Article
Chemistry, Medicinal
Seong-Jun Park, Sang Hoon Joo, Naeun Lee, Won-Jun Jang, Ji Hae Seo, Chul-Ho Jeong
Summary: The study demonstrated that the selective inhibitor of HDAC6, ACY-241, significantly reduced the viability of erlotinib-resistant pancreatic cancer cells by hyperacetylating the HDAC6 substrate alpha-tubulin. Synergistic anticancer effects were observed when ACY-241 was combined with erlotinib, inducing autophagy and cell death by regulating AKT-mTOR activity and phospho-AMPK signaling pathways.
ARCHIVES OF PHARMACAL RESEARCH
(2021)
Article
Oncology
Jennifer E. Amengual, Jennifer K. Lue, Helen Ma, Renee Lichtenstein, Bijal Shah, Serge Cremers, Simon Jones, Ahmed Sawas
Summary: ACY-1215, an oral selective HDAC6 inhibitor, was safe in patients with relapsed and refractory lymphoid malignancies and led to disease stabilization in half of the evaluable patients.
Article
Biochemistry & Molecular Biology
Ji Yoon Kim, Seung Yoon Han, Jung Yoo, Go Woon Kim, Yu Hyun Jeon, Sang Wu Lee, Jongsun Park, So Hee Kwon
Summary: This study evaluated the synergistic anticancer effects of PCI-34051 and ACY-241 in ovarian cancer. The combination treatment effectively suppressed cell proliferation, enhanced apoptosis, and suppressed cell migration. The expression of pro-apoptotic proteins was upregulated, while the expressions of anti-apoptotic proteins and metastasis-associated proteins were downregulated in the combination treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Shunda Li, Chunlong Zhao, Guozhen Zhang, Qifu Xu, Qian Liu, Wei Zhao, C. James Chou, Yingjie Zhang
Summary: The novel pyrrolo[2,3-d]pyrimidine-based HDAC inhibitors demonstrated potent inhibitory activities and selectivities against HDAC6, showing superior antiproliferative activity against human multiple myeloma cell lines while maintaining low cytotoxicity. In addition, one representative compound showed good metabolic stability and in vivo anti-multiple myeloma potency in a xenograft model.
BIOORGANIC CHEMISTRY
(2021)
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)
Article
Biochemistry & Molecular Biology
Sang Wu Lee, Soo-Keun Yeon, Go Woon Kim, Dong Hoon Lee, Yu Hyun Jeon, Jung Yoo, So Yeon Kim, So Hee Kwon
Summary: The HDAC6-selective inhibitor A452 has been shown to overcome bortezomib resistance in multiple myeloma by decreasing the activation of resistant markers and synergistically inhibiting cancer cell growth when used in combination with other drugs. This discovery highlights the potential of A452 as a promising therapy for bortezomib-chemoresistant multiple myeloma patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
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
Chemistry, Medicinal
Nabanita Nawar, Shazreh Bukhari, Ashley A. Adile, Yujin Suk, Pimyupa Manaswiyoungkul, Krimo Toutah, Olasunkanmi O. Olaoye, Yasir S. Raouf, Abootaleb Sedighi, Harsimran Kaur Garcha, Muhammad Murtaza Hassan, William Gwynne, Johan Israelian, Tudor B. Radu, Mulu Geletu, Ayah Abdeldayem, Justyna M. Gawel, Aaron D. Cabral, Chitra Venugopal, Elvin D. de Araujo, Sheila K. Singh, Patrick T. Gunning
Summary: Through a second-generation structure-activity relationship study, the selective HDAC6 inhibitor NN-390 was designed and evaluated, showing therapeutic potential in the treatment of metastatic Group 3 MB and demonstrating high selectivity and potency in targeting cells in vitro.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Oncology
Mark M. Awad, Yvan Le Bruchec, Brian Lu, Jason Ye, JulieAnn Miller, Patrick H. Lizotte, Megan E. Cavanaugh, Amanda J. Rode, Calin Dan Dumitru, Alexander Spira
Summary: This study investigated the combination of the HDAC6 inhibitor ACY-241 and nivolumab in previously treated advanced NSCLC patients, finding an MTD of 360 mg for ACY-241 with manageable toxicity. The most common grade ≥3 treatment-related adverse events were dyspnea and pneumonia, while some level of efficacy was observed at different doses.
FRONTIERS IN ONCOLOGY
(2021)
Article
Biology
Xingang Liu, Wenying Yan, Songsong Wang, Ming Lu, Hao Yang, Xu Chai, He Shi, Yang Zhang, Qingzhong Jia
Summary: A multi-layer virtual screening workflow was established to screen compounds with inhibitory activity against HDAC6 and anti-tumor cell proliferation. The screened compounds showed nanomolar inhibitory activity and anti-proliferative activities against tumor cells, providing novel scaffolds for subsequent anti-tumor drug design based on HDAC6 target.
COMPUTERS IN BIOLOGY AND MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Yunpeng Zhao, Tao Liang, Xuben Hou, Hao Fang
Summary: Histone deacetylation plays crucial roles in chromatin remodeling and gene expression, and aberrant modification can lead to various diseases. HDAC6, a critical member of the HDAC family, serves as a key modulator in many physiological processes, and abnormal expression is linked to cancer, neurodegeneration, and other diseases. Recent advances have been made in the physiological functions, protein structure, and development of HDAC6 selective inhibitors.
CURRENT MEDICINAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Tung-Yun Wu, Michael Chen, I. -Chung Chen, Yi-Jou Chen, Che-Yi Chen, Chang-Hung Wang, Jing-Jy Cheng, Kunal Nepali, Kuo-Hsiang Chuang, Jing-Ping Liou
Summary: In this study, a novel therapeutic strategy was proposed that not only kills tumor cells but also destroys the tumor microenvironment and enhances anti-cancer immunity.
JOURNAL OF ADVANCED RESEARCH
(2023)
Article
Chemistry, Medicinal
Fengling Liu, Chunxi Liu, Qipeng Chai, Chunlong Zhao, Hongwei Meng, Xia Xue, Tso-pang Yao, Yingjie Zhang
Summary: In our previous research, a compound named 1 showed significant anti-tumor activity due to its HDAC inhibitory and NO-donating properties. Further study revealed that compound 1 could increase acetyl histones and acetyl & alpha;-tubulin levels by irreversibly inhibiting class I HDACs and HDAC6. Modification of compound 1 led to the development of compound 4, which selectively and irreversibly inhibited intracellular HDAC6 and exhibited improved therapeutic index compared to ACY-241.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Yajie Guo, Xi Wang, Zhenzhen Wang, Longfei Mao, Jiahao Wang, Lizeng Peng, Guiqing Xu
Summary: By designing and synthesizing a series of new pomalidomide derivatives containing urea moieties, we discovered that some of them displayed potent anti-tumor ability, with compound 5d showing the strongest effects in inhibiting cell growth and inducing cell death.
Article
Biochemistry & Molecular Biology
Mussa Yussuf Khamis, Hui-Pan Wu, Qin Ma, Yi-Han Li, Li-Ying Ma, Xin-Hui Zhang, Hong-Min Liu
Summary: Tumor immunotherapy is a focus of current scientific and clinical research, with combinatorial therapeutic strategies showing promise in slowing down disease progression and improving sensitivity to immunomodulatory agents. Combinations of HDAC6is with other agents may be potential strategies to treat tumor immune diseases in the future, reducing side effects and enhancing efficacy.
BIOORGANIC CHEMISTRY
(2021)