Article
Biochemistry & Molecular Biology
Xinran Wang, Cai Zhang, Xiangyu Zhang, Jiming Wang, Liyu Zhao, Dongmei Zhao, Maosheng Cheng
Summary: In this study, a series of 2-aminopyrimidine derivatives were designed and synthesized as LSD1 inhibitors based on the AZD9291 skeleton. The most promising compound, X43, showed remarkable LSD1 selectivity and inhibitory activity against cell proliferation. It also induced apoptosis in A549 cells.
BIOORGANIC CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Xuemei Li, Peipei Wang, Chang Wang, Tingting Jin, Ran Xu, Lexian Tong, Xiaobei Hu, Liteng Shen, Jia Li, Yubo Zhou, Tao Liu
Summary: FLT3 inhibitors as single agents have limited effects due to acquired and adaptive resistance, as well as cardiotoxicity related to hERG channel blockade. A dual FLT3/CHK1 inhibitor 18 was found to overcome acquired resistance and reduce hERG affinity in BaF3 cells with FLT3-TKD and FLT3-ITD-TKD mutations. It demonstrated high selectivity over c-KIT and had favorable PK profiles and safety in in vivo studies, making it a promising candidate for further development.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Xuanmin Lian, Yue Gao, Xuemei Li, Peipei Wang, Lexian Tong, Jia Li, Yubo Zhou, Tao Liu
Summary: This study describes the design, synthesis, and biological evaluation of a series of 2-aminopyrimidine derivatives as potent FLT3 inhibitors. Compound 15 shows promising potential for the treatment of AML.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Chemistry, Medicinal
Wuqing Deng, Xiaojuan Chen, Kaili Jiang, Xiaojuan Song, Minhao Huang, Zheng-Chao Tu, Zhang Zhang, Xiaojing Lin, Raquel Ortega, Adam Patterson, Jeff B. Smaill, Ke Ding, Suming Chen, Yongheng Chen, Xiaoyun Lu
Summary: Covalent kinase inhibitors, particularly those with chemically tuned warheads such as α-fluoro acrylamide, vinylsulfonamide, and acetaldehyde amine, have shown selective inhibition of FGFR4 with compounds 6h and 6i providing structural information for the rational design of new selective FGFR4 inhibitors.
ACS MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Biochemistry & Molecular Biology
ShaSha Wang, Yidan Huo, Jinmiao Zhang, Longfei Li, Fei Cao, Yali Song, Yajing Zhang, Kan Yang
Summary: Targeting sphingosine kinase 2 (SphK2) has been identified as a novel strategy for cancer treatment. However, there is a lack of potent and selective SphK2 inhibitors. In this study, a series of novel SphK2 inhibitors were designed, synthesized, and screened, with compound 12e showing the strongest inhibitory activity. Molecular dynamics simulations were performed to analyze the detailed interactions between SphK2 and its inhibitors. In addition, 12e exhibited anti-proliferative activity in various cancer cells and inhibited the migration of MCF-7 breast cancer cells.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Shidi Xu, Zhihui Zhou, Jie He, Jiaojiao Guo, Xiaoling Huang, Yufeng An, Qingshan Pan, Shan Xu, Wufu Zhu
Summary: In this study, several series of compounds were designed and synthesized based on the binding model between Angew2017-7634-1 and EGFR(T790M/C797S), and their bioactivities were evaluated. Compound A23 was found to effectively inhibit the proliferation of tumor cells and promote their death, making it a potential inhibitor for the treatment of non-small-cell lung cancer.
ARCHIV DER PHARMAZIE
(2023)
Article
Chemistry, Medicinal
Samar El-Kalyoubi, Samiha A. El-Sebaey, Sherin M. Elfeky, Hanan A. AL-Ghulikah, Mona S. El-Zoghbi
Summary: In this study, a combination of structural-based drug design and solvent-free synthesis led to the discovery of several novel compounds with excellent anticancer activity. These compounds showed significant inhibition against BRD4 and PLK1, triggered apoptosis, and halted cell growth. Furthermore, they exhibited ideal drug-like properties and pharmacokinetics, making them promising candidates for anticancer drugs.
