Review
Medicine, Research & Experimental
Xianbo Wu, Jie Wang, Qi Liang, Rongsheng Tong, Jianli Huang, Xinwei Yang, Yihua Xu, Wenjing Wang, Minghan Sun, Jianyou Shi
Summary: FAK is an important target for cancer treatment, and many small molecule inhibitors have shown efficacy in inhibiting tumor growth and metastasis. Dual inhibitors that block FAK and other factors simultaneously can improve therapeutic efficacy and overcome drug resistance.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Biology
Duangjai Todsaporn, Panupong Mahalapbutr, Rungtiva P. Poo-arporn, Kiattawee Choowongkomon, Thanyada Rungrotmongkol
Summary: In this study, the effects of EGFR mutations on the susceptibility of different EGFR inhibitors were investigated using comprehensive molecular modeling and in vitro kinase inhibition assays. The results showed that three hot-spot residues were involved in the binding of osimertinib and afatinib to mutated EGFRs, enhancing their inhibitory activity. Furthermore, principal component analysis revealed that the molecular complexation of osimertinib against mutated EGFRs was in a closed conformation, leading to drug resistance.
COMPUTERS IN BIOLOGY AND MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Gayathri Shama Bhat, Fayaz Shaik Mohammad
Summary: By analyzing phytochemicals from plants with established records in treating brain disorders, novel compounds were computationally designed and predicted to have potential as inhibitors of EGFR, even in cases of drug-resistance mutations.
CHEMISTRY & BIODIVERSITY
(2023)
Article
Pharmacology & Pharmacy
Su-Pei Wang, Ya-Ping Hsu, Chien-Jen Chang, Yu-Chi Chan, Chien-Hung Chen, Rou-Hsin Wang, Kuang-Kai Liu, Pei-Ying Pan, Ya-Hui Wu, Chih-Man Yang, Chinpiao Chen, Jinn-Moon Yang, Mei-Chih Liang, Kwok-Kin Wong, Jui- Chao
Summary: SP101, a novel synthetic compound derived from gefitinib, inhibits survivin expression and tumor growth in both EGFR-wild type and EGFR-T790M of NSCLC, showing promise as a potential treatment for gefitinib-resistant lung cancers with different EGFR mutations.
BIOCHEMICAL PHARMACOLOGY
(2021)
Review
Pharmacology & Pharmacy
Hee-Jeong Choi, Yoo Joo Jeong, Jieun Kim, Hyang-Sook Hoe
Summary: Many researchers are exploring the repurposing of epidermal growth factor receptor (EGFR) inhibitors, commonly used as anti-cancer drugs, as potential therapies for Alzheimer's disease (AD). Studies have shown that these inhibitors can attenuate AD pathology and improve cognitive function in mouse models. This review discusses the functions of EGFR in both cancer and AD, and highlights the significance of EGFR as a molecular target for these diseases.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Plant Sciences
Xiaozhuo Tan, Meiling Le, Haiwen Wang, Bitao Huo, Tiantian Yu, Peng Huang, Tiangang Luan, Shijun Wen
Summary: This study reports the design and synthesis of novel peptide-drug conjugates (PDCs) that bind to both the extracellular and intracellular domains of epidermal growth factor receptor (EGFR). One peptide motif interacts with the extracellular domain, while the other motif derived from an EGFR inhibitor occupies the intracellular kinase domain. Among the synthetic PDCs, compound 14c shows the best inhibition of EGFR phosphorylation and the ability to inhibit cell proliferation and colony formation in lung cancer cells. This study provides a novel strategy to develop more potent EGFR inhibitors by targeting both extracellular and intracellular domains simultaneously.
