regulating the TGF beta/Smad signaling pathway.
Correction
Oncology
Yuzhu Zhang, Jing Chen, Dazhao Mi, Jun Ling, Huachao Li, Peng He, Ning Liu, Qianjun Chen, Yihua Chen, Luqi Huang
Article
Biochemistry & Molecular Biology
Yujing Wang, Shuping Wang, Qingqing Wang, Wanyu Tang, Li Lin, Tao Zhang, Meichun Hu, Xiaobo Wang
Summary: Triple-negative breast cancer (TNBC) is a highly malignant breast tumor with poor prognosis and high recurrence rate. The development of new strategies and effective agents is urgently needed to overcome resistance and improve therapeutic effectiveness. A novel luminescent monofunctional platinum (II) complex, I2BC-Pt, based on BODIPY derivative, showed excellent photodynamic therapy (PDT) effect against TNBC cells, inducing apoptosis and inhibiting DNA repair. It has the potential to be developed as a BODIPY-based photosensitizer for TNBC therapy.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2023)
Article
Chemistry, Medicinal
Peng He, Juanjuan Feng, Xinting Xia, Yue Sun, Jia He, Tian Guan, Yangrui Peng, Xueli Zhang, Mingyao Liu, Xiufeng Pang, Yihua Chen
Summary: HP661 is a highly effective OXPHOS inhibitor that can inhibit mitochondrial oxygen consumption in high OXPHOS lung cancer cells. It also shows significant sensitivity in MEK inhibitor-resistant lung cancer cells and has therapeutic efficacy against high OXPHOS lung cancer.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Jia He, Luzhen Wang, DaZhao Mi, Tian Guan, Wenjing Liu, Peng He, Haijun Gu, Yuzhan Li, Yangrui Peng, Ai-Qun Jia, Ceshi Chen, Yihua Chen
Summary: JH530 is a drug that can induce cell death in triple-negative breast cancer cells and has shown significant suppression of tumor growth in vitro and in vivo.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Chenyu Zhu, Shuyin Ze, Ronghui Zhou, Xinyu Yang, Haojie Wang, Xiaolei Chai, Meimiao Fang, Mingyao Liu, Yonghui Wang, Weiqiang Lu, Qiong Xie
Summary: Recent studies and clinical evidence have shown that adenosine A2A receptor (A2AR) antagonists have great potential as novel approaches for cancer immunotherapy. Through the screening of a compound library, a pyridinone hit compound with weak A2AR antagonistic activity was identified, and further studies led to the discovery of a series of pyridinone derivatives with strong potency. Compound 38 demonstrated potent A2AR antagonistic activity, good metabolic stability, and excellent oral bioavailability, and also effectively enhanced the activation and killing ability of T cells. In addition, it exhibited excellent in vivo antitumor activity, making it a promising candidate for cancer immunotherapy.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Medicine, Research & Experimental
Yali Wang, Wenbo Zhou, Jianfeng Chen, Jinghong Chen, Peng Deng, Huang Chen, Yichen Sun, Zhaoliang Yu, Diwen Pang, Lizhen Liu, Peili Wang, Jing Han Hong, Bin Tean Teh, Huiqiang Huang, Wenyu Li, Zhengfang Yi, Soon Thye Lim, Yihua Chen, Choon Kiat Ong, Mingyao Liu, Jing Tan
Summary: A new and potent STAT3 inhibitor, WB737, has been developed as a potential therapeutic option for NKTL. It selectively inhibits NKTL with STAT3-activating mutations and suppresses both canonical and noncanonical STAT3 signaling. WB737 shows significant antitumor effects with minimal toxicity, providing a promising strategy for treating NKTL patients.
