Article
Chemistry, Medicinal
Shuai Wang, Fen-Er Chen
Summary: Inhibition of the MDM2-p53 protein-protein interaction using small-molecule inhibitors is a promising strategy for cancer therapy. Many highly potent and selective small-molecule MDM2 inhibitors have been discovered and are currently undergoing different clinical trials. This review provides an overview of the function of MDM2 and the identification, optimization, preclinical, and clinical studies of clinical-stage MDM2 inhibitors. It also discusses challenges, potential toxicity, and future perspectives, which will guide the design of new small-molecule MDM2 inhibitors.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Nina Komaniecka, Marta Porras, Louis Cairn, Jon Ander Santas, Nerea Ferreiro, Juan Carlos Penedo, Sonia Banuelos
Summary: APE1 is a key enzyme in the BER pathway, involved in repairing oxidative DNA damage. Its structure includes a catalytic domain and a flexible N-terminal extension. Conformational rearrangements occur internally and between molecules when APE1 binds DNA and interacts with NPM1. These findings suggest that the N-terminal region approaches the DNA near the abasic site, and its spatial configuration is sensitive to NPM1, potentially impacting APE1's regulation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Materials Science, Biomaterials
Wan Huang, Jun Zhang, Li Luo, Yao Yu, Taolei Sun
Summary: As an important endogenous signaling molecule, nitric oxide (NO) is involved in various physiological and pathological activities in living organisms. It is proved that NO plays a critical role in tumor therapy, while its short half-life and nonspecific distribution limit its clinical applications. In recent years, progress has been made in developing innovative NO donors, especially smart and multi-modal nanoplatforms, that can precisely control the distribution of therapeutic agents for effective tumor treatment. This review comprehensively discusses the current mechanisms, breakthroughs, and potential of NO-based tumor treatments.
ACS BIOMATERIALS SCIENCE & ENGINEERING
(2023)
Review
Pharmacology & Pharmacy
Hongyu Wu, Hong Yao, Chen He, Yilin Jia, Zheying Zhu, Shengtao Xu, Dahong Li, Jinyi Xu
Summary: Molecular glues can induce protein aggregation to modulate biological functions. They have been used as protein degraders and play important roles in complex stabilization, interactome modulation, and transporter inhibition. Discovering and designing molecular glues systematically is important for drug discovery.
ACTA PHARMACEUTICA SINICA B
(2022)
Review
Pharmacology & Pharmacy
Yi Wang, Qiang Xie, Huidan Tan, Minru Liao, Shiou Zhu, Ling-Li Zheng, Haixia Huang, Bo Liu
Summary: The review discusses epigenetic pathways, small molecule inhibitors targeting DNA methyltransferase and histone modification, as well as combination strategies of existing epigenetic therapeutic drugs to improve efficacy. This sheds light on the discovery of more small-molecule drugs targeting cancer epigenetic pathways as promising strategies for the future.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Chemistry, Multidisciplinary
Si Si Liew, Jia Zhou, Lin Li, Shao Q. Yao
Summary: This study reports the first use of gluthathione-responsive nanogel-based carriers for mitochondria-targeted delivery of functional proteins and antibodies, as well as the successful co-encapsulation of a protein and small molecule (RNase A/Doxorubicin) in dual-cargo nanocapsules for mitochondria-targeted combination therapy.
CHEMICAL COMMUNICATIONS
(2021)
Review
Biochemistry & Molecular Biology
Wan Gi Byun, Donghyun Lim, Seung Bum Park
Summary: This review discusses the potential of targeting PRIs using small molecules, the tools for observing PRIs in biochemical and cell-based experiments, and various PRI modulators. Emerging technologies and challenges in the development of PRI modulators are also highlighted.
CURRENT OPINION IN CHEMICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Rajesh Jaiprashad, Sachith Roch De Silva, Lisette M. Fred M. Lucena, Ella Meyer, Steven J. Metallo
Summary: Intrinsically disordered proteins (IDPs) play important roles in both normal and disease states, and small molecules can target the disordered regions for therapeutic purposes. This study demonstrates the portability of a minimal small-molecule binding sequence in different IDP contexts, as well as the opposing effects of flanking residues on small-molecule binding. These findings shed light on the modular nature of small-molecule binding sites in IDPs.
