Article
Oncology
Dipakkumar R. Prajapati, Caitlin Molczyk, Abhilasha Purohit, Sugandha Saxena, Reegan Sturgeon, Bhavana J. Dave, Sushil Kumar, Surinder K. Batra, Rakesh K. Singh
Summary: Pancreatic cancer (PC) has a poor prognosis, and targeting CXCR2/1 using small molecule inhibitors shows promise in inhibiting PC growth, angiogenesis, and metastasis. In this study, the therapeutic utility of the CXCR2/1 antagonist SCH-479833 was evaluated in different PC murine models, demonstrating antitumor and anti-metastatic effects. CXCR2/1 antagonist treatment inhibited tumor cell proliferation, migration, angiogenesis, and neutrophil recruitment, while promoting apoptosis, fibrosis, tumor necrosis, and extramedullary hematopoiesis. These findings suggest that selectively targeting CXCR2/1 with small molecule inhibitors is a promising therapeutic approach for PC.
Review
Pharmacology & Pharmacy
Kawthar Dhayni, Kazem Zibara, Hawra Issa, Said Kamel, Youssef Bennis
Summary: CXCR1 and CXCR2 chemokine receptors are critical in inflammation, and CXCR1/2 inhibitors show beneficial effects in preventing cardiovascular disease progression.
PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Chemistry, Physical
Haiyan Yang, Zheyuan Shen, Linxiang Luo, Jian Gao, Sikang Chen, Jinxin Che, Lei Xu, Meijuan Wu, Xiaowu Dong
Summary: CXC chemokine receptors 1 (CXCR1) and 2 (CXCR2), members of the GPCRs family, play important roles in cancer cell proliferation, apoptosis, and angiogenesis. The high sequence homology between CXCR1 and CXCR2 poses a challenge in developing selective antagonists. Through computational methods, it was discovered that the differences in the amino acids ASN311 on CXCR1 and LYS320 on CXCR2 are the main reason for the different antagonistic abilities of CXCR1/2, providing important clues for the development of selective CXCR1/2 antagonists.
CHEMICAL PHYSICS LETTERS
(2022)
Article
Oncology
Paola Verachi, Francesca Gobbo, Fabrizio Martelli, Andrea Martinelli, Giuseppe Sarli, Andrew Dunbar, Ross L. Levine, Ronald Hoffman, Maria Teresa Massucci, Laura Brandolini, Cristina Giorgio, Marcello Allegretti, Anna Rita Migliaccio
Summary: This study demonstrates that Reparixin treatment can reduce fibrosis in a mouse model of myelofibrosis by decreasing the expression of TGF-beta 1 and collagen III while increasing the expression of GATA1. These findings provide a preclinical rationale for further evaluating the use of Reparixin in the treatment of patients with myelofibrosis.
FRONTIERS IN ONCOLOGY
(2022)
Review
Chemistry, Medicinal
Yishi Xie, Wenbin Kuang, Dawei Wang, Kai Yuan, Peng Yang
Summary: C-X-C motif chemokine receptor 2 (CXCR2) is a G protein-coupled receptor (GPCR) that is involved in various inflammatory diseases and cancers. It is closely associated with the migration of neutrophils and monocytes. Small-molecule CXCR2 antagonists have shown promising safety and therapeutic effects in clinical trials. CXCR2 could potentially serve as a biomarker and therapeutic target for diabetes, and CXCR2 antagonists may also have a role in attenuating lung injury in COVID-19.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Fisheries
Beibei Zhao, Jing Diao, Le Li, Hidehiro Kondo, Lei Li, Ikuo Hirono
Summary: This study identified and characterized the CXCR2 gene in Japanese flounder, showing that the expression levels of JfCXCR1 and JfCXCR2 increase significantly in response to bacterial infections, with JfCXCR1 potentially activated by bacterial infections and JfCXCR2 activated by both bacterial and viral infections to mediate the immune response. These findings contribute to understanding the functions of CXCR1 and CXCR2 in the fish immune system.
DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
(2021)
Article
Chemistry, Medicinal
Max E. E. Huber, Silas Wurnig, Lara Toy, Corinna Weiler, Nicole Merten, Evi Kostenis, Finn K. K. Hansen, Matthias Schiedel
Summary: In this study, a fluorescent ligand targeting the intracellular allosteric binding site (IABS) of CXCR2 was developed. The ligand, Mz438 (9a), exhibited high affinity and selectivity and could be used for visualizing intracellular target engagement. This fluorescent ligand represents a promising tool for future studies of CXCR2 pharmacology.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Cell & Tissue Engineering
Adeline Blandinieres, Xuechong Hong, Aurelien Philippe, Ivan Bieche, Sophie Vacher, Elisa Rossi, Gregoire Detriche, Nicolas Gendron, Pascale Gaussem, Coralie L. Guerin, Juan M. Melero-Martin, David M. Smadja
Summary: Studies have investigated the presence of CXCR1 and CXCR2 receptors on ECFCs, finding that these receptors were not detected. In addition, comparison of RT-PCR primers used to search for CXCR1 and CXCR2 mRNA revealed potential non-specific DNA amplification.
