Article
Biochemistry & Molecular Biology
Ru Dong, Cheng Zhang, Chao Wang, Xin Zhou, Wen Li, Jin-Yang Zhang, Min Wang, Yong Xu, Li-Ping Sun
Summary: This study designed a new series of 3-methyl-1H-indazole derivatives targeting the inhibitory activities of protein BRD4-BD1 and cancer cell proliferation. Compound 9d showed excellent selectivity for BRD4 and effectively suppressed c-Myc. The study provided new lead compounds for further evaluation on BRD4.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Michael Bauder, Christian Meyners, Patrick L. Purder, Stephanie Merz, Wisely Oki Sugiarto, Andreas M. Voll, Tim Heymann, Felix Hausch
Summary: The design and synthesis of macrocyclic FKBP51-selective ligands with high affinity and selectivity through incorporation of polar functionalities demonstrates a viable strategy to target the shallow FKBP51 binding site selectively. The high-resolution crystal structures of six macrocyclic inhibitors in complex with FKBP51 confirmed the desired selectivity-enabling binding mode, highlighting the potential of macrocyclization as an effective approach in drug development.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Chengqian Wei, Junjie Huang, Yu Wang, Yifang Chen, Xin Luo, Shaobo Wang, Zengxue Wu, Jixiang Chen
Summary: A series of new oxadiazole sulfone derivatives containing an amide moiety were synthesized to screen high-efficiency antibacterial agents for rice bacterial diseases. Compound 10 showed excellent antibacterial activity against Xanthomonas oryzae pv. oryzae and Xanthomonas oryzae pv. oryzicola, with EC50 values superior to commercial bactericides. Compound 10 demonstrated superior protective and curative activities against rice bacterial leaf blight and rice bacterial leaf streak compared to other tested compounds. Additionally, compound 10 exhibited potential mechanisms of action by affecting extracellular polysaccharides, cell membranes, and enzyme activity of dihydrolipoamide S-succinyltransferase to inhibit the growth of Xanthomonas oryzae pv. oryzae and Xanthomonas oryzae pv. oryzicola.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Keliang Wu, Chenghua Zhang, Bing He, Huanxin Li, Shan Tang, Tao Han, Bingke Li
Summary: The machine learning models established for BRD4 inhibitors showed good predictive performance and identified potential compounds through virtual screening. The molecules selected from the hits demonstrated strong interaction with BRD4 in docking calculations and exhibited binding stability in molecular dynamics simulations.
Article
Medicine, Research & Experimental
Seoyeon Jeong, Hwa-Ryeon Kim, June-Ha Shin, Min-Hee Son, In-Hyun Lee, Jae-Seok Roe
Summary: Researchers used DNA-encoded library screening to identify BBC1115 as a selective BET inhibitor that suppresses aberrant cell fate programs. BBC1115 impaired proliferation in various cancer cells and inhibited tumor growth with minimal toxicity in vivo. This study demonstrates that integrating DEL screening and biological validation is a reliable strategy for discovering new compounds targeting proteins involved in epigenetic regulation in human malignancies.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2023)
Article
Biochemistry & Molecular Biology
Tengyue Zhang, Siqi Xing, Jiyu Du, Jucheng Xia, Shuanghong Dong, Zeng Li, Zhicheng Liu, Yang Song
Summary: In this study, a receptor structure-based virtual screening strategy was developed to identify potential TLR/MD2 inhibitors for inflammatory diseases. Hit compound 94 exhibited promising anti-inflammatory activity and low toxicity, inhibiting the activation of TLR4/MD2-associated signaling pathways.
BIOORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Xue-ping Hu, Liu Yang, Xin Chai, Yi-xuan Lei, Md Shah Alam, Lu Liu, Chao Shen, De-jun Jiang, Zhe Wang, Zhi-yong Liu, Lei Xu, Kang-lin Wan, Tian-yu Zhang, Yue-lan Yin, Dan Li, Dong-sheng Cao, Ting-jun Hou
Summary: This study utilized an integrated molecular modeling strategy to identify two lead compounds that could inhibit DprE1 and showed inhibitory activity against Mycobacterium tuberculosis in vitro, with low cytotoxicity against mouse embryo fibroblast NIH-3T3 cells. This research provides an effective strategy for discovering novel anti-TB lead compounds.