Article
Chemistry, Medicinal
Yingxue Li, Yaoyao Chang, Jianfang Fu, Rongcai Ding, Lingyun Zhang, Tian Liang, Yajing Liu, Yue Liu, Jinxing Hu
Summary: The compound A12 designed and synthesized based on the principle of collocation as an EGFR(L858R/T790M) kinase inhibitor showed excellent anti-tumor activity and selectivity, indicating great potential for research and drug development.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Yizhu Xu, Huanhuan Wu, Lei Huang, Bingxin Zhai, Xiaofei Li, Shuaiqi Xu, Xingxin Wu, Qihua Zhu, Qiang Xu
Summary: Targeting both PARP-1 and TNKS1/2 with dual inhibitors provides a promising strategy for expanding the clinical application of PARP-1 inhibitors and overcoming resistance. Compound I-9, a dual PARP-1/2 and TNKS1/2 inhibitor, exhibits excellent antitumor efficacy and shows potential as a novel agent for cancer therapy.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Samir Mohamed Rayes, Gaber El-Enany, Mohamed Sayed Gomaa, Ibrahim A. I. Ali, Walid Fathalla, Faheem Hyder Pottoo, Firdos Alam Khan
Summary: A series of new quinoxaline derivatives were synthesized and their effects on cancer cell viability and proliferation were studied. Thirteen compounds showed inhibitory activity against HCT-116 cancer cells, while fifteen compounds showed activity against MCF-7 cancer cells. Molecular modeling studies indicated that these compounds can selectively inhibit the enzyme by stabilizing its inactive conformation.
Article
Biochemistry & Molecular Biology
Yujeong Lee, Yoshiyuki Onishi, Lisa McPherson, Anna M. Kietrys, Marian Hebenbrock, Yong Woong Jun, Ishani Das, Shanthi Adimoolam, Debin Ji, Michael G. Mohsen, James M. Ford, Eric T. Kool
Summary: Impaired DNA repair activity is associated with increased cancer rates. This study found that certain tyrosine kinase inhibitors, such as nilotinib, can activate the repair enzyme MTH1, which cleanses oxidatively damaged nucleotides. Structural optimization resulted in compounds that strongly activate MTH1 and decrease mutagenic nucleotides in cellular DNA. These findings suggest that MTH1 activators may be a promising strategy to suppress tumorigenesis in individuals with elevated cancer risks.
ACS CHEMICAL BIOLOGY
(2022)
Article
Chemistry, Medicinal
Xi Xu, Di Zhang, Tengteng Zhao, Min Wang, Yu Li, Qianming Du, Junping Kou, Zhiyu Li, Jinlei Bian
Summary: A series of novel biphenyl-based scaffold derivatives were identified as selective HDAC6 inhibitors, exhibiting good inhibitory activity and selectivity. Compound C10, in particular, showed potent HDAC inhibition, anti-proliferative and anti-migration effects on cancer cells, and significant antitumor efficacy in a mouse colon cancer model.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Hangcheng Ni, Yu Li, Jieyi Deng, Xingzi Shi, Qinhai Pan
Summary: By using aldehydes as radical precursors under visible-light irradiation, a mild and simple C-H acylation reaction of quinoxalin-2(1H)-ones was achieved, allowing for the incorporation of various functional groups. The method was not only applicable for the synthesis of compounds, but also for the modification of natural molecules and pharmaceutically relevant compounds.
NEW JOURNAL OF CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Sarosh Iqbal, Nimra Naveed Shaikh, Khalid Mohammed Khan, Shumaila Kiran, Sehrish Naz, Zaheer Ul-Haq, Shahnaz Perveen, M. Iqbal Choudhary
Summary: This study successfully synthesized 27 2-aminopyrimidine derivatives and evaluated their beta-glucuronidase inhibitory activity. Among them, compound 24 showed significantly higher activity than the standard compound. In addition, in silico study predicted the binding mode of the substrate and enzyme.
Article
Chemistry, Medicinal
Yawen Yang, Qingqing Liu, Xinyi Wang, Shaohua Gou
