Article
Oncology
Fushun Fan, Pei Liu, Rudi Bao, Jian Chen, Minhua Zhou, Zhenxian Mo, Yaru Ma, Haiqi Liu, Yiping Zhou, Xiong Cai, Changgeng Qian, Xinjian Liu
Summary: BEBT-908, a dual PI3K/HDAC inhibitor, effectively inhibits tumor cell growth and enhances the efficacy of anti-PD1 therapy in mice by inducing immunogenic ferroptosis. It also promotes a proinflammatory tumor microenvironment and activates host antitumor immune responses, potentiating immune checkpoint blockade therapy. Mechanistically, BEBT-908-induced ferroptosis upregulates MHC class I and activates endogenous IFN gamma signaling in cancer cells via the STAT1 signaling pathway.
Article
Immunology
Mahdieh Mehrpouri, Atieh Pourbagheri-Sigaroodi, Davood Bashash
Summary: This article outlines the role of epigenetic modulations, particularly histone deacetylases, in hematologic malignancies and their therapeutic potential. Research suggests that HDACs play a significant role in hematopoiesis and the development of blood cancers.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Marta Halasa, Kamila Adamczuk, Grzegorz Adamczuk, Syeda Afshan, Andrzej Stepulak, Marek Cybulski, Anna Wawruszak
Summary: N-ε-lysine acetylation/deacetylation is a common post-translational modification regulated by histone acetyltransferases and histone deacetylases, influencing the properties and functions of histones and non-histone proteins, including transcription factors that alter cell signaling pathways and impact cancer progression. HDACs play a significant role in deacetylating targets, leading to the regulation of proteins involved in cell cycle and apoptosis, ultimately affecting tumor growth, invasion, and drug resistance. This review highlights the clinical importance of epigenetic modifications as a potential therapeutic target in cancer treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Pharmacology & Pharmacy
Edoardo Parrella, Vanessa Porrini, Ilaria Scambi, Michele M. Gennari, Cristina Gussago, Oluwamolakun Bankole, Marina Benarese, Raffaella Mariotti, Marina Pizzi
Summary: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with no cure. Recent research has shown that epigenetic mechanisms, such as histone hypoacetylation and abnormal activation of NF-kappa B/RelA, play a role in ALS. The combination of low doses of the AMP-activated kinase (AMPK)-sirtuin 1 pathway activator resveratrol and histone deacetylase (HDAC) inhibitors can correct the pathological acetylation state and have a positive effect on disease onset, survival, and motor neurons degeneration.
FRONTIERS IN PHARMACOLOGY
(2022)
Editorial Material
Microbiology
Tom Boissavy, Dante Rotili, Thomas Mouveaux, Emmanuel Roger, El Moukthar Aliouat, Christine Pierrot, Sergio Valente, Antonello Mai, Mathieu Gissot
Summary: Toxoplasmosis is a significant health issue for immune-deficient individuals and newborns of infected mothers. New compounds with potent anti-parasitic activity have been discovered, which can serve as therapeutic targets for the treatment of toxoplasmosis.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Chemistry, Medicinal
Marcel K. W. Mackwitz, Eva Hesping, Korina Eribez, Andrea Schoeler, Yevgeniya Antonova-Koch, Jana Held, Elizabeth A. Winzeler, Katherine T. Andrews, Finn K. Hansen
Summary: This study reports on a new peptoid-based HDAC inhibitor with dual-stage antiplasmodial activity, showing potential activity against malaria parasites and selectivity for human cells. These data provide a foundation for future improvements to these dual-stage inhibitors as potential drug leads for malaria.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Justine S. Habibian, Matthew J. Bolino, Bradley S. Ferguson
Summary: Skeletal muscle differentiation requires the activation of satellite cells to proliferate, differentiate, and fuse. This process is regulated by myogenic transcription factors, which are tightly controlled by intracellular signaling pathways, including the protein kinase D (PKD) family. In this study, the researchers found that inhibiting class I histone deacetylases (HDACs), specifically HDAC8, attenuated PKD phosphorylation in skeletal muscle cells, suggesting that HDAC8 may function as a feedback regulator of PKD phosphorylation during muscle differentiation.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Review
Biochemistry & Molecular Biology
Anton Fruhauf, Franz-Josef Meyer-Almes
Summary: HDACs play a role in many diseases, and the hydroxamate group in HDACis may cause toxic side effects, leading to exploration of non-hydroxamic HDACis. These new inhibitors have alternative ZBGs to replace the hydroxamate group, maintaining high potency and high selectivity.
