Article
Biochemistry & Molecular Biology
Yamei Hu, Fangfang Liu, Xuechao Jia, Penglei Wang, Tingxuan Gu, Hui Liu, Tingting Liu, Huifang Wei, Hanyong Chen, Jiuzhou Zhao, Ran Yang, Yingying Chen, Zigang Dong, Kangdong Liu
Summary: A novel STAT3 inhibitor, periplogenin, was identified in this study, showing significant inhibition of ESCC growth in vitro and in vivo. It has the potential to be utilized for the treatment and prevention of ESCC.
Article
Oncology
Esther P. Jane, Daniel R. Premkumar, Dhivyaa Rajasundaram, Swetha Thambireddy, Matthew C. Reslink, Sameer Agnihotri, Ian F. Pollack
Summary: This study demonstrates that targeting aurora kinases with tozasertib can effectively inhibit cell growth and migration in high-grade glioma cell lines, leading to cell death. However, sustained exposure to tozasertib can result in drug resistance, with upregulation of PDK genes playing a crucial role in the emergence of resistance.
MOLECULAR ONCOLOGY
(2022)
Article
Cell Biology
Xinning Liu, Yanan Jiang, Hao Zhou, Xiaokun Zhao, Mingzhu Li, Zhuo Bao, Zitong Wang, Chenyang Zhang, Zhenliang Xie, Jimin Zhao, Zigang Dong, Kangdong Liu, Zhiping Guo
Summary: Esophageal squamous cell carcinoma (ESCC), a highly fatal upper gastrointestinal cancer, can be suppressed by dasabuvir, an FDA-approved drug for hepatitis C virus (HCV) treatment. Dasabuvir inhibits ESCC cell growth in a dose and time-dependent manner, arresting cell cycle progression. In vivo validation using patient-derived xenograft tumor models further confirmed the anti-tumor activity. Mechanistically, dasabuvir acts as a ROCK1 inhibitor, blocking the ROCK1/ERK signaling pathway and downregulating CDK4 and cyclin D1 expression.
CELL DEATH & DISEASE
(2023)
Article
Immunology
Ankit Uniyal, Anagha Gadepalli, Ajay Modi, Vinod Tiwari
Summary: Chronic pain is a burdensome disorder affecting millions of people worldwide, and recent studies have revealed the important role of kinesin nanomotors. In an animal model, the aurora kinase inhibitor tozasertib can alleviate acute inflammatory pain and suppress hypersensitivity to different stimuli. Further investigations demonstrate that tozasertib can also attenuate oxidative stress and immune cell activation induced by chronic pain. These findings suggest that tozasertib exerts its anti-nociceptive effects by inhibiting the aurora kinase-mediated signaling.
INFLAMMOPHARMACOLOGY
(2022)
Review
Allergy
Peter Valent, Cem Akin, Karin Hartmann, Andreas Reiter, Jason Gotlib, Karl Sotlar, Wolfgang R. Sperr, Lina Degenfeld-Schonburg, Dubravka Smiljkovic, Massimo Triggiani, Hans-Peter Horny, Michel Arock, Stephen J. Galli, Dean D. Metcalfe
Summary: Mast cell activation plays a crucial role in allergic reactions, inflammatory states, and mast cell activation syndromes. While there is currently no treatment approach to eradicate mast cells, long-term use of drugs that inhibit KIT function may lead to a decrease in tissue mast cells and improvement in symptoms. For patients with KIT D816V-positive mastocytosis, effective KIT inhibitors like avapritinib may be used for mast cell eradication, but potential side effects need to be considered.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Meng-di Dai, Yue-liang Wang, Jun Fan, Yang Dai, Yin-chun Ji, Yi-ming Sun, Xia Peng, Lan-lan Li, Yu-ming Wang, Wen-hu Duan, Jian Ding, Jing Ai
Summary: DW14383 is a promising selective irreversible pan-FGFR inhibitor with pan-tumor spectrum potential in FGFR1-4 aberrant cancers, which has the potential to overcome compensatory activation among FGFR1-4.
ACTA PHARMACOLOGICA SINICA
(2021)
Article
Pharmacology & Pharmacy
Peiran Song, Gang Bai, Shingpan Chan, Tao Zhang, Linjiang Tong, Yi Su, Yanyan Shen, Yi Chen, Yingqiang Liu, Mengzhen Lai, Yi Ning, Haotian Tang, Yan Fang, Yi Chen, Ke Ding, Jian Ding, Hua Xie
Summary: This study demonstrated that the novel drug ASK120067 exhibited potent anti-tumor activity against B-/T-cell malignancies by targeting BTK/ITK. It inhibited the phosphorylation of BTK and ITK, induced apoptosis in B-lymphoma cells, and caused growth arrest in T-cell leukemia cells. Oral administration of ASK120067 also led to significant tumor regression in xenograft models.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Oncology
Yaxing Wei, Wenjie Wu, Yanan Jiang, Hao Zhou, Yin Yu, Lili Zhao, Xiangyu Wu, Xuebo Lu, Qiang Yuan, Zitong Wang, Zigang Dong, Luyun He, Jimin Zhao, Kangdong Liu
Summary: Nuplazid may suppress ESCC progression by targeting PAK4.
