Article
Chemistry, Medicinal
Ming Guo, Hao Wang, Jing Yang, Xinyu Wang, Jiahao Zhang, Shuyu Liu, Shangfei Wei, Nan Jiang, Xin Zhai
Summary: A series of novel 2,4-diarylaminopyrimidine analogues, with compound I-24 being the most promising, were developed as potent ALK inhibitors. I-24 exhibited significant anti-proliferative activity, inducing cell apoptosis and inhibiting tumor growth.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Ming Guo, Daiying Zuo, Tianming Zhao, Xiangyu Li, Jianshuang Cao, Yuxuan Qiu, Shangfei Wei, Xin Zhai
Summary: This study developed a promising ALK/ROS1 dual inhibitor to overcome ceritinib-resistant G1202R mutant, which exhibited significant cytotoxicity on multiple cell lines and showed higher anti-tumor activity compared to ceritinib.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Xinyue Wang, Yiran Hu, Xinyu Zou, Pengfei Wang, Hao Yue, Mingzhang Guo, Zefei Li, Ping Gong
Summary: Novel compounds bearing dithiocarbamate moiety were designed, synthesized, and evaluated for their inhibitory effects on drug resistance caused by ALK kinase mutations. Among them, B10 showed potent activity in inhibiting cell proliferation, enzymatic activity, inducing apoptosis, and cell cycle arrest. It is a promising candidate for treating ALKG1202R mutation.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Shuyu Liu, Fuyi Wang, Juanjuan Yang, Guangyue Su, Zhi Cao, Mengya Shan, Xin Zhai
Summary: Based on the cocrystal structure of ceritinib with anaplastic lymphoma kinase (ALK)WT protein, a series of novel 2,4-diarylaminopyrimidine analogs (L1-L25) bearing a typical piperidinyl-4-ol moiety were synthesized. Most compounds demonstrated moderate to excellent antitumor effects on ALK-positive Karpas299 and H2228 cells, with L6 showing the most optimal inhibitory activity against ALK-dependent cell lines and ALK-resistant mutations. L6 also repressed colony formation and migration of H2228 cells in a dose-dependent manner and exhibited better proapoptotic effects compared to ceritinib. The binding patterns of L6 to ALKWT and ALKG1202R were established, confirming the structural basis.
ARCHIV DER PHARMAZIE
(2023)
Article
Chemistry, Medicinal
Tao Pan, Yanrong Dan, Dafeng Guo, Junhao Jiang, Dongzhi Ran, Lin Zhang, Binghua Tian, Jianyong Yuan, Yu Yu, Zongjie Gan
Summary: The newly designed compound 10f showed potent inhibitory activity against both ALK and HDAC, effective against resistant mutants and exhibiting significant anti-proliferative effects on cancer cells at low concentrations.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Oncology
Brion W. Murray, Dayong Zhai, Wei Deng, Xin Zhang, Jane Ung, Vivian Nguyen, Han Zhang, Maria Barrera, Ana Parra, Jessica Cowell, Dong J. Lee, Herve Aloysius, Evan Rogers
Summary: TPX-0131 is a compact macrocyclic molecule designed to inhibit ALK fusion proteins, showing higher potency against a spectrum of acquired resistance mutations, especially the G1202R solvent front mutation and compound mutations, compared to current approved ALK inhibitors.
MOLECULAR CANCER THERAPEUTICS
(2021)
Article
Biochemistry & Molecular Biology
Zheng Li, Ming Guo, Meng Cao, Tianming Zhao, Mingzhu Li, Xin Zhai
Summary: A series of novel 2,4-diarylaminopyrimidine (DAAP) analogues with a 1H-benzo[d]imidazol motif were designed to address drug resistance caused by ALK kinase mutations. The most promising derivative, H-11, showed high antiproliferative and enzymatic inhibitory activities against ALK-positive cells, with established binding modes with ALK wild-type and mutants.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Oncology
Thomas McFall, Michael Trogdon, Anita C. Guizar, John F. Langenheim, Laura Sisk-Hackworth, Edward C. Stites
Summary: The combination of KRAS G12C inhibitors with EGFR inhibitors has shown consistent benefits, including inhibiting both wild-type and mutant RAS.
NPJ PRECISION ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Shariq M. Zaman, Marjorie A. Jones
Summary: In this study, the inhibitory effect of a specific alkylphenol natural product, anaephene B, and its synthesized derivatives on the protozoan parasite Leishmania tarentolae was tested. Interestingly, these compounds showed similar potency against Leishmania as they do against drug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA). Furthermore, all compounds tested in this study were able to completely inhibit L. tarentolae in vitro. This study enhances our understanding of the structure-activity relationship (SAR) between anaephene B and its analogues for potential pharmaceuticals against Leishmania infections.