PHYTOCHEMISTRY LETTERS
(2023)
Article
Multidisciplinary Sciences
Tereza Vaclova, Ursula Grazini, Lewis Ward, Daniel O'Neill, Aleksandra Markovets, Xiangning Huang, Juliann Chmielecki, Ryan Hartmaier, Kenneth S. Thress, Paul D. Smith, J. Carl Barrett, Julian Downward, Elza C. de Bruin
Summary: T790M subclonality is associated with poorer response to osimertinib and shorter progression-free survival, likely due to co-occurring PIK3CA alterations which can be targeted by PI3K pathway inhibitors.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Avinash Kumar, Sudhanshu Rai, Ekta Rathi, Paridhi Agarwal, Suvarna G. Kini
Summary: The study presents a pharmacophore-guided fragment-based design strategy for developing novel mTOR inhibitors. Designed molecules showed good binding affinity at both sites, with one molecule identified to have the highest predicted activity. The report introduces five potential mTOR dual inhibitors based on predicted activity and drug-likeness analysis.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Biochemistry & Molecular Biology
Jiaming Gao, Yunying Yao, Chenxuan Liu, Xi Xie, Donghe Li, Ping Liu, Zaiqi Wang, Baoyuan Zhang, Ruibao Ren
Summary: CDH1 deficiency is common in diffuse gastric cancer and triple negative breast cancer patients. Inhibition of ROS1 results in synthetic lethality in CDH1-deficient cancers, but often leads to adaptive resistance. Upregulation of FAK activity is observed in gastric and breast CDH1-deficient cancers upon resistance to ROS1 inhibitor therapy. FAK inhibition enhances the cytotoxicity potency of ROS1 inhibitor in CDH1-deficient cancer cell lines.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Xin Wu, Yuan Zhang, Songbin Liu, Chang Liu, Guotao Tang, Xuan Cao, Xiaoyong Lei, Junmei Peng
Summary: Fragment-based drug discovery is gaining momentum in academia, large pharmaceutical companies, and biotechnology laboratories as a complementary method to traditional screening. It involves selecting favorable combinations of fragments or extending new drug molecules to obtain highly active drug candidates. This article highlights different types and classifications of linkers published in the past decade, explaining how these linkers are designed and introduced into lead compounds to obtain potential candidate compounds.
BIOORGANIC CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Phoebe F. Lamie, Asmaa M. El-Kalaawy, Noha S. Abdel Latif, Laila A. Rashed, John N. Philoppes
Summary: A new series of compounds were designed and evaluated for their antitumor and anticonvulsant activities in cell lines and animal models, showing promising effects and mechanisms.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemical Research Methods
Camille M. Le Gall, Johan M. S. van der Schoot, Ivan Ramos-Tomillero, Melek Parlak Khalily, Floris J. van Dalen, Zacharias Wijfjes, Liyan Smeding, Duco van Dalen, Anna Cammarata, Kimberly M. Bonger, Carl G. Figdor, Ferenc A. Scheeren, Martijn Verdoes
Summary: Functionalized antibodies and antibody fragments play important roles in biomedical imaging, theranostics, and antibody-drug conjugates. This study describes a CRISPR/Cas9-based strategy to engineer hybridoma cells to secrete Fab' fragments bearing two distinct site-specific labeling motifs, enabling the generation of a stable cell line that secretes a dual tagged Fab' molecule. The technology platform developed in this study has the potential to advance the development of multimodal imaging agents, theranostics, and next-generation ADCs.
BIOCONJUGATE CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Manon Garcia, Laurent Hoffer, Raphael Leblanc, Fatiha Benmansour, Mikael Feracci, Carine Derviaux, Antonio Luis Egea-Jimenez, Philippe Roche, Pascale Zimmermann, Xavier Morelli, Karine Barral
Summary: Syntenin stimulates exosome production and is implicated in cancer metastasis. Through fragment-based drug design, novel inhibitors targeting syntenin-syndecan interactions were developed. Optimization of a fragment led to the discovery of compounds that selectively affect syntenin-exosome release.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Chemistry, Medicinal
Jun Ge, Yu Yin, Yingpeng Li, Yanru Deng, Hui Fu
Summary: This review summarizes the research progress in dual-target inhibitors based on PARP1 and discusses the related drug design strategies and structure-activity relationships.