STEM CELL REVIEWS AND REPORTS
(2021)
Review
Oncology
Jan Korbecki, Patrycja Kupnicka, Katarzyna Barczak, Mateusz Bosiacki, Pawel Zietek, Dariusz Chlubek, Irena Baranowska-Bosiacka
Summary: AML is a type of leukemia with a poor prognosis. This review focuses on the significance of CXC chemokines other than CXCL12 in AML, including their roles in AML tumor processes, clinical relevance, and association with other factors such as chemoresistance and bone marrow angiogenesis. The aim of this study is to provide an overview of the less-studied CXC chemokine axes in AML and bridge the gap in current research.
Article
Chemistry, Organic
Zhongxue Fang, Yujie Zhang, Hongwei Wang, Giuseppe Zanoni, Jianxin Li, Xingqi Li, Zhaohong Liu, Yongquan Ning
Summary: A metal-free cycloaddition reaction of fluoroalkyl N-sulfonylhydrazones with arene-diazonium salts to form fluoroalkylated tetrazole products was reported. This procedure provides a general and safe method for accessing mono-, di-, and perfluoroalkyl tetrazoles with excellent yields and tolerance of diverse functional groups.
ORGANIC CHEMISTRY FRONTIERS
(2022)
Article
Oncology
Geny Piro, Carmine Carbone, Antonio Agostini, Annachiara Esposito, Maria De Pizzol, Rubina Novelli, Marcello Allegretti, Andrea Aramini, Alessia Caggiano, Alessia Granitto, Francesco De Sanctis, Stefano Ugel, Vincenzo Corbo, Maurizio Martini, Rita Teresa Lawlor, Aldo Scarpa, Giampaolo Tortora
Summary: This study evaluated the effectiveness of combining a CXCR1/2 inhibitor with anti-PD-1 in treating immunosuppression in PDAC. The results showed that this combination therapy can reverse M2 macrophage polarization, reduce tumor burden, and improve the efficacy of immunotherapy.
BRITISH JOURNAL OF CANCER
(2023)
Article
Biochemistry & Molecular Biology
Klaudia Szymczak, Margery G. H. Pelletier, James M. Mackay, DeAnne Reid, Peter C. W. Gaines
Summary: Neutrophils are important regulators of innate immunity, and a small molecule antagonist called RIST4721 can effectively inhibit their chemotaxis in ex vivo-cultured mouse bone marrow cells stimulated by KC. RIST4721-treated neutrophils exhibited enhanced phagocytosis and reactive oxygen species production, confirming the specificity of the drug. These findings suggest that RIST4721 could be a potential treatment for various inflammatory conditions mediated by neutrophils.
Article
Oncology
Pat Gulhati, Aislyn Schalck, Shan Jiang, Xiaoying Shang, Chang-Jiun Wu, Pingping Hou, Sharia Hernandez Ruiz, Luisa Solis Soto, Edwin Parra, Haoqiang Ying, Jincheng Han, Prasenjit Dey, Jun Li, Pingna Deng, Emi Sei, Dean Y. Maeda, John A. Zebala, Denise J. Spring, Michael Kim, Huamin Wang, Anirban Maitra, Dirk Moore, Karen Clise-Dwyer, Y. Alan Wang, Nicholas E. Navin, Ronald A. DePinho
Summary: Pancreatic ductal adenocarcinoma (PDAC) is resistant to PD1 and CTLA4 immune checkpoint therapies. This study characterized the mechanisms of ICT resistance and identified effective therapeutic options. The combination of agonist 41BB and antagonist LAG3 ICT increased survival and antitumor immunity. Triple therapy with T cell-activating ICTs and a CXCR1/2 inhibitor resulted in durable complete responses. This provides a testable hypothesis for clinical testing in human PDAC.
Article
Dermatology
S. Arikan, A. Atalay, O. Ozturk, S. Duygulu, E. O. Atalay
Summary: This study found that the CXCR2 rs2230054 TT genotype and the CXCL5 rs352046 polymorphism might be associated with Behcet disease. However, no association was found between the development of BD and the four CXCR1 polymorphisms or the other two CXCR2 SNPs. Haplotype analysis results also indicated differences in haplotypes of the CXCR2 and CXCR1-CXCR2 polymorphic loci between BD and HC groups.
CLINICAL AND EXPERIMENTAL DERMATOLOGY
(2021)
Article
Endocrinology & Metabolism
Lorenzo Piemonti, Bart Keymeulen, Pieter Gillard, Thomas Linn, Emanuele Bosi, Ludger Rose, Paolo Pozzilli, Francesco Giorgino, Efisio Cossu, Luisa Daffonchio, Giovanni Goisis, Pier Adelchi Ruffini, Anna Rita Maurizi, Flavio Mantelli, Marcello Allegretti
Summary: The study aimed to evaluate the effects of ladarixin (LDX) on sustaining C-peptide production in newly diagnosed type 1 diabetes patients. The results showed that short-term LDX treatment had no significant impact on preserving residual beta cell function, but there were transient metabolic benefits in some secondary endpoints.
DIABETES OBESITY & METABOLISM
(2022)
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)