Article
Chemistry, Medicinal
Ru Wang, Ting-Ting Du, Wen-Qiang Liu, Yi-Chen Liu, Ya-Dong Yang, Jin-Ping Hu, Ming Ji, Bei-Bei Yang, Li Li, Xiao-Guang Chen
Summary: By designing and testing the inhibitory effects of compounds on the STAT3 pathway, researchers have successfully developed a novel selective STAT3 inhibitor that can inhibit STAT3 phosphorylation, translocation, and downstream gene transcription. This compound has demonstrated anti-proliferative and apoptotic effects on STAT3-overactivated cancer cells and exhibited promising anti-tumor efficacy in a mouse model.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Baijiao An, Yangyang Fan, Wei Li, Wenyan Nie, Haoran Nie, Mengxuan Wang, Jie Feng, Han Yao, Yin Zhang, Xingshu Li, Geng Tian
Summary: There are currently no effective therapies for non-small cell lung cancer patients with dual mutations in EGFR and ALK, highlighting the urgent need for novel dual-target inhibitors. In this study, a series of highly effective small molecule dual inhibitors of ALK and EGFR were designed, which effectively inhibited both targets in enzymatic and cellular assays. Compound (+)-8l was shown to inhibit the phosphorylation of EGFR and ALK, induce apoptosis and cell cycle arrest, and suppress tumor growth in mouse models.
BIOORGANIC CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Artem Shvartsbart, Jeremy J. Roach, Michael R. Witten, Holly Koblish, Jennifer J. Harris, Maryanne Covington, Rodrigo Hess, Luping Lin, Michelle Frascella, Lisa Truong, Lynn Leffet, Patricia Conlen, Elham Beshad, Ron Klabe, Kamna Katiyar, Laura Kaldon, Ruth Young-Sciame, Xin He, Susan Petusky, Kwang-Jong Chen, April Horsey, Hsiang-Ting Lei, Leslie B. Epling, Marc C. Deller, Oleg Vechorkin, Wenqing Yao
Summary: This study discovered and optimized novel FGFR2/3 inhibitors that effectively inhibit common gatekeeper mutants with good selectivity over FGFR1. Through structure-activity relationship analysis, structure-based drug design, and medicinal chemistry, a potent and selective FGFR2/3 inhibitor with excellent pharmacokinetics was obtained.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Genetics & Heredity
Ziyi Yin, Jisen Shi, Yan Zhen
Summary: Through TMT quantitative phosphoproteomics analysis, this study investigated the impact of CIPK3/9/23/26 quadruple mutant on magnesium sensitivity in Arabidopsis, identifying significant changes in multiple phosphorylation modification sites. Further bioinformatics analysis revealed potential pathways associated with magnesium sensitivity.
Article
Chemistry, Physical
Michael Kotik, Katerina Brodsky, Petr Halada, Hana Javurkova, Helena Pelantova, Dorota Konvalinkova, Pavla Bojarova, Vladimir Kren
Summary: Two newly identified wild-type rutinosidases from glycoside hydrolase family 5-23 can glycosylate inorganic azide with rutin as a donor, producing rutinosyl alpha-azide. The catalytic nucleophile mutant of rutinosidase from Aspergillus niger, also belonging to GH5-23, was able to synthesize rutinosyl beta-azide. Thus, both anomers of rutinosyl azide can be synthesized at a preparatory scale using either wild-type or mutant rutinosidases of GH5-23.
CATALYSIS COMMUNICATIONS
(2021)
Article
Chemistry, Medicinal
Katsuki Takashima, Miyu Teramachi, Shinsuke Marumoto, Fumihiro Ishikawa, Yoshiaki Manse, Toshio Morikawa, Genzoh Tanabe
Summary: The alkaloid 4,5-didehydroguadiscine (12a) with potent melanogenesis-inhibitory activity has been isolated from Hornschuchia obliqua. This study investigates the structure-activity relationship of 12a by preparing five analogs (12b-12f) and five benzylisoquinoline analogs (13b-13f). The results suggest that the C11a-C11b bond plays an essential role in the melanogenesis-inhibitory activities of 12a-12e.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Biochemistry & Molecular Biology
Syed R. Ali, Zhiqing Liu, Miroslav N. Nenov, Oluwarotimi Folorunso, Aditya Singh, Federico Scala, Haiying Chen, T. F. James, Musaad Alshammari, Neli I. Panova-Elektronova, Mark Andrew White, Jia Zhou, Fernanda Laezza
ACS CHEMICAL NEUROSCIENCE
(2018)
Article
Chemistry, Medicinal
Zhiqing Liu, Bing Tian, Haiying Chen, Pingyuan Wang, Allan R. Brasier, Jia Zhou
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2018)
Article
Biochemistry & Molecular Biology