Article
Medicine, Research & Experimental
Lin Zhang, Min Wu, Weikai Guo, Shuangshuang Zhu, Shen Li, Shiyi Lv, Yan Li, Layang Liu, Yajing Xing, Huang Chen, Mingyao Liu, Shihong Peng, Yihua Chen, Zhengfang Yi
Summary: BCL6 is a transcriptional repressor that plays a role in immune cell differentiation, DNA damage repair, cell cycle, and apoptosis. A small molecule compound called WK499 has been identified as a inhibitor of BCL6, which inhibits the proliferation of AML cells and enhances the sensitivity of AML to chemotherapy. WK499 achieves this by disrupting the interactions between BCL6 and its corepressor proteins, leading to changes in downstream genes and induction of cell cycle arrest and apoptosis.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Review
Chemistry, Medicinal
Dazhao Mi, Yuzhan Li, Haijun Gu, Yan Li, Yihua Chen
Summary: Proteolysis-targeting chimeras (PROTACs) have gained significant attention as an emerging modality in drug discovery. After over 20 years of development, accumulated studies have shown that PROTACs offer unique advantages over traditional therapy in terms of target scope, efficacy, and overcoming drug resistance. However, the limited availability of E3 ligases, essential components of PROTACs, poses a challenge for their design. This review provides a systematic summary of the current status of E3 ligases and corresponding ligands for PROTACs design, including their discovery history, design principles, application benefits, and potential limitations. The prospects and future directions in this field are also briefly discussed.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Engineering, Chemical
Wenbin Qian, Meichun Hu, Yanting Su, Shigang Shan, Zhenwang Zhang, Lei Hu, Xiaoqing Lin
Summary: In this study, the adsorption rate of geniposidic acid (GSA) on a fixed-bed column packed with porous adsorbents was thoroughly investigated using a Fick pore diffusion model based on numerical simulation and 3D visualization. The experimental breakthrough curves of GSA were studied under different operating conditions, and a maximum adsorption capacity of 637.5 mmol L-1 at 298.5 K was achieved. The modeling method for the adsorption packed column involved coupling mass transfer equations with a steady velocity field obtained from Navier-Stokes equation, and a finite element method was used for solving the equation system. By analyzing the influences of operation conditions on mass fluxes induced by convection and diffusion, the existence of forming and transferring periods of the mass transfer zone (MTZ) was confirmed.
SEPARATION AND PURIFICATION TECHNOLOGY
(2023)
Article
Chemistry, Medicinal
Chenyu Zhu, Shuyin Ze, Ronghui Zhou, Xinyu Yang, Haojie Wang, Xiaolei Chai, Meimiao Fang, Mingyao Liu, Yonghui Wang, Weiqiang Lu, Qiong Xie
Summary: Recent studies and clinical evidence have shown that adenosine A2A receptor (A2AR) antagonists have great potential in cancer immunotherapy. Through screening, compound 38, a pyridinone derivative, was identified as a potent A2AR antagonist with good stability and high bioavailability. Furthermore, compound 38 effectively enhanced the activation of T cells in vitro and demonstrated excellent antitumor activity in vivo, making it a promising candidate for cancer immunotherapy.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Inorganic & Nuclear
Li Xun-Yi, Wang Yu-Jing, Zhou Zi-Mo, Fang Xiao, Wang Qing-Qing, Hu Mei-Chun, Yang Xiao-Song, Wang Xiao-Bo
Summary: A binuclear monofunctional platinum(II) complex, [Pt-2(BPA-TPA)Cl-2]Cl-2, containing 2,6-bis((bis(pyridin-2-ylmethyl)amino)methyl)pyridine was synthesized and characterized. The DNA-cleaving activity of Pt-2-BPA-TPA at a low concentration was demonstrated using agarose gel electrophoresis experiments. In cytotoxicity studies, Pt-2-BPA-TPA showed enhanced anticancer activity compared with cisplatin, and mechanistic studies suggested that Pt-2-BPA-TPA induces apoptosis by triggering DNA damage and upregulating downstream cellular signaling cascades.
CHINESE JOURNAL OF INORGANIC CHEMISTRY
(2023)
Review
Chemistry, Medicinal
Weikai Guo, Manjie Wang, Zhengfan Yang, Danyang Liu, Borui Ma, Yanqun Zhao, Yihua Chen, Yanzhong Hu
Summary: This article comprehensively reviews the structure, physiological functions, and recent progress of GRP78, and discusses the merits and demerits of GRP78 inhibitors as well as novel strategies for drug discovery targeting GRP78. The feasibility of PROTACs and covalent inhibition as new opportunities for targeted antitumor therapy are also explored.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)