ACTA PHARMACOLOGICA SINICA
(2022)
Article
Pharmacology & Pharmacy
Gaia Pasqualetto, Marika Zuanon, Andrea Brancale, Mark T. Young
Summary: The ATP-gated ion channels P2X4 and P2X7 receptors are drug targets for inflammatory pain. Through virtual screening, a compound (GP-25) was found to display antagonist activity at human P2X7 but not at human P2X4. Further screening led to the discovery of five additional compounds with antagonist activity at human P2X7. Docking experiments revealed the structural basis for the lack of activity of GP-25 at human P2X4.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Shih-Chung Yen, Liang-Chieh Chen, Han-Li Huang, Wei-Chun HuangFu, Yi-Ying Chen, Ssu-Ting Lien, Hui-Ju Tseng, Tzu-Ying Sung, Jui-Hua Hsieh, Wei-Jan Huang, Shiow-Lin Pan, Kai-Cheng Hsu, Tony Eight Lin
Summary: A dual inhibitor, K783-0308, targeting FLT3 and MNK2, was identified in this study. It showed inhibitory effects on both FLT3 and MNK2, as well as promising results in suppressing AML cell growth and inducing cell cycle arrest.
BIOORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Dongyan Gu, Mengmeng Zhang, Lvtao Cai, Chang Wang, Yu -Bo Zhou, Jia Li, Rong Sheng
Summary: Compound 1 with pyrazolo[1,5-a]quinoxalin-4(5H)-one scaffold was identified as a hit for inhibiting PI3K alpha activity through virtual screening. Structural modifications based on similarity search and molecular docking yielded a novel series of pyrazolo[1,5-a]quinoxalin-4(5H)-one derivatives. The most potent compound 49b exhibited improved PI3K alpha inhibitory activity with good isoform selectivity and demonstrated promising pharmacokinetic properties. Further development of compound 49b as a potential PI3Ka inhibitor is warranted.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Zi-Ying Zhou, Xiao-Yang Han, Lian-Qi Sun, Si-Yan Li, Si-Tu Xue, Zhuo-Rong Li
Summary: This study demonstrates the association between FOXM1 protein and drug resistance in ovarian cancer, and identifies DZY-4 as a potential inhibitor with high affinity and anti-tumor effects, making it a potential treatment option for ovarian cancer.
FRONTIERS IN CHEMISTRY
(2022)
Article
Oncology
Xiaotong Chen, Yunshuo Zhao, Sifan Lyu, Guanfei Gao, Yanfeng Gao, Yuanming Qi, Jiangfeng Du
Summary: This study identified four small molecules with novel scaffolds that can inhibit glucose uptake into cancer cells at the sub-micromole level, offering potential as anti-cancer drug candidates by manipulating energy metabolism.
INVESTIGATIONAL NEW DRUGS
(2021)
Article
Chemistry, Physical
Junmin Dong, Xinghe Wang
Summary: BRD4 is an epigenetic reader that regulates chromatin structure and gene expression by binding acetylated lysine in histones. A virtual screening approach was used to identify potential BRD4 inhibitors from the ZINC database. Molecular docking and molecular dynamics simulation revealed that ZINC16645732 might be a potential BRD4 inhibitor with better binding free energy than the positive drug PF-1, suggesting the need for further experimental analysis and modification.
JOURNAL OF MOLECULAR STRUCTURE
(2023)
Article
Biochemistry & Molecular Biology
Soumen Barman, Snehasudha Subhadarsini Sahoo, Jyotirmayee Padhan, Babu Sudhamalla
Summary: Bromodomains are structural motifs that recognize acetylated lysine residues on histone tails and play a crucial role in gene expression regulation. This study aims to identify natural compounds as inhibitors of the BRD4-BD1 bromodomain through virtual screening. Three promising natural product inhibitors were identified.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Biology
Ammar D. Elmezayen, Yelekci Kemal
Summary: The fundamental cause of human cancer is strongly influenced by epigenetic factors, with research focusing on identifying isoform-selective inhibitors against specific HDACs through structure-based drug design. The top-ranked inhibitors showed high binding affinity and isoform selectivity, making them potential drug candidates for further optimization towards designing safe isoform-selective HDAC inhibitors.
