Article
Oncology
Arthur Branstrom, Liangxian Cao, Bansri Furia, Christopher Trotta, Marianne Santaguida, Jason D. Graci, Joseph M. Colacino, Balmiki Ray, Wencheng Li, Josephine Sheedy, Anna Mollin, Shirley Yeh, Ronald Kong, Richard Sheridan, John D. Baird, Kylie O'Keefe, Robert Spiegel, Elizabeth Goodwin, Suzanne Keating, Marla Weetall
Summary: Blocking DHODH using Emvododstat has the potential to inhibit the progression of acute myeloid leukemia (AML) by inducing differentiation and cytotoxicity. It has broad activity against various AML cell lines and patient-derived xenograft models. Emvododstat acts rapidly and reversibly by inhibiting DHODH, making it a promising therapeutic option for AML.
FRONTIERS IN ONCOLOGY
(2022)
Article
Pharmacology & Pharmacy
Anna Luganini, Giulia Sibille, Barbara Mognetti, Stefano Sainas, Agnese Chiara Pippione, Marta Giorgis, Donatella Boschi, Marco L. Lolli, Giorgio Gribaudo
Summary: The new generation inhibitor MEDS433 shows strong antiviral activity against HSV-1 and HSV-2 in vitro by preventing the accumulation of viral genomes and reducing late gene expression, indicating its mechanism of action as inhibition of DHODH activity.
ANTIVIRAL RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Grzegorz Adamczuk, Ewelina Humeniuk, Magdalena Iwan, Dorota Natorska-Chomicka, Kamila Adamczuk, Agnieszka Korga-Plewko
Summary: Leflunomide has been shown to have cytotoxicity against RPMI 8226 cell line in a DHODH- and mitochondria-independent mechanism. Teriflunomide, an active metabolite of leflunomide, induces G2/M phase cell cycle arrest and apoptosis in a mitochondria-independent manner, suggesting a unique cytotoxic mechanism. Moreover, teriflunomide does not affect cellular thiol levels, indicating a distinct pathway of toxicity.
Article
Pharmacology & Pharmacy
Mingli Gong, Yiqing Yang, Yi Huang, Tianyu Gan, Yue Wu, Hongying Gao, Qianqian Li, Jianhui Nie, Weijin Huang, Youchun Wang, Rong Zhang, Jin Zhong, Fei Deng, Yu Rao, Qiang Ding
Summary: RYL-634 and its derivatives show effective inhibition against EBOV infection, with the new derivative RYL-687 demonstrating the lowest IC50 and being almost 6 times more potent than remdesivir. These quinolone-derived compounds are promising therapeutic candidates against EBOV infection.
ANTIVIRAL RESEARCH
(2021)
Article
Cell & Tissue Engineering
Toru Kondo
Summary: The study demonstrates that the DHODH inhibitor BRQ induces differentiation in mouse PSCs, preventing teratoma formation, while showing low toxicity to normal cells. This suggests that DHODH inhibitors like BRQ could be crucial for successful PSC-based therapy.
Article
Oncology
Zhi-Zhou Shi, Xin Jin, Wen-Ting Li, Hao Tao, Sheng-Jie Song, Ze-Wen Fan, Wen Jiang, Jian-Wei Liang, Jie Bai
Summary: DHODH is overexpressed in various cancers and plays an oncogenic role by enhancing cell proliferation and suppressing cell death. DHODH may serve as a potential therapeutic target for cancer treatment.
TRANSLATIONAL CANCER RESEARCH
(2023)
Article
Chemistry, Medicinal
Xia Zhou, Kun Gou, Jing Xu, Lunan Jian, Yuan Luo, Chungen Li, Xinqi Guan, Jiahao Qiu, Jiao Zou, Yu Zhang, Xi Zhong, Ting Zeng, Yue Zhou, Yuzhou Xiao, Xinyu Yang, Weijie Chen, Ping Gao, Chunqi Liu, Yang Zhou, Lei Tao, Xingchen Liu, Xiaobo Cen, Qiang Chen, Qingxiang Sun, Youfu Luo, Yinglan Zhao
Summary: Compound w2 is a promising hDHODH inhibitor for the treatment of IBD, showing better therapeutic effects than existing drugs.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Chemistry, Medicinal
Vivek K. Vyas, Tanvi Shukla, Manmohan Sharma
Summary: This article provides a review on drug-resistant malaria, focusing on the discovery and identification of selective P. falciparum dihydroorotate dehydrogenase inhibitors as antimalarial agents.
