Review
Pharmacology & Pharmacy
Milan Beljkas, Aleksandra Ilic, Alen Cebzan, Branko Radovic, Nemanja Djokovic, Dusan Ruzic, Katarina Nikolic, Slavica Oljacic
Summary: HDAC6 is a key regulator of the balance of acetylation of non-histone proteins, and its overexpression is associated with various malignancies. Dual-target HDAC6 inhibitors have become a new trend in cancer treatment due to the low efficacy and off-target effects of current inhibitors.
Article
Oncology
Bernhard Biersack, Sibel Polat, Michael Hoepfner
Summary: Histone deacetylases (HDACs) are epigenetic regulators that affect chromatin condensation and cancer proliferation. HDAC inhibitors are promising drugs for cancer treatment. However, there are limitations and resistance issues in clinical application, leading to the search for new HDAC inhibitors. Kinase inhibitors, when used in combination with HDAC inhibitors, show synergistic anticancer effects.
SEMINARS IN CANCER BIOLOGY
(2022)
Review
Medicine, Research & Experimental
Janice Jacson Mandumpala, Stephin Baby, Antriya Annie Tom, Chandraiah Godugu, Nagula Shankaraiah
Summary: Triple-negative breast cancer (TNBC) is a highly lethal subtype of breast cancer with limited treatment options due to its complexity, drug resistance, and lack of therapeutic targets. Recent studies have shown the importance of epigenetic regulation in TNBC development, with a focus on histone methyltransferases and histone demethylases as potential targets for new targeted therapies in TNBC treatment.
Review
Oncology
Rihan Hai, Liuer He, Guang Shu, Gang Yin
Summary: Epigenetic dysregulation, specifically through histone post-translational modifications, plays a crucial role in tumour pathogenesis. Histone deacetylases and histone acetyltransferases are pivotal epigenetic modulators that regulate the transcription of oncogenes and tumour suppressor genes, influencing a host of pathological processes in cancer development.
FRONTIERS IN ONCOLOGY
(2021)
Article
Chemistry, Medicinal
Mengjiao Zhou, Minjian Yuan, Meng Zhang, Chenyi Lei, Omer Aras, Xiaohong Zhang, Feifei An
Summary: Histone deacetylase inhibitors (HDACis) are considered key targets in cancer therapy, but their efficacy as a single therapeutic agent is limited, leading to drug resistance. Combination therapies involving HDACis with other antitumor therapies are being studied to enhance therapeutic efficacy and reduce drug resistance, with a focus on chemotherapy, radiotherapy, phototherapy, targeted therapy, and immunotherapy.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Long Xu, Xiaoyu Yan, Jian Wang, Yuanxin Zhao, Qingqing Liu, Jiaying Fu, Xinyi Shi, Jing Su
Summary: This article provides an overview of ovarian cancer metastasis and the dysregulated expression of HDACs in ovarian cancer. It discusses the roles of HDACs in the regulation of ovarian cancer metastasis and highlights the importance of developing compounds that target HDACs in the future of ovarian cancer therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Monika Pieniawska, Katarzyna Izykowska
Summary: Histone deacetylases (HDACs) are enzymes that alter chromatin structure, affecting gene expression. They play important roles in T-cell development and function. This review summarizes the current understanding of the role of HDACs in early T-cell development and mature lymphocyte function.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Linda Schaeker-Huebner, Reza Haschemi, Thomas Buech, Fabian B. Kraft, Birke Brumme, Andrea Schoeler, Robert Jenke, Jens Meiler, Achim Aigner, Gerd Bendas, Finn K. Hansen
Summary: In this study, we investigated the structure-activity and structure-physicochemical property relationships of a series of compounds targeting HDAC1 and HDAC2. We identified a potent and selective inhibitor, LSH-A54, which showed favorable physicochemical properties and exhibited inhibitory effects on breast cancer cells by tightly binding to HDAC1.
Review
Biochemistry & Molecular Biology
Xue-Song Xiang, Peng-Cheng Li, Wen-Quan Wang, Liang Liu
Summary: Pancreatic cancer is the seventh leading cause of cancer death worldwide and novel treatment options for PDAC are urgently needed. The dysregulation of HDACs has been identified in association with PDAC and may represent a therapeutic breakthrough. However, the contributions of HDACs to PDAC remain controversial and pharmacokinetic challenges limit the application of HDACis in PDAC.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2022)
Article
Oncology
Marina Baretti, Adrian. G. G. Murphy, Marianna Zahurak, Nicole Gianino, Rose Parkinson, Rosalind Walker, Tamara. Y. Y. Lopez-Vidal, Lei Zheng, Gary Rosner, Nita Ahuja, Schalper Kurt, Nilofer. S. S. Azad
Summary: This study evaluated the efficacy of PD-1 immune checkpoint inhibitor therapy in combination with DNMT and HDAC inhibitors in MMRp CRC. The results showed limited effectiveness of this combination therapy with relatively high side effects. Further research is needed to understand the epigenetic-induced immune changes and expand the potential applicability of checkpoint inhibitors in this setting.