Article
Chemistry, Medicinal
Yichen Tong, Wentao Zhu, Jian Chen, Tianzhi Wen, Fang Xu, Jiyan Pang
Summary: A series of small-molecule degraders for alpha Syn aggregates were designed and synthesized using probe molecule sery308 as a warhead. Compound 2b showed the highest degradation efficiency with high selectivity. Mechanistic exploration revealed the involvement of both proteasomal and lysosomal pathways in this degradation process. The therapeutic effects of compound 2b were demonstrated in human neuroblastoma cells and Caenorhabditis elegans, expanding the substrate spectrum of PROTAC-based degraders.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Agriculture, Multidisciplinary
Danxia Wu, Li Wang, Wei Li, Xiangyang Li
Summary: This study reports a new insecticide, 3l, targest OBPs and shows that it is more effective in inhibiting the bioactivity of Bemisia tabaci Mediterranean than imidacloprid.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Article
Biophysics
Hansol Kim, Seoyoung Lee, Junhyeok Yoon, Jayeon Song, Hyun Gyu Park
Summary: This study presents a novel method to identify protein/small molecule interactions utilizing the CRISPR/Cas12a system, successfully determining two model interactions at very low concentrations. The technique allows for rapid and simple detection of target proteins by measuring fluorescence signals. The practical applicability of this method was confirmed by reliably detecting target proteins in human serum samples.
BIOSENSORS & BIOELECTRONICS
(2021)
Article
Biochemistry & Molecular Biology
Bing Bai, Rongfeng Zou, H. C. Stephen Chan, Hongchun Li, Shuguang Yuan
Summary: Protein-ligand interaction analysis is crucial for drug discovery and rational protein design. MolADI, an online tool, provides detailed analysis of these interactions and allows easy viewing with 2D graphs and 3D representations. It focuses on interactions that evolve over time.
Article
Cell Biology
Kaili Long, Lili Gu, Lulu Li, Ziyu Zhang, Enjie Li, Yilan Zhang, Lingfeng He, Feiyan Pan, Zhigang Guo, Zhigang Hu
Summary: APE1 plays a critical role in NSCLC and its inhibitor NO.0449-0145 induces DNA damage and cell death, overcoming resistance to traditional chemotherapy in NSCLC cells. These findings highlight the therapeutic potential of targeting APE1 in NSCLC and developing small-molecule drugs for the treatment of other cancers.
CELL DEATH & DISEASE
(2021)
Article
Medicine, Research & Experimental
Fangrui Wu, Shenyou Nie, Yuan Yao, Tong Huo, Xin Li, Xiaowei Wu, Jidong Zhao, Yi-Lun Lin, Yinjie Zhang, Qianxing Mo, Yongcheng Song
Summary: Chromosome translocations involving MLL gene lead to poor-prognosis acute leukemia. Fusion of MLL with transcription cofactors AF4, AF9, or ENL plays a key role in MLL-rearranged leukemia, with AF9/ENL-DOT1L/AF4/AFF4 interactions identified as a potential drug target. Compound-1, a novel inhibitor of these interactions, shows promising antitumor activity and may serve as a pharmacological lead for further drug development in leukemia treatment.
Article
Biochemistry & Molecular Biology
Akinobu Senoo, Satoru Nagatoishi, Daisuke Kuroda, Sho Ito, Go Ueno, Jose M. M. Caaveiro, Kouhei Tsumoto
Summary: Small molecules that regulate protein-protein interactions have potential as valuable drugs. In this study, we propose that modulating the conformational ensemble of the proteins involved in an interaction can interfere with protein-protein interactions. We applied this concept to P-cadherin and found that a small molecule inhibitor modulates the conformational ensemble of P-cadherin, resulting in the inhibition of cell adhesion.
Article
Environmental Sciences
Valentina Roviello, Pasqualina Liana Scognamiglio, Ugo Caruso, Caterina Vicidomini, Giovanni N. Roviello
Summary: This study investigates the potential health benefits of volatile compounds emitted by common houseplants, such as peace lily and iron plant, for indoor forest bathing. The results suggest that these compounds have comparable or even higher anti-COVID-19 potential to known inhibitors and can boost immunity and protect health.
INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
(2022)
Article
Biochemistry & Molecular Biology
Antonio Paolo Beltrami, Maria De Martino, Emiliano Dalla, Matilde Clarissa Malfatti, Federica Caponnetto, Marta Codrich, Daniele Stefanizzi, Martina Fabris, Emanuela Sozio, Federica D'Aurizio, Carlo E. M. Pucillo, Leonardo A. Sechi, Carlo Tascini, Francesco Curcio, Gian Luca Foresti, Claudio Piciarelli, Axel De Nardin, Gianluca Tell, Miriam Isola
Summary: This study identified nine potential serum biomarkers for predicting the severity of COVID-19 by analyzing serum proteins and clinical data. Three of these biomarkers were associated with central nervous system pathologies and protective factors, and were downregulated in the most severe cases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Marta Codrich, Monica Degrassi, Matilde Clarissa Malfatti, Giulia Antoniali, Andrea Gorassini, Dilara Ayyildiz, Rossella De Marco, Giancarlo Verardo, Gianluca Tell
Summary: This study found that APE1 protein is involved in the elimination of damaged RNA after treatment with cisplatin and 5-fluorouracil, and its interaction with MTR4 is stimulated by these treatments. Depletion of APE1 and MTR4 leads to the formation of R-loop structures, which activate the DNA damage response pathway.