Summary: A series of novel histone deacetylase (HDAC) inhibitors derived from 3-(benzazol-2-yl)quinoxaline derivatives were designed and synthesized using a pharmacophore fusion strategy. In vitro studies demonstrated that most of the synthesized compounds exhibited significant anti-proliferative activity. Among them, compound 10c showed the highest cytotoxicity in HCT-116 cells with an IC50 value of 0.91 μM, surpassing Vorinostat (5.66 μM). Further investigation revealed that compound 10c up-regulated the acetylation levels of H3 and alpha-tubulin, inhibited Topo I, and induced the release of apoptotic biomarkers, highlighting its potential as a promising anti-cancer HDAC inhibitor.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Chemistry, Medicinal
Wylie S. Palmer, Guillaume Poncet-Montange, Gang Liu, Alessia Petrocchi, Naphtali Reyna, Govindan Subramanian, Jay Theroff, Anne Yau, Maria Kost-Alimova, Jennifer P. Bardenhagen, Elisabetta Leo, Hannah E. Shepard, Trang N. Tieu, Xi Shi, Yanai Zhao, Shuping Zhao, Michelle C. Barton, Giulio Draetta, Carlo Toniatti, Philip Jones, Mary Geck Do, Jannik N. Andersen
JOURNAL OF MEDICINAL CHEMISTRY
(2016)
Article
Biochemistry & Molecular Biology
Celine Kerros, Satyendra C. Tripathi, Dongxing Zha, Jennifer M. Mehrens, Anna Sergeeva, Anne V. Philips, Na Qiao, Haley L. Peters, Hiroyuki Katayama, Pariya Sukhumalchandra, Kathryn E. Ruisaard, Alexander A. Perakis, Lisa S. St. John, Sijie Lu, Elizabeth A. Mittendorf, Karen Clise-Dwyer, Amanda C. Herrmann, Gheath Alatrash, Carlo Toniatti, Samir M. Hanash, Qing Ma, Jeffrey J. Molldrem
JOURNAL OF BIOLOGICAL CHEMISTRY
(2017)
Article
Multidisciplinary Sciences
Giannicola Genovese, Alessandro Carugo, James Tepper, Frederick Scott Robinson, Liren Li, Maria Svelto, Luigi Nezi, Denise Corti, Rosalba Minelli, Piergiorgio Pettazzoni, Tony Gutschner, Chia-Chin Wu, Sahil Seth, Kadir Caner Akdemir, Elisabetta Leo, Samirkumar Amin, Marco Dal Molin, Haoqiang Ying, Lawrence N. Kwong, Simona Colla, Koichi Takahashi, Papia Ghosh, Virginia Giuliani, Florian Muller, Prasenjit Dey, Shan Jiang, Jill Garvey, Chang-Gong Liu, Jianhua Zhang, Timothy P. Heffernan, Carlo Toniatti, Jason B. Fleming, Michael G. Goggins, Laura D. Wood, Alessandro Sgambato, Abbas Agaimy, Anirban Maitra, Charles W. M. Roberts, Huamin Wang, Andrea Viale, Ronald A. DePinho, Giulio F. Draetta, Lynda Chin
Article
Biochemistry & Molecular Biology
Likun Li, Styliani Karanika, Guang Yang, Jiangxiang Wang, Sanghee Park, Bradley M. Broom, Ganiraju C. Manyam, Wenhui Wu, Yong Luo, Spyridon Basourakos, Jian H. Song, Gary E. Gallick, Theodoros Karantanos, Dimitrios Korentzelos, Abul Kalam Azad, Jeri Kim, Paul G. Corn, Ana M. Aparicio, Christopher J. Logothetis, Particia Troncoso, Timothy Heffernan, Carlo Toniatti, Hyun-Sung Lee, Ju-Seog Lee, Xuemei Zuo, Wenjun Chang, Jianhua Yin, Timothy C. Thompson
Article
Biochemistry & Molecular Biology
Likun Li, Styliani Karanika, Guang Yang, Jiangxiang Wang, Sanghee Park, Bradley M. Broom, Ganiraju C. Manyam, Wenhui Wu, Yong Luo, Spyridon Basourakos, Jian H. Song, Gary E. Gallick, Theodoros Karantanos, Dimitrios Korentzelos, Abul Kalam Azad, Jeri Kim, Paul G. Corn, Ana M. Aparicio, Christopher J. Logothetis, Particia Troncoso, Timothy Heffernan, Carlo Toniatti, Hyun-Sung Lee, Ju-Seog Lee, Xuemei Zuo, Wenjun Chang, Jianhua Yin, Timothy C. Thompson
Article
Biochemistry & Molecular Biology
Jennifer R. Molina, Yuting Sun, Marina Protopopova, Sonal Gera, Madhavi Bandi, Christopher Bristow, Timothy McAfoos, Pietro Morlacchi, Jeffrey Ackroyd, Ahmed-Noor A. Agip, Gheath Al-Atrash, John Asara, Jennifer Bardenhagen, Caroline C. Carrillo, Christopher Carroll, Edward Chang, Stefan Ciurea, Jason B. Cross, Barbara Czako, Angela Deem, Naval Daver, John Frederick de Groot, Jian-Wen Dong, Ningping Feng, Guang Gao, Jason Gay, Mary Geck Do, Jennifer Greer, Virginia Giuliani, Jing Han, Lina Han, Verlene K. Henry, Judy Hirst, Sha Huang, Yongying Jiang, Zhijun Kang, Tin Khor, Sergej Konoplev, Yu-Hsi Lin, Gang Liu, Alessia Lodi, Timothy Lofton, Helen Ma, Mikhila Mahendra, Polina Matre, Robert Mullinax, Michael Peoples, Alessia Petrocchi, Jaime Rodriguez-Canale, Riccardo Serreli, Thomas Shi, Melinda Smith, Yoko Tabe, Jay Theroff, Stefano Tiziani, Quanyun Xu, Qi Zhang, Florian Muller, Ronald A. DePinho, Carlo Toniatti, Giulio F. Draetta, Timothy P. Heffernan, Marina Konopleva, Philip Jones, M. Emilia Di Francesco, Joseph R. Marszalek