CLINICAL EPIGENETICS
(2023)
Article
Chemistry, Medicinal
Xingrui He, Zi Hui, Li Xu, Renren Bai, Yuan Gao, Zongcheng Wang, Tian Xie, Xiang-Yang Ye
Summary: Histone deacetylases (HDACs) are important enzymes involved in the removal of acetyl groups from lysine residues, and have shown potential therapeutic applications in cancer and various diseases. There are currently numerous HDAC inhibitors under clinical investigation, aiming to provide up-to-date information for drug discovery programs.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Neurosciences
Bryan McClarty, Guadalupe Rodriguez, Hongxin Dong
Summary: The study showed that the HDAC inhibitor CI-994 at different doses could reduce motor and memory side effects induced by haloperidol in aged mice. A dose of 20 mg/kg was effective in improving motor coordination and mitigating memory impairment in aged mice. Biochemical analyses indicated an increase in histone acetylation and expression of the dopamine 2 receptor gene in aged mice after administration of CI-994 at 20 mg/kg.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Oncology
Steven Behnisch-Cornwell, Christoph W. Grathwol, Lukas Schulig, Anika Voigt, Daniel Baecker, Andreas Link, Patrick J. Bednarski
Summary: The protein expression profiles of HDAC/Sirtuin isoenzymes and the potencies of anticancer drugs were compared in different cancer cell lines, and correlations were found between enzyme expression and anticancer activity. However, the correlations between protein expression and mRNA expression were not the same. Combination treatments with HDAC inhibitors and anticancer drugs showed synergistic effects. Additionally, HDAC inhibitors enhanced the cytotoxicity of certain anticancer drugs.
Article
Genetics & Heredity
Jingjing Pu, Ting Liu, Amit Sharma, Ingo G. H. Schmidt-Wolf
Summary: This study investigates the interactions between HDAC6-induced lncRNA (LINC00152) and its potential sponge miRNA (hsa-miR-499a-5p) in multiple myeloma.
BMC MEDICAL GENOMICS
(2023)
Article
Chemistry, Multidisciplinary
Kotoko Sakamoto, Ayumi Hirano, Rika Hidaka, Akinobu Z. Suzuki, Taro Ueno, Toshiaki Furuta
Summary: This study reports a genetically targeted HDAC inhibitor CM-Bhc-SAHA, which can optochemically inhibit endogenous HDAC activity in mammalian cells expressing porcine liver esterase treated with CM-Bhc-SAHA and irradiated with 405 nm light.
CHEMICAL COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Glaucio Monteiro Ferreira, Juliana Gallottini de Magalhaes, Vinicius Goncalves Maltarollo, Thales Kronenberger, Arasu Ganesan, Flavio da Silva Emery, Gustavo Henrique Goulart Trossini
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2020)
Article
Biochemistry & Molecular Biology
Liyun Liang, Haiwen Wang, Yongliang Du, Bingling Luo, Ning Meng, Meifeng Cen, Peng Huang, A. Ganesan, Shijun Wen
BIOORGANIC CHEMISTRY
(2020)
Review
Biochemistry & Molecular Biology
Angel R. de Lera, A. Ganesan
CURRENT OPINION IN CHEMICAL BIOLOGY
(2020)
Editorial Material
Biochemistry & Molecular Biology
Akane Kawamura, A. Ganesan
CURRENT OPINION IN CHEMICAL BIOLOGY
(2020)
Article
Chemistry, Medicinal
Terence C. S. Ho, Alex H. Y. Chan, A. Ganesan
JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Article
Infectious Diseases
Vitor Coutinho Carneiro, Isabel Caetano de Abreu Silva, Murilo Sena Amaral, Adriana S. A. Pereira, Gilbert Oliveira Silveira, David da Silva Pires, Sergio Verjovski-Almeida, Frank J. Dekker, Dante Rotili, Antonello Mai, Eduardo Jose Lopes-Torres, Dina Robaa, Wolfgang Sippl, Raymond J. Pierce, M. Teresa Borrello, A. Ganesan, Julien Lancelot, Silvana Thiengo, Monica Ammon Fernandez, Amanda Roberta Revoredo Vicentino, Marina Moraes Mourao, Fernanda Sales Coelho, Marcelo Rosado Fantappie
PLOS NEGLECTED TROPICAL DISEASES
(2020)
Article
Chemistry, Medicinal
Maria Teresa Borrello, Hanae Benelkebir, Adam Lee, Chak Hin Tam, Manar Shafat, Stuart A. Rushworth, Kristian M. Bowles, Leon Douglas, Patrick J. Duriez, Sarah Bailey, Simon J. Crabb, Graham Packham, A. Ganesan
Summary: Novel tranylcypromine analogues with a carboxamide at the 4-position of the aryl ring showed potent inhibition of LSD1 and cell proliferation in AML cell lines. The carbamate derivatives of tranylcypromines were inactive in LSD1 inhibition but showed similar potency in cell-based assays, suggesting they can act as metabolically labile prodrugs with superior pharmacokinetics.