Bing Tian, Zhiqing Liu, Julia Litvinov, Rosario Maroto, Mohammad Jamaluddin, Erik Rytting, Igor Patrikeev, Lorenzo Ochoa, Gracie Vargas, Massoud Motamedi, Bill T. Ameredes, Jia Zhou, Allan R. Brasier
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2019)
Article
Chemistry, Medicinal
Zhiqing Liu, Paul Wadsworth, Aditya K. Singh, Haiying Chen, Pingyuan Wang, Oluwarotimi Folorunso, Pietro Scaduto, Syed R. Ali, Fernanda Laezza, Jia Zhou
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2019)
Article
Allergy
Bing Tian, Koa Hosoki, Zhiqing Liu, Jun Yang, Yingxin Zhao, Hong Sun, Jia Zhou, Erik Rytting, Lata Kaphalia, William J. Calhoun, Sanjiv Sur, Allan R. Brasier
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2019)
Article
Medicine, Research & Experimental
Qingli Niu, Zhiqing Liu, Edrous Alamer, Xiuzhen Fan, Haiying Chen, Janice Endsley, Benjamin B. Gelman, Bing Tian, Jerome H. Kim, Nelson L. Michael, Merlin L. Robb, Jintanat Ananworanich, Jia Zhou, Haitao Hu
JOURNAL OF CLINICAL INVESTIGATION
(2019)
Article
Biochemical Research Methods
Yingxin Zhao, Bing Tian, Hong Sun, Jing Zhang, Yueqing Zhang, Maxim Ivannikov, Massoud Motamedi, Zhiqing Liu, Jia Zhou, Lata Kaphalia, William J. Calhoun, Rosario Maroto, Allan R. Brasier
JOURNAL OF PROTEOMICS
(2019)
Article
Chemistry, Medicinal
Zhiqing Liu, Haiying Chen, Pingyuan Wang, Yi Li, Eric A. Wold, Paul G. Leonard, Sarah Joseph, Allan R. Brasier, Bing Tian, Jia Zhou
JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Article
Chemistry, Medicinal
Pingyuan Wang, Urszula Luchowska-Stanska, Boy van Basten, Haiying Chen, Zhiqing Liu, Jolanta Wiejak, Padraic Whelan, David Morgan, Emma Lochhead, Graeme Barker, Holger Rehmann, Stephen J. Yarwood, Jia Zhou
JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Article
Virology
Edrous Alamer, Chaojie Zhong, Zhiqing Liu, Qingli Niu, Fuquan Long, Lulu Guo, Benjamin B. Gelman, Lynn Soong, Jia Zhou, Haitao Hu
JOURNAL OF VIROLOGY
(2020)
Article
Pharmacology & Pharmacy
Zijun Zhou, Xiaoming Li, Zhiqing Liu, Lixun Huang, Yuying Yao, Liuyou Li, Jian Chen, Rongxin Zhang, Jia Zhou, Lijing Wang, Qian-Qian Zhang
FRONTIERS IN PHARMACOLOGY
(2020)
Article
Chemistry, Medicinal
Pingyuan Wang, Dharini van der Hoeven, Na Ye, Haiying Chen, Zhiqing Liu, Xiaoping Ma, Dina Montufar-Solis, Kristen M. Rehl, Kwang-Jin Cho, Sabita Thapa, Wei Chen, Ransome van der Hoeven, Jeffrey A. Frost, John F. Hancock, Jia Zhou
Summary: KRAS plays a crucial role in cell proliferation, differentiation, migration, and survival, with mutated KRAS being a major driver of multiple human cancers. Several new compounds were discovered in the study as more effective KRAS plasma membrane localization inhibitors, showing potential as chemical probes and anticancer therapeutics.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Zhiqing Liu, Pingyuan Wang, Eric A. Wold, Qiaoling Song, Chenyang Zhao, Changyun Wang, Jia Zhou
Summary: Researchers have made significant progress in the discovery and development of small-molecule inhibitors targeting the canonical WNT pathway in recent years, with a focus on specific target proteins and candidates in clinical trials. The study also highlights the challenges and opportunities in effectively targeting this pathway while maintaining a balance between efficacy and toxicity.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Gastroenterology & Hepatology
Yi Li, Jianping Chen, Andrew A. Bolinger, Haiying Chen, Zhiqing Liu, Yingzi Cong, Allan R. Brasier, Irina Pinchuk, Bing Tian, Jia Zhou
Summary: Inflammatory bowel disease (IBD) is a serious chronic gastrointestinal disease, with long-term inflammation contributing to neoplastic transformation and colorectal cancer development. The discovery of new small molecule drugs targeting specific pathways in mucosal inflammation offers hope for the treatment of IBD.
INFLAMMATORY BOWEL DISEASES
(2021)
Article
Chemistry, Medicinal
Zhiqing Liu, Yi Li, Haiying Chen, Hsien-Tsung Lai, Pingyuan Wang, Shwu-Yuan Wu, Eric A. Wold, Paul G. Leonard, Sarah Joseph, Haitao Hu, Cheng-Ming Chiang, Allan R. Brasier, Bing Tian, Jia Zhou
Summary: A potent BRD4 BD1-selective inhibitor ZL0590 has been discovered, targeting a unique binding site and exhibiting significant anti-inflammatory activities. This finding provides new insights into the complex biology of bromodomain specificity among BRD4 and its protein-protein interaction partners.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)