Review
Biochemistry & Molecular Biology
Veronica Bazzani, Mara Equisoain Redin, Joshua McHale, Lorena Perrone, Carlo Vascotto
Summary: Mitochondria have their own DNA, which can exist in multiple copies. They have mechanisms to protect and repair DNA damage, as well as specific mechanisms for turnover, fusion, and mitophagy. mtDNA mutations may be common and have effects on aging and neurodegenerative disorders. Analyzing mitochondrial function is crucial for personalized medicine.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Elle E. M. Scheijen, Sven Hendrix, David M. Wilson
Summary: Oxidative stress plays a crucial role in spinal cord injury (SCI), causing damage to proteins, nucleic acids, lipids, cytoskeleton, and organelles. Oxidative DNA damage is likely a major contributor to the pathogenesis of SCI, although the evidence supporting this hypothesis is limited. Improved analysis methods are needed to uncover the role of DNA damage and repair in SCI.
Article
Biochemistry & Molecular Biology
Matilde Clarissa Malfatti, Marta Codrich, Emiliano Dalla, Chiara D'Ambrosio, Francesca Storici, Andrea Scaloni, Gianluca Tell
Summary: The aim of this study is to investigate the existence of modified ribonucleotide monophosphates in genomic DNA under oxidative stress conditions. The research discovered that AUF1 can specifically recognize and promote APE1 endoribonuclease activity on 8-oxo-guanosine embedded in DNA. These findings provide new insights into the genome stability in mammalian cells under oxidative stress-related damages.
ANTIOXIDANTS & REDOX SIGNALING
(2023)
Review
Biochemistry & Molecular Biology
Giuseppe Dall'Agnese, Alessandra Dall'Agnese, Salman F. Banani, Marta Codrich, Matilde Clarissa Malfatti, Giulia Antoniali, Gianluca Tell
Summary: The article summarizes the key features of biomolecular condensates and their potential involvement in repairing DNA double-strand breaks. It also discusses evidence suggesting their role in repairing other types of DNA damage and raises questions that could be addressed considering the properties of condensates, including chemo-resistance mechanisms.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Review
Cell Biology
Matilde Clarissa Malfatti, Alessia Bellina, Giulia Antoniali, Gianluca Tell
Summary: APE1 is an essential endodeoxyribonuclease involved in maintaining genome stability through the base excision repair pathway. It has been identified as a key factor promoting tumor progression and chemoresistance by controlling gene expression through a redox-based mechanism. APE1 is overexpressed and secreted in various cancers, making it a prognostic factor and potential non-invasive biomarker. Inhibition of APE1's functions has shown therapeutic potential, with some inhibitors currently undergoing clinical trials. Additionally, recent evidence suggests novel roles of APE1 in RNA metabolism that are not fully understood, including its involvement in chemoresistant phenotypes, onco-miRNA maturation, and oxidized RNA decay. The discovery of APE1's role in miRNA processing presents new perspectives for personalized cancer therapy.
Article
Gastroenterology & Hepatology
Giovanna Mangiapane, Devis Pascut, Emiliano Dalla, Giulia Antoniali, Monica Degrassi, Lory Saveria Croce, Veronica De Sanctis, Silvano Piazza, Giulia Canarutto, Claudio Tiribelli, Gianluca Tell
Summary: This study investigates the prognostic value of APE1 in HCC and identifies miRNAs regulated by APE1 that are associated with cell proliferation, transformation, and angiogenesis. The overexpression of APE1 in HCC tissues and the correlation between specific miRNAs and lower overall survival in HCC patients are discovered.
JOURNAL OF CLINICAL AND TRANSLATIONAL HEPATOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Giovanna Mangiapane, Isabella Parolini, Kristel Conte, Matilde Clarissa Malfatti, Jessica Corsi, Massimo Sanchez, Agostina Pietrantoni, Vito G. D'Agostino, Gianluca Tell
Summary: The study elucidated the mechanisms by which APE1 is secreted through exosomes and revealed its delivery in response to genotoxic stresses, shedding new light on its noncanonical biological functions in cancer biology.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)