FUTURE MEDICINAL CHEMISTRY
(2022)
Review
Medicine, Research & Experimental
Qingqing Pan, Yao Lu, Li Xie, Di Wu, Rong Liu, Wenxia Gao, Kui Luo, Bin He, Yuji Pu
Summary: Epidermal growth factor receptor (EGFR) is essential for cell proliferation, growth, and survival. Its abnormal activation and overexpression are associated with poor prognosis and short survival in malignancy. Inhibition of EGFR by tyrosine kinase inhibitors (TKIs) has become an important treatment model in addition to chemotherapy, but it still has challenges such as off-target toxicity, limited cancer types, and drug resistance.
MOLECULAR PHARMACEUTICS
(2023)
Correction
Biochemistry & Molecular Biology
Mohamed Marzouk, Shimaa M. Khalifa, Amal H. Ahmed, Ahmed M. Metwaly, Hala Sh. Mohammed, Hanan A. A. Taie
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Gerardo Andres Libreros-Zuniga, Danilo Pava e Pavao, Vinicius de Morais Barroso, Nathalya Cristina de Moraes Roso Mesquita, Saulo Fehelberg Pinto Braga, Glaucius Oliva, Rafaela Salgado Ferreira, Kelly Ishida, Marcio Vinicius Bertacine Dias
Summary: Tuberculosis is a major global cause of death, and the emergence of drug-resistant strains has increased the burden of this disease. New alternative therapies are constantly needed, and recent research has identified small molecules as potential inhibitors of Ldts in M. tuberculosis, which have antimycobacterial activity.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Xiao-Dong Wang, Yong-Si Liu, Ming-Hao Hu
Summary: In this study, a selffolded fluorescent probe was designed to selectively illuminate G4s by unfolding its intramolecular aggregation mediated by G4 binding. This probe showed more controllable background emission and promising ability to track G4 forming dynamics compared to previous disaggregation-induced emission (DIE) probes.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Yu Xiang, Zhuo Yuan, Qichuan Deng, Linshen Xie, Dongke Yu, Jianyou Shi
Summary: This review provides a brief description of the diagnosis, pathogenesis, and potential therapeutic inhibitors for renal fibrosis. Currently, there are no clear therapeutic targets or drugs for renal fibrosis; however, some natural products may have potential efficacy for treating renal fibrosis.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Simone Giovannuzzi, Anna Nikitjuka, Bruna Rafaela Pereira Resende, Michael Smietana, Alessio Nocentini, Claudiu T. Supuran, Jean-Yves Winum
Summary: Boron-based compounds have been extensively studied in medicinal chemistry, playing a crucial role in designing small molecule drugs for various diseases. Boron is particularly valuable in developing inhibitors for metalloenzymes carbonic anhydrases, and it can modulate ligand recognition ability and selectivity. Recent advancements have led to the discovery of novel boron-based inhibitors that can inhibit carbonic anhydrases through a Lewis acid-base mechanism. Further research is needed to fully explore the potential of boron-based inhibitors and advance their clinical applications.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Xinxin Liu, Lei Chen, Ze Chen
Summary: This study developed a nanostructured photosensitizer loaded with oxygen-throttling drug and demonstrated its enhanced cytotoxicity against tumor cells under hypoxic conditions. Animal experiments showed the enhanced tumor targeting capability of the photosensitizer and its inhibitory effect on tumor growth.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Shuai Jiang, Wen-Yan Li, Zai-Feng Yuan, Qin-Shi Zhao
Summary: This study isolated two new dimeric Lycopodium alkaloids and twelve previously undescribed Lycopodium alkaloids from Lycopodiastrum casuarinoides. The structures of these compounds were determined and their inhibitory activities on the Cav3.1 channel were evaluated.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Yan Yang, Dong-Xiao Yan, Rui-Xue Rong, Bing-Ye Shi, Man Zhang, Jing Liu, Jie Xin, Tao Xu, Wen-Jie Ma, Xiao-Liu Li, Ke-Rang Wang