BRITISH JOURNAL OF CANCER
(2022)
Article
Toxicology
Maik Schuler, Lindsay Tomlinson, Michael Homiski, Jennifer Cheung, Yutian Zhan, Stephanie Coffing, Maria Engel, Elizabeth Rubitski, Gary Seitis, Katherine Hales, Andrew Robertson, Saurabh Vispute, Jon Cook, Zaher Radi, Brett Hollingshead
Summary: The EpiDerm in vitro micronucleus assay is suitable for the hazard identification of aneugens. Results showed positive micronucleus responses for all aneugens tested, while in vivo minipig studies did not show a response to aneugens, indicating that the barrier function of minipig skin protects from the effects of aneugens in vivo. Further studies are needed to refine the understanding of aneugen risk management.
TOXICOLOGICAL SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Meiqing Li, Danyi Lu, Yulian Cheng, Chunlei Wu, Jianchao Zhang, Wenli Shi, Zhihao Ding, Yanyan Li, Binghua Cheng, Xian Lin, Ximing Shao, Hongchang Li, Lijing Fang, Ke Liu, Wu Su
Summary: The newly developed drug molecule PIP-Ht targets the Aurora A gene promoter and shows potent inhibitory effects on tumor cell growth and proliferation in vitro and in vivo, demonstrating potential as an effective candidate for cancer treatment.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Plant Sciences
Jihee Hong, Dasom Gwon, Chang-Young Jang
Summary: Ginsenoside Rg1 reduces cancer cell proliferation by inhibiting Haspin kinase activity and H3T3ph, leading to decreased levels of Aurora B at the centromere.
JOURNAL OF GINSENG RESEARCH
(2022)
Article
Chemistry, Medicinal
Danli Zhou, Yingying Zuo, Zhengying Pan
Summary: This study reports the development of cereblon-recruiting ITK proteolysis targeting chimeras based on a structure-based design strategy, which holds great therapeutic potential for human autoimmune diseases and T-cell malignant lymphomas. Two representative compounds, 23 and 28, demonstrated potent ITK degradation and IL-2 inhibition activities in Jurkat cells. Global proteomic profiling assays confirmed the high selectivity of compounds 23 and 28 as ITK degraders. Compound 28 exhibited efficient, rapid, and prolonged ITK degradation in mice, along with significant suppression of IL-2 secretion. It is the first effective and highly selective ITK degrader, serving as a valuable tool compound for further investigation of ITK degradation in human diseases.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Oncology
Yajing Xing, Weikai Guo, Min Wu, Jiuqing Xie, Dongxia Huang, Pan Hu, Miaoran Zhou, Lin Zhang, Qiansen Zhang, Peili Wang, Xin Wang, Guixue Wang, Huangan Wu, Cili Zhou, Yihua Chen, Mingyao Liu, Zhengfang Yi, Zhenliang Sun
Summary: Researchers have identified a small molecule compound named WK500B that can block the inhibition of BCL6, reactivate target genes, kill DLBCL cells, and display strong anti-tumor effects in animal models. Therefore, WK500B holds promise as an effective orally available therapeutic agent for DLBCL.
Article
Multidisciplinary Sciences
Rong-quan Xiao, Ting Ran, Qi-xuan Huang, Guo-sheng Hua, Da-meng Fan, Jia Yi, Wen Liu
Summary: JMJD6 is a potential therapeutic target in cancer treatment, and iJMJD6, a specific inhibitor of JMJD6, has been found to effectively suppress cancer cell proliferation, migration, and invasion. It represses oncogene expression and exhibits synergistic effects in combination with other drugs, providing a new avenue for cancer therapy.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Oncology
Xixi Zhao, Yongkun Wei, Yu-Yi Chu, Yintao Li, Jung-Mao Hsu, Zhou Jiang, Chunxiao Liu, Jennifer L. Hsu, Wei-Chao Chang, Riyao Yang, Li-Chuan Chan, Jingkun Qu, Shuqun Zhang, Haoqiang Ying, Dihua Yu, Mien-Chie Hung
Summary: This study reveals the role of CK2 in immunosuppression by phosphorylation and stabilization of PD-L1, and suggests CK2 inhibition as a potential immunotherapeutic approach for treating cancer.