COMPUTATIONAL BIOLOGY AND CHEMISTRY
(2021)
Article
Chemistry, Physical
Sundar Raman Subramanian, Ettayapuram Ramaprasad Azhagiya Singam, Michael Berinski, Venkatesan Subramanian, Rebecca C. Wade
JOURNAL OF PHYSICAL CHEMISTRY B
(2016)
Article
Chemistry, Physical
Aafiya Tarannum, Charuvaka Muvva, Ami Mehta, J. Raghava Rao, N. Nishad Fathima
JOURNAL OF PHYSICAL CHEMISTRY B
(2016)
Article
Multidisciplinary Sciences
Charuvaka Muvva, Sanjukta Patra, Subramanian Venkatesan
Article
Chemistry, Multidisciplinary
Azhagiya Singam Ettayapuram Ramaprasad, Shahid Uddin, Jose Casas-Finet, Donald J. Jacobs
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2017)
Article
Chemistry, Multidisciplinary
M. B. Camarada, J. Comer, H. Poblete, E. R. Azhagiya Singam, V. Marquez-Miranda, C. Morales-Verdejo, F. D. Gonzalez-Nilo
Article
Chemistry, Physical
Nikita Nikulsin, E. R. Azhagiya Singam, Gloria Elliott, Donald Jacobs
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2018)
Article
Chemistry, Physical
E. R. Azhagiya Singam, Yuntao Zhang, Geraldine Magnin, Ingrid Miranda-Carvajal, Logan Coates, Ravindra Thakkar, Horacio Poblete, Jeffrey Comer
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2019)
Article
Chemistry, Multidisciplinary
K. Rasheeda, Charuvaka Muvva, Nishter Nishad Fathima
Article
Chemistry, Physical
Ettayapuram Ramaprasad Azhagiya Singam, Phum Tachachartvanich, Michele A. La Merrill, Martyn T. Smith, Kathleen A. Durkin
JOURNAL OF PHYSICAL CHEMISTRY B
(2019)
Review
Chemistry, Medicinal
Charuvaka Muvva, N. Arul Murugan, Venkata Surya Kumar Choutipalli, Venkatesan Subramanian
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2019)
Article
Biochemistry & Molecular Biology
Natarajan Arul Murugan, Charuvaka Muvva, Chitra Jeyarajpandian, Jeyaraman Jeyakanthan, Venkatesan Subramanian
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Biochemistry & Molecular Biology
Charuvaka Muvva, Natarajan Arul Murugan, Venkatesan Subramanian
Summary: The study utilized umbrella sampling simulations and electronic structure theory calculations to analyze the aggregation process of amyloid and tau protein sequences, revealing that monomers of these sequences exhibit alpha-helix like secondary structures, while dimers show double well potentials corresponding to alpha-helix and beta-sheet like secondary structures. Complementary semi-empirical and density functional theory calculations validated the force-field based free energy profiles obtained for these systems.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Anamika Singh Gaur, Anshu Bhardwaj, Arun Sharma, Lijo John, M. Ram Vivek, Neha Tripathi, Prasad V. Bharatam, Rakesh Kumar, Sridhara Janardhan, Abhaysinh Mori, Anirban Banerji, Andrew M. Lynn, Anmol J. Hemrom, Anurag Passi, Aparna Singh, Asheesh Kumar, Charuvaka Muvva, Chinmai Madhuri, Chinmayee Choudhury, D. Arun Kumar, Deepak Pandit, Deepak R. Bharti, Devesh Kumar, E. R. Azhagiya Singam, Gajendra P. S. Raghava, Hari Sailaja, Harish Jangra, Kaamini Raithatha, Karunakar Tanneeru, Kumardeep Chaudhary, M. Karthikeyan, M. Prasanthi, Nandan Kumar, N. Yedukondalu, Neeraj K. Rajput, P. Sri Saranya, Pankaj Narang, Prasun Dutta, R. Venkata Krishnan, Reetu Sharma, R. Srinithi, Ruchi Mishra, S. Hemasri, Sandeep Singh, Subramanian Venkatesan, Suresh Kumar, Uca Jaleel, Vijay Khedkar, Yogesh Joshi, G. Narahari Sastry
JOURNAL OF CHEMICAL SCIENCES
(2017)
Meeting Abstract
Biophysics
Ettayapuram Ramaprasad Azhagiya Singam, Shahid Uddin, Jose Casas-Finet, Donald J. Jacobs
BIOPHYSICAL JOURNAL
(2017)
Article
Biochemical Research Methods
Charles C. David, Ettayapuram Ramaprasad Azhagiya Singam, Donald J. Jacobs
BMC BIOINFORMATICS
(2017)