FUTURE MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Stefano Sainas, Marta Giorgis, Paola Circosta, Valentina Gaidano, Davide Bonanni, Agnese C. Pippione, Renzo Bagnati, Alice Passoni, Yaqi Qiu, Carina Florina Cojocaru, Barbara Canepa, Alessandro Bona, Barbara Rolando, Mariia Mishina, Cristina Ramondetti, Barbara Buccinna, Marco Piccinini, Mohammad Houshmand, Alessandro Cignetti, Enrico Giraudo, Salam Al-Karadaghi, Donatella Boschi, Giuseppe Saglio, Marco L. Lolli
Summary: Compound 1 is a potent hDHODH inhibitor that induces AML cell differentiation and shows good metabolic stability and safety in mice. Compound 17, on the other hand, exhibits stronger activity in inducing AML cell differentiation, apoptosis, and lower cytotoxicity towards non-AML cells.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Shuntaro Miyake, Seiji Masuda
Summary: Intracellular and intercellular signaling networks are essential for cellular homoeostasis and are reflected in nuclear mRNA dynamics. In this study, the researchers discovered that certain inhibitors cause the accumulation of nuclear poly(A)(+) RNA, particularly near nuclear speckles. The study also revealed the involvement of ATM, a kinase that regulates DNA double-strand breaks and nucleolar stress, in this phenomenon. The findings provide new insights into the relationship between mitochondrial respiratory-chain functions, pyrimidine metabolism, and nuclear RNA metabolism.
Article
Infectious Diseases
Maria J. G. T. Vehreschild, Petar Atanasov, Kateryna Yurko, Cristian Oancea, Georgi Popov, Valentina Smesnoi, Gheorghe Placinta, Hella Kohlhof, Daniel Vitt, Evelyn Peelen, Jelena Mihajlovic, Andreas R. Muehler
Summary: Vidofludimus calcium has been shown to be safe and well tolerated in patients with COVID-19, with a shorter time to clinical improvement and reduced risk of invasive ventilation, making it a promising treatment option for the disease.
INFECTIOUS DISEASES AND THERAPY
(2022)
Article
Biochemistry & Molecular Biology
Bimala Malla, Agustin Liotta, Helena Bros, Rebecca Ulshoefer, Friedemann Paul, Anja E. Hauser, Raluca Niesner, Carmen Infante-Duarte
Summary: TFN preserves neuronal functionality and prevents morphological and motility alterations of mitochondria under oxidative stress conditions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Pharmacology & Pharmacy
Hardeep Kaur, Phulen Sarma, Anusuya Bhattacharyya, Saurabh Sharma, Neeraj Chhimpa, Manisha Prajapat, Ajay Prakash, Subodh Kumar, Ashutosh Singh, Rahul Singh, Pramod Avti, Prasad Thota, Bikash Medhi
Summary: DHODH inhibitors have shown promise as antiviral agents against various viruses, including SARS-CoV-2. Studies have shown favorable binding of leflunomide to MPro and spike: ACE2 interface, as well as its involvement in COVID-19 related pathways. Clinical studies have demonstrated the benefits of leflunomide in reducing viral shedding duration, hospital stay duration, and infection severity.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Oncology
Rui Jin, Boxuan Liu, Xiuju Liu, Yijian Fan, Wei Peng, Chunzi Huang, Adam Marcus, Gabriel Sica, Melissa Gilbert-Ross, Yuan Liu, Wei Zhou
Summary: Leflunomide treatment effectively suppresses the growth of LKB1-inactivated tumors through multiple mechanisms, while also preventing cancer metastasis at distant sites.
MOLECULAR CANCER THERAPEUTICS
(2021)
Article
Pharmacology & Pharmacy
James F. Demarest, Maryline Kienle, RuthMabel Boytz, Mary Ayres, Eun Jung Kim, J. J. Patten, Donghoon Chung, Varsha Gandhi, Robert A. Davey, David B. Sykes, Nadim Shohdy, John C. Pottage Jr, Vikram S. Kumar
Summary: The need for new drug treatments for COVID-19, caused by SARS-CoV-2, is highlighted due to the virus's continued evolution. One potential strategy is the combination of BRQ and DPY to enhance depletion of the cellular pyrimidine nucleotide pool and show antiviral activity against SARS-CoV-2 variants.
