Article
Chemistry, Medicinal
Rachel J. Harding, Ivan Franzoni, Mandeep K. Mann, Magdalena M. Szewczyk, Bijan Mirabi, Renato Ferreira de Freitas, Dominic D. G. Owens, Suzanne Ackloo, Alexej Scheremetjew, Kevin A. Juarez-Ornelas, Randy Sanichar, Rachel J. Baker, Christian Dank, Peter J. Brown, Dalia Barsyte-Lovejoy, Vijayaratnam Santhakumar, Matthieu Schapira, Mark Lautens, Cheryl H. Arrowsmith
Summary: Inhibition of HDAC6-UBD is a promising strategy for treating cancers, and a potent chemical probe SGC-UBD253 (25) has been developed for targeting HDAC6-UBD. A methylated derivative SGC-UBD253N (32) was also identified as a negative control. These findings provide insights into the biological function of HDAC6-UBD and the therapeutic potential of targeting this domain.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Oncology
Scott W. Strum, Laszlo Gyenis, David W. Litchfield
Summary: CSNK2 is frequently dysregulated in cancer, influencing apoptosis evasion, proliferation, cell invasion/metastasis, and cell cycle control. It holds prognostic significance in various cancers, and inhibition in xenograft experiments shows positive treatment response.
BRITISH JOURNAL OF CANCER
(2022)
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)
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
Immunology
Martina Mazzocchi, Susan R. Goulding, Noelia Morales-Prieto, Tara Foley, Louise M. Collins, Aideen M. Sullivan, Gerard W. O'Keeffe
Summary: The peripheral administration of Class IIa-specific HDIs may have neuroprotective effects in Parkinson's disease.
BRAIN BEHAVIOR AND IMMUNITY
(2022)
Article
Biochemistry & Molecular Biology
Jakub Ptacek, Ivan Snajdr, Jiri Schimer, Zsofia Kutil, Jana Mikesova, Petra Baranova, Barbora Havlinova, Werner Tueckmantel, Pavel Majer, Alan Kozikowski, Cyril Barinka
Summary: This article compares hydroxamate-based HDAC6-selective inhibitors commonly used in the treatment of neurological and psychiatric disorders with a novel HDAC6 inhibitor containing the difluoromethyl-1,3,4-oxadiazole function (compound 7). In vitro screening revealed HDAC10 as a primary off-target for hydroxamate-based HDAC6 inhibitors, while compound 7 showed exquisite selectivity over all other HDAC isoforms. Cell-based assays showed lower potency for all compounds when using tubulin acetylation as a surrogate readout. Additionally, the limited selectivity of some HDAC6 inhibitors was shown to be linked to cytotoxicity in RPMI-8226 cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Chemistry, Medicinal
Xin-Hui Zhang, Qin-Ma, Hui-Pan Wu, Mussa Yussuf Khamis, Yi-Han Li, Li-Ying Ma, Hong-Min Liu
Summary: In this translation, the essential role of HDACs in maintaining homeostasis is discussed, with a focus on the unique characteristics and diverse functions of HDAC6. HDAC6 inhibitors have shown promising potential in treating various diseases with reduced toxicity. Progress has been made in defining the crystal structures of HDAC6 catalytic domains, which can inform the development of HDAC6 inhibitors.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Tianyi Zhang, Xiaoyan Zhao, Xiangpei Sun, Wei Tian, Chongqing Wang, Mingping Wang, Yi Zhang, Xin Chen, Canhui Zheng
Summary: This study aimed to discover novel HDAC6 selective inhibitors, and a new class of compounds with excellent inhibitory activities and selectivity was obtained through structural optimization of the previously reported inhibitor 7g. These compounds showed inhibitory effects on HDAC6, a protein associated with diseases such as cancer, and may have lower toxicity to normal cells and tissues.
JOURNAL OF SAUDI CHEMICAL SOCIETY
(2022)
Article
Biochemistry & Molecular Biology
Rafael Flores, Shoaib Iqbal, Donald Sikazwe
Summary: In this study, we synthesized and partially evaluated 20 amides as potential drugs for treating Alzheimer's disease. Compound 8 showed promising characteristics, including affinity for sigma-1, inhibition of HDAC-6, and antioxidant activity, making it suitable for further research and optimization.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Longlong Wang, Etori Aguiar Moreira, Georg Kempf, Yasuyuki Miyake, Blandina I. Oliveira Esteves, Amal Fahmi, Jonas Schaefer, Birgit Dreier, Yohei Yamauchi, Marco P. Alves, Andreas Plueckthun, Patrick Matthias
Summary: The deacetylase HDAC6 has tandem catalytic domains and a zinc finger domain binding ubiquitin, which promotes the formation of aggresomes and stress granules. Influenza A virus subverts this pathway to facilitate infection. Designed ankyrin repeat proteins (DARPins) targeting the ZnF can impair viral infection and reduce the formation of SGs and aggresomes.
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
Genetics & Heredity
Jingjing Pu, Amit Sharma, Jian Hou, Ingo G. H. Schmidt-Wolf
Summary: With increasing knowledge about histone modifications and its role in disease conditions like cancer and neurodegeneration, histone deacetylase 6 (HDAC6) is considered to be at the forefront of research advancing clinical translation in these areas.
Article
Chemistry, Physical
Yogesh Mahadu Khetmalis, Bakhya Shree, Boddupalli Venkata Siva Kumar, Markus Schweipert, Cecile Debarnot, Fathima Ashna, Murugesan Sankaranarayanan, Jamma Trinath, Vivek Sharma, Franz -Josef Meyer-Almes, Kondapalli Venkata Gowri Chandra Sekhar
Summary: A series of novel tetrahydroisoquinoline (THIQ) compounds were synthesized and evaluated as selective inhibitors of histone deacetylase 6 (HDAC 6). The compounds demonstrated potent antiproliferative activities and inhibited the colony formation in cancer cells. B10 and B24 showed the highest selectivity towards HDAC 6 with IC50 values of 0.3 μM and 0.4 μM respectively. The inhibition of cancer cell proliferation by B21 and B24 was attributed to cell cycle arrest in G1 phase and apoptotic death of the cancer cells.
JOURNAL OF MOLECULAR STRUCTURE
(2023)
Article
Chemistry, Medicinal
Yuqi Jiang, Jie Xu, Kairui Yue, Chao Huang, Mengting Qin, Dongyu Chi, Qixin Yu, Yue Zhu, Xiaohan Hou, Tongqiang Xu, Min Li, C. James Chou, Xiaoyang Li
Summary: The study focused on modifying HDAC inhibitors to deactivate the Michael reaction in order to improve their potency. Compound 11h showed significant improvements in both HDAC inhibitory activity and cell-based antitumor assay, demonstrating potential for clinical application and efficacy against AML.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Agricultural Engineering
Xuefeng Lu, Tae Kyung Hyun
Summary: Post-translational histone modifications, such as histone acetylation, play key roles in regulating gene expression in plant growth, development, and stress responses. The research found that HDAC inhibitors led to hyperacetylation of histone H3, enhancing MeJA-induced ginsenoside production in ginseng adventitious roots. Additionally, the study identified specific PgHDACs that may serve as crucial factors in controlling MeJA-induced ginsenoside production.
INDUSTRIAL CROPS AND PRODUCTS
(2021)