Article
Allergy
Ze-Lang Cai, Jia-Jie Chen, Zhen Zhang, Yi-Bo Hou, Yong-shen He, Jin-Lyu Sun, Kunmei Ji
CLINICAL AND TRANSLATIONAL ALLERGY
(2019)
Article
Oncology
Jia-Jie Chen, Li-Na Zhang, Nan Cai, Zhen Zhang, Kunmei Ji
Article
Medicine, Research & Experimental
Ze-Lang Cai, Zhen Zhang, Wen-Li Luo, Yi-Bo Hou, Yong-Shen He, Jia-Jie Chen, Kunmei Ji
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
(2019)
Article
Medicine, Research & Experimental
Yi-Bo Hou, Kunmei Ji, Yue-Tong Sun, Li-Na Zhang, Jia-Jie Chen
JOURNAL OF TRANSLATIONAL MEDICINE
(2019)
Article
Medicine, Research & Experimental
Jia-Jie Chen, Yong-Shen He, Xiao-Jun Zhong, Ze-Lang Cai, Yan-Si Lyu, Zhen-Fu Zhao, Kunmei Ji
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
(2020)
Article
Immunology
Yi-Bo Hou, Li-Na Zhang, Hui-Na Wang, Zhen-Fu Zhao, Yue-Tong Sun, Kunmei Ji, Jia-Jie Chen
INTERNATIONAL IMMUNOPHARMACOLOGY
(2020)
Article
Medicine, Research & Experimental
Hui-Na Wang, Kunmei Ji, Li-Na Zhang, Chu-Chu Xie, Wei-Yong Li, Zhen-Fu Zhao, Jia-Jie Chen
Summary: The study demonstrates the involvement of c-Fos in mast cell activation and the potential of the c-Fos/AP1 inhibitor T-5224 in alleviating IgE-mediated allergic responses. This suggests a promising strategy for targeting mast cell activation to treat allergic diseases.
JOURNAL OF TRANSLATIONAL MEDICINE
(2021)
Article
Allergy
Jiajie Chen, Zelang Cai, Dingding Fan, Jiayu Hu, Yibo Hou, Yongsen He, Zhen Zhang, Zhenfu Zhao, Pan Gao, Wanzhen Hu, Jinlyu Sun, Jiang Li, Kunmei Ji
Summary: This study aimed to assemble a chromosome-level genome and transcriptome of the house dust mite, Dermatophagoides farinae, in order to identify novel allergens. Results showed a significant reduction in bacterial DNA content, correction of genome size, and increased contig N50 compared to the draft genome. The assembled genome contained 33 canonical allergens and 2 novel allergens, with 2 allergens being identified through binding with HDM allergic-sera.
WORLD ALLERGY ORGANIZATION JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Hui-Na Wang, Qiu-An Xiang, Hao-Hui Lin, Jie-Ning Chen, Wen-Jie Guo, Wan-Meng Guo, Xiang-Ning Yue, Zhen-Fu Zhao, Kunmei Ji, Jia-Jie Chen
Summary: This study demonstrates the inhibitory effect of 4-MU on mast cell activation both in vitro and in vivo. 4-MU suppresses the release of histamine and beta-hexosaminidase, reduces cytomorphological elongation and F-actin reorganization, and down-regulates the phosphorylation of several signaling proteins. Furthermore, 4-MU attenuates allergic reactions and decreases the secretion of histamine and IL4 in mouse models. These findings suggest that 4-MU may represent a new therapeutic strategy for IgE-mediated allergic conditions.
Article
Biochemistry & Molecular Biology
Zi-Wen Zhou, Kunmei Ji, Xue-Yan Zhu, Xin-Ying Wu, Ruo-Tong Lin, Chu-Chu Xie, Ze-Lang Cai, Jia-Jie Chen
Summary: In this study, the natural isoflavone formononetin (FNT) was found to inhibit IgE-mediated mast cell activation and reduce allergic inflammation. FNT suppressed the release of inflammatory factors, histamine, and beta-hexosaminidase, and inhibited NF-kappa B and MAPK activity in mast cells. FNT also induced degradation and ubiquitination of the high-affinity IgE receptor, suggesting its potential as a therapeutic target for allergic diseases.
Article
Biochemistry & Molecular Biology
Chu-Chu Xie, Bo-Ping Zhang, Hui-Na Wang, Wei-Yong Li, Ze-Lang Cai, Yong He, Kunmei Ji, Jia-Jie Chen
Summary: This study found that dihydrocoumarin (DHC), a food flavoring agent derived from Melilotus officinalis, can suppress mast cell (MC) activation and alleviate IgE-mediated allergic reactions. DHC acts by inhibiting multiple signaling pathways and reducing MC degranulation and morphological changes associated with MC activation.