ANTIVIRAL RESEARCH
(2022)
Article
Oncology
Zhen Dong, Hongjuan Cui
SEMINARS IN CANCER BIOLOGY
(2019)
Review
Cell Biology
Zhen Dong, Hongjuan Cui
Article
Toxicology
Qian Li, Zhen Dong, Weiguang Lian, Jinfeng Cui, Juan Wang, Haitao Shen, Wenjing Liu, Jie Yang, Xianghong Zhang, Hongjuan Cui
ARCHIVES OF TOXICOLOGY
(2019)
Review
Biochemistry & Molecular Biology
Zhen Dong, Muhammad Nadeem Abbas, Saima Kausar, Jie Yang, Lin Li, Li Tan, Hongjuan Cui
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2019)
Article
Biotechnology & Applied Microbiology
Huanrong Hu, Zhen Dong, Xianxing Wang, Longchang Bai, Qian Lei, Jie Yang, Lin Li, Qian Li, Lichao Liu, Yanli Zhang, Yacong Ji, Leiyang Guo, Yaling Liu, Hongjuan Cui
ONCOTARGETS AND THERAPY
(2019)
Article
Cell Biology
Zhen Dong, Xiaoxia Zhong, Qian Lei, Fei Chen, Hongjuan Cui
CELLULAR SIGNALLING
(2019)
Article
Fisheries
Muhammad Nadeem Abbas, Hanghua Liang, Saima Kausar, Zhen Dong, Hongjuan Cui
DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
(2020)
Article
Oncology
Zhen Dong, Jie Yang, Lin Li, Li Tan, Pengfei Shi, Jiayi Zhang, Xi Zhong, Lingjun Ge, Zonghui Wu, Hongjuan Cui
INTERNATIONAL JOURNAL OF ONCOLOGY
(2020)
Article
Cell Biology
Jie Yang, Zhen Dong, Aishu Ren, Gang Fu, Kui Zhang, Changhong Li, Xiangwei Wang, Hongjuan Cui
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2020)
Article
Virology
Renjian Hu, Zhen Dong, Kui Zhang, Guangzhao Pan, Chongyang Li, Hongjuan Cui
Review
Oncology
Zhen Dong, Hongjuan Cui
Article
Biochemistry & Molecular Biology
Feng Wang, Jiayi Zhang, Houyi Tang, Yi Pang, Xiaoxue Ke, Wen Peng, Shitong Chen, Muhammad Nadeem Abbas, Zhen Dong, Zhaobo Cui, Hongjuan Cui
Summary: The overexpression of CARM1 in gastric cancer correlates with poor prognosis. CARM1 interacts with Nup54 to promote its nuclear importation and cooperates with TFEB to activate Notch2 transcription, affecting gastric cancer cell proliferation and tumor formation. Methylation of N2ICD by CARM1 enhances its binding with MAML1, contributing to gastric cancer progression.
Correction
Biotechnology & Applied Microbiology
H. Hu, Z. Dong, X. Wang
ONCOTARGETS AND THERAPY
(2021)
Article
Plant Sciences
Leiyang Guo, Zhen Dong, Xiaolin Zhang, Yuanmiao Yang, Xiaosong Hu, Yacong Ji, Chongyang Li, Sicheng Wan, Jie Xu, Chaolong Liu, Yanli Zhang, Lichao Liu, Yaqiong Shi, Zonghui Wu, Yaling Liu, Hongjuan Cui
Summary: In this study, the researchers investigated the anti-tumor effect of a flavonoid called morusinol on melanoma cells. They found that morusinol could inhibit cell proliferation, induce cell cycle arrest and apoptosis, and cause DNA damage in melanoma cells. Furthermore, they discovered that morusinol could degrade CHK1 protein through the ubiquitin-proteasome pathway, leading to cell cycle arrest, apoptosis, and DNA damage response. These findings suggest that morusinol has the potential to be a candidate drug for the treatment of melanoma.
Review
Biochemistry & Molecular Biology
Liqun Yang, Pengfei Shi, Gaichao Zhao, Jie Xu, Wen Peng, Jiayi Zhang, Guanghui Zhang, Xiaowen Wang, Zhen Dong, Fei Chen, Hongjuan Cui
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2020)