Summary: In this study, a series of nucleolar fluorescent probes based on naphthalimide derivatives were designed and synthesized, which could achieve clear nucleolar staining in living cells. The results showed that these probes exhibited good targeting to the cell nucleolus and could bind to RNA and enhance fluorescence. This has positive implications for the diagnosis and treatment of nucleolus-related diseases.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Yongxi Dong, Fang Wang, Jinlan Wen, Yongqing Mao, Shanhui Zhang, Tiemei Long, Zhangxiang Yang, Lei Li, Jiquan Zhang, Li Dong, Gang Liu, Jianwei Xu
Summary: The hybrid molecules of Scutellarein and Tertramethylpyrazine show excellent neuroprotective and antiplatelet effects in the treatment of ischemic stroke. Compound 1e is particularly effective, enhancing cell membrane permeability and inhibiting cell uptake, as well as significantly reducing cerebral infarction volume.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Yu Chen, Yuanyuan Ying, Jonathan Lalsiamthara, Yuheng Zhao, Saber Imani, Xin Li, Sijing Liu, Qingjing Wang
Summary: This paper examines the role and metabolic regulation of NAD+ in bacteria, highlighting its impact on physiology and virulence. It explores enzymes associated with NAD+ metabolism as potential targets for antibacterial drugs and vaccine candidates. Additionally, it scrutinizes the medical potential of NAD+ and provides insights for its application in biomedicine.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Jon Macicior, Daniel Fernandez, Silvia Ortega-Gutierrez
Summary: Hutchinson-Gilford progeria syndrome (HGPS), also known as progeria, is a rare genetic disease that causes premature aging and significantly reduces life expectancy. Currently, there is only one approved drug for treating progeria, but its efficacy is limited. Progerin levels are believed to be the most important biomarker related to disease severity.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Fuko Hirano, Naoya Kondo, Yusuke Murata, Aya Sudani, Takashi Temma
Summary: Fluorinated alpha-methyl 3BPA derivatives showed improved water solubility, tumor targetability, and biodistribution compared to 3BPA and BPA, resulting in significantly improved tumor-to-normal tissue ratios.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Ying Shi, Jiaqin Tang, Shumeng Zhi, Ruiqi Jiang, Qing Huang, Lei Sun, Zhizhong Wang, Yanran Wu
Summary: Necroptosis is a type of cell death associated with various diseases. In this study, we identified a small molecule inhibitor, SY-1, that effectively blocks necroptosis by inhibiting the phosphorylation of RIP1/RIP3/MLKL pathway. SY-1 also showed protective effects against TNF-induced hypothermia and improved survival in mice with SIRS. These findings highlight the potential therapeutic applications of SY-1.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Andrea Bagan, Sonia Abas, Judith Pala-Pujadas, Alba Irisarri, Christian Grinan-Ferre, Merce Pallas, Itziar Muneta-Arrate, Carolina Muguruza, Luis F. Callado, Belen Perez, Elies Molins, Jose A. Morales-Garcia, Carmen Escolano
Summary: Recent studies have identified the modulation of imidazoline I-2 receptors (I-2-IR) by selective ligands as a potential strategy for treating neurodegenerative diseases. This study reports a family of bicyclic alpha-iminophosphonates that show high affinity and selectivity for I-2-IR and demonstrates their neuroprotective and anti-inflammatory effects in in vitro and in vivo models. The findings emphasize the importance of exploring structurally novel I-2-IR ligands for therapeutic strategies in neurodegeneration.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Qiuping Xiang, Tianbang Wu, Cheng Zhang, Chao Wang, Hongrui Xu, Qingqing Hu, Jiankang Hu, Guolong Luo, Xiaoxi Zhuang, Xishan Wu, Yan Zhang, Yong Xu
Summary: This study reports the discovery of a 1-(indolizin-3-yl)ethan-1-one derivative as a potent and selective CBP bromodomain inhibitor for AML drug development.
BIOORGANIC CHEMISTRY
(2024)