Article
Chemistry, Medicinal
Miguel M. Vaidergorn, Flavio da Silva Emery, A. Ganesan
Summary: Over the past 15 years, significant progress has been made in the application of fragment-based drug discovery (FBDD) to epigenetic drug discovery (EPIDD), especially in prospecting for bromodomain binding ligands.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Muhammad Nadeem-ul-Haque, Anila Bashir, Humira Karim, Sadiq Noor Khan, Zafar Ali Shah, Almas Jabeen, Shaista Qayyum, A. Ganesan, M. Iqbal Choudhary, Farzana Shaheen
Summary: This study investigated the synthesis of [1-8-N alpha C]-zanriorb A1 from the medicinal plant Zanthoxylum riedelianum. The solution-phase route produced a mixture of proline rotamers, while the on-resin cyclization was less successful. Analogues of zanriorb A1 were also synthesized, and one compound showed strong anti-inflammatory potential.
JOURNAL OF PEPTIDE SCIENCE
(2022)
Article
Chemistry, Multidisciplinary
Mohammed Aldholmi, Rizwan Ahmad, Daniel Carretero-Molina, Ignacio Perez-Victoria, Jesus Martin, Fernando Reyes, Olga Genilloud, Lea Gourbeyre, Thierry Gefflaut, Hanne Carlsson, Alexei Maklakov, Ellis O'Neill, Robert A. Field, Barrie Wilkinson, Maria O'Connell, A. Ganesan
Summary: The study discovered that euglenatides from Euglena gracilis can inhibit pathogenic fungi and cancer cells, and bear resemblance to nemamides in Caenorhabditis elegans. Molecular network analysis also revealed the presence of multiple euglenatide-like metabolites in Euglena species.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Oncology
Ipek Bulut, Adam Lee, Buse Cevatemre, Dusan Ruzic, Roman Belle, Akane Kawamura, Sheraz Gul, Katarina Nikolic, A. Ganesan, Ceyda Acilan
Summary: The newly developed LSD1/HDAC6 dual inhibitor iDual can inhibit the growth of leukemia cells by simultaneously targeting HDAC6 and LSD1, and it can enhance drug-induced apoptosis when used in combination with doxorubicin.
Article
Pharmacology & Pharmacy
Dusan Ruzic, Bernhard Ellinger, Nemanja Djokovic, Juan F. Santibanez, Sheraz Gul, Milan Beljkas, Ana Djuric, Arasu Ganesan, Aleksandar Pavic, Tatjana Srdic-Rajic, Milos Petkovic, Katarina Nikolic
Summary: This report describes the design and discovery of two selective HDAC6 inhibitors and two non-selective HDAC inhibitors. Molecular modeling found that the linker chemistry of the inhibitors influences their potency. A novel non-selective HDAC inhibitor with a longer linker showed potent anti-tumor, anti-metastatic, and anti-angiogenic effects.
Article
Microbiology
Anna Claudia Silva, Daniel Clemente de Moraes, Denilson Costa do Carmo, Giselle Cristina Casaes Gomes, A. Ganesan, Rosangela Sabbatini Capella Lopes, Antonio Ferreira-Pereira, Claudio Cerqueira Lopes
Summary: Azoles are the main antifungal drugs used to treat invasive candidiasis, but their efficacy is limited by fungal resistance mechanisms like overexpression of efflux pumps. A potential strategy to overcome this resistance is to inhibit the efflux process. This study aimed to synthesize altissimacoumarin D and its analogues to evaluate their ability to reverse the resistance phenotype of Candida albicans.
Article
Chemistry, Organic
Paulo Eliandro da Silva Junior, Shaiani Maria Gil de Melo, Murilo Helder de Paula, Ricardo Vessecchi, Till Opatz, James E. H. Day, A. Ganesan, Flavio da Silva Emery
Summary: This article discusses the reactivity of 6-azaindazole and 2,6-naphthyridine, which are important in fragment-based drug discovery. The article introduces selective functionalization methods for pyridone and pyrazole, as well as a new method for selective functionalization of heterocycle 1.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Review
Chemistry, Multidisciplinary
Timothe Maujean, Nicolas Girard, A. Ganesan, Mihaela Gulea, Dominique Bonnet