Review
Medical Laboratory Technology
Jehan Mohammad Nazri, Katerina Oikonomopoulou, Elvin D. de Araujo, Dziyana Kraskouskaya, Patrick T. Gunning, Vinod Chandran
Summary: Psoriasis and psoriatic arthritis (PsA) are inflammatory diseases that affect the skin and musculoskeletal system. Current treatments for these conditions are not fully effective, leading to a reduced quality of life for patients. Histone deacetylase (HDAC) inhibitors, originally investigated as anti-cancer agents, have shown promise as a new anti-inflammatory treatment for inflammatory diseases. However, more research is needed to determine their effectiveness for PsA patients. This review provides an overview of psoriatic disease, HDACs, and discusses the potential use of HDAC inhibitors in managing persistent inflammation in psoriatic disease.
CRITICAL REVIEWS IN CLINICAL LABORATORY SCIENCES
(2023)
Review
Pharmacology & Pharmacy
Eleftherios Spartalis, Konstantinos Kotrotsios, Dimosthenis Chrysikos, Michael Spartalis, Stavroula A. Paschou, Dimitrios Schizas, Konstantinos Tsamakis, Dimitrios Dimitroulis, Theodore Troupis, Nikolaos Nikiteas
Summary: The study evaluates the role of HDACIs in PTC treatment and outlines the current trends in research. While HDACIs show promising anti-cancer effects on PTC cell lines, they have not shown significant responses in clinical trials. Further research is needed to explore their potential as an additional treatment modality.
CURRENT PHARMACEUTICAL DESIGN
(2021)
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)
Review
Chemistry, Multidisciplinary
Siddhartha Das Pramanik, Amit Kumar Halder, Ushmita Mukherjee, Dharmendra Kumar, Yadu Nandan Dey, R. Mogana
Summary: This review examines the role of HDACs in cancer treatment. While clinical trials with HDACi as monotherapy have had mixed results, combination therapy with other anticancer drugs has shown synergistic effects, increasing efficacy and decreasing toxicity.
FRONTIERS IN CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Bartosz Bieszczad, Damian Garbicz, Marta Switalska, Marta K. Dudek, Dawid Warszycki, Joanna Wietrzyk, Elzbieta Grzesiuk, Adam Mieczkowski
Summary: In this study, a library of 19 analogues of Vorinostat was developed and tested for their HDAC inhibition and cytotoxic effects on cancer and normal cell lines. Three compounds based on dibenzo[b,f]azocin-6(5H)-one, 11,12-dihydrodibenzo[b,f]azocin-6(5H)-one, and benzo[b]naphtho[2,3-f][1,5]diazocine-6,14(5H,13H)-dione scaffolds showed better HDAC inhibition and lower IC50 values in leukemic and lymphoma cell lines compared to Vorinostat. These compounds exhibited higher activity and selectivity against specific cancer cell lines and a correlation between HDAC inhibition and cytotoxic effects was observed.
Article
Chemistry, Medicinal
Eva Hesping, Ming Jang Chua, Marc Pflieger, Yunan Qian, Lilong Dong, Prabhakar Bachu, Ligong Liu, Thomas Kurz, Gillian M. Fisher, Tina S. Skinner-Adams, Robert C. Reid, David P. Fairlie, Katherine T. Andrews, Alain-Dominique J. P. Gorse
Summary: Malaria, a deadly disease caused by Plasmodium parasites, claims a large number of lives every year. Due to the increasing resistance of the parasites to current antimalarials, there is a need for new drugs. Researchers have developed quantitative structure-activity relationship models to predict the antiplasmodial activity of hydroxamate-based HDAC inhibitors and identified three compounds with strong activity against the parasites.
ACS INFECTIOUS DISEASES
(2022)
Article
Biochemistry & Molecular Biology
Thais Oliveira, Evan Hermann, Daniel Lin, Winyoo Chowanadisai, Elizabeth Hull, McKale Montgomery
Summary: Epithelial-to-mesenchymal transition (EMT) is a crucial process in development and wound healing, but it can also contribute to the progression and spread of aggressive tumors in cancer, as well as increase resistance to therapy. This study used the SW13 cell line to investigate the connection between iron metabolism and EMT, finding that HDAC inhibitor treatment led to increased iron accumulation, reduced expression of iron export proteins, and enhanced sensitivity to a form of iron-mediated cell death called ferroptosis. These findings suggest potential implications for improving iron-targeted chemotherapeutic strategies in cancer treatment.