Article
Cell Biology
Yuting Sun, Madhavi Bandi, Timothy Lofton, Melinda Smith, Christopher A. Bristow, Alessandro Carugo, Norma Rogers, Paul Leonard, Qing Chang, Robert Mullinax, Jing Han, Xi Shi, Sahil Seth, Brooke A. Meyers, Meredith Miller, Lili Miao, Xiaoyan Ma, Ningping Feng, Virginia Giuliani, Mary Geck Do, Barbara Czako, Wylie S. Palmer, Faika Mseeh, John M. Asara, Yongying Jiang, Pietro Morlacchi, Shuping Zhao, Michael Peoples, Trang N. Tieu, Marc O. Warmoes, Philip L. Lorenzi, Florian L. Muller, Ronald A. DePinho, Giulio F. Draetta, Carlo Toniatti, Philip Jones, Timothy P. Heffernan, Joseph R. Marszalek
Article
Multidisciplinary Sciences
Beatrice Biferali, Valeria Bianconi, Daniel Fernandez Perez, Sophie Poehle Kronawitter, Fabrizia Marullo, Roberta Maggio, Tiziana Santini, Federica Polverino, Stefano Biagioni, Vincenzo Summa, Carlo Toniatti, Diego Pasini, Sigmar Stricker, Romano Di Fabio, Fulvio Chiacchiera, Giovanna Peruzzi, Chiara Mozzetta
Summary: The study identified Prdm16 as a nuclear envelope protein that anchors H3K9-methylated chromatin in a cell-specific manner and regulates developmental capacities of fibro-adipogenic progenitors (FAPs). Prdm16 orchestrates lamina-associated domain organization and heterochromatin sequestration at the nuclear periphery, affecting gene expression and cell fate in FAPs.
Article
Biochemistry & Molecular Biology
Stefania Colarusso, Federica Ferrigno, Simona Ponzi, Francesca Pavone, Immacolata Conte, Luigi Abate, Elisa Beghetto, Antonino Missineo, Jerome Amaudrut, Alberto Bresciani, Giacomo Paonessa, Licia Tomei, Christian Montalbetti, Elisabetta Bianchi, Carlo Toniatti, Jesus M. M. Ontoria
Summary: By conducting a structure-activity relationship (SAR) study, researchers have discovered compounds with high selectivity and potential anti-Zika virus activity.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Biology
Giacomo Paonessa, Giulia Siciliano, Rita Graziani, Cristiana Lalli, Ottavia Cecchetti, Cristina Alli, Roberto La Valle, Alessia Petrocchi, Alessio Sferrazza, Monica Bisbocci, Mario Falchi, Carlo Toniatti, Alberto Bresciani, Pietro Alano
Summary: High-throughput screening and validation assays have identified potential antimalarial drugs that can kill both sexual and asexual blood stages of Plasmodium falciparum, thus blocking parasite transmission through mosquitoes.
COMMUNICATIONS BIOLOGY
(2022)
Article
Medicine, Research & Experimental
Guglielmo Sorci, Davide Gabellini
EUROPEAN JOURNAL OF TRANSLATIONAL MYOLOGY
(2020)
Article
Chemistry, Medicinal
Michael J. Soth, Kang Le, Maria Emilia Di Francesco, Matthew M. Hamilton, Gang Liu, Jason P. Burke, Chris L. Carroll, Jeffrey J. Kovacs, Jennifer P. Bardenhagen, Christopher A. Bristow, Mario Cardozo, Barbara Czako, Elisa de Stanchina, Ningping Feng, Jill R. Garvey, Jason P. Gay, Mary K. Geck Do, Jennifer Greer, Michelle Han, Angela Harris, Zachary Herrera, Sha Huang, Virginia Giuliani, Yongying Jiang, Sarah B. Johnson, Troy A. Johnson, Zhijun Kang, Paul G. Leonard, Zhen Liu, Timothy McAfoos, Meredith Miller, Pietro Morlacchi, Robert A. Mullinax, Wylie S. Palmer, Jihai Pang, Norma Rogers, Charles M. Rudin, Hannah E. Shepard, Nakia D. Spencer, Jay Theroff, Qi Wu, Alan Xu, Ju Anne Yau, Giulio Draetta, Carlo Toniatti, Timothy P. Heffernan, Philip Jones
JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Article
Oncology
Hong Jiang, Yisel Rivera-Molina, Candelaria Gomez-Manzano, Karen Clise-Dwyer, Laura Bover, Luis M. Vence, Ying Yuan, Frederick F. Lang, Carlo Toniatti, Mohammad B. Hossain, Juan Fueyo
Article
Chemistry, Medicinal
Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan
Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang
Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman
Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li
Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang
Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla
Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
