Article
Chemistry, Medicinal
Robert J. Cherney, Prakash Anjanappa, Kumaravel Selvakumar, Douglas G. Batt, Gregory D. Brown, Anne Rose, Ragini Vuppugalla, Jing Chen, Jian Pang, Songmei Xu, Melissa Yarde, Andrew J. Tebben, Venkatram Reddy Paidi, Mary Ellen Cvijic, Arvind Mathur, Joel C. Barrish, Sandhya Mandlekar, Qihong Zhao, Percy H. Carter
Summary: Compound 3, identified as a potent and selective CCR2/5 dual antagonist, demonstrated excellent permeability and stability in vitro, as well as promising pharmacokinetic properties in animal studies, ultimately leading to its selection as a clinical candidate.
ACS MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Medicine, Research & Experimental
Candelaria Vergara, Jeffrey F. Tuff, Jacques Fellay, Priya Duggal, Eileen P. Scully, Paul J. McLaren
Summary: Biological sex and host genetics influence HIV pathogenesis. Females have a higher likelihood of spontaneous viral control and lower set point viral load (spVL). We performed a sex-stratified genome-wide association study using data from the ICGH and identified sex-specific genetic variants and genes associated with HIV spVL and control. These findings provide valuable insights into understanding the role of sex-specific genetics in HIV.
Article
Immunology
Yerkezhan Amerzhanova, Luca Vangelista
Summary: This perspective provides an overview of CCR5 as a central molecular determinant and its potential therapeutic applications. The study focuses on CCR5 antagonism and its impact on receptor-ligand interactions. The analysis of CCL5 mutants reveals the potential for enhanced anti-HIV-1 activity. Furthermore, the exploration of strategies such as improving CCR5 interaction in regions distal to the chemokine N-terminus and developing allosteric antagonists opens up new possibilities for CCR5 blockade.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Medicine, Research & Experimental
Michael R. Ruff, Saadet Inan, Xiang Qun Shi, Joseph J. Meissler, Martin W. Adler, Toby K. Eisenstein, Ji Zhang
Summary: RAP-103, when co-administered with morphine, reduces the dose of morphine required for pain relief and the associated side effects. It also shows effectiveness as a non-opioid treatment for diabetic neuropathic pain.
Article
Immunology
Xiao L. Chang, Helen L. Wu, Gabriela M. Webb, Meenakshi Tiwary, Colette Hughes, Jason S. Reed, Joseph Hwang, Courtney Waytashek, Carla Boyle, Cleiton Pessoa, Andrew W. Sylwester, David Morrow, Karina Belica, Miranda Fischer, Scott Kelly, Nader Pourhassan, Rachele M. Bochart, Jeremy Smedley, Christopher P. Recknor, Scott G. Hansen, Jonah B. Sacha
Summary: CCR5 plays a central role in infectious diseases, host defense, and cancer progression, making it an ideal target for therapeutic development. The study introduces two flow cytometric methods for calculating CCR5 RO, showing sensitivity and correlation in macaques treated with Leronlimab.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Qing-lin Wu, Li-yuan Cui, Wen-yu Ma, Sha-sha Wang, Zhao Zhang, Zhong-ping Feng, Hong-shuo Sun, Shi-feng Chu, Wen-bin He, Nai-hong Chen
Summary: This study characterized the therapeutic potential of a novel CCR5 antagonist A14 in treating ischemic stroke mice. A14 dose-dependently inhibited the CCR5 activity and exerted protective effects against neuronal ischemic injury in vitro and in vivo. Compared to maraviroc, A14 had better BBB permeability and showed sustained protective effects against motor impairment.
ACTA PHARMACOLOGICA SINICA
(2023)
Article
Biochemistry & Molecular Biology
Mastaneh Safarnejad Shad, Sandra Claes, Eline Goffin, Tom Van Loy, Dominique Schols, Steven De Jonghe, Wim Dehaen
Summary: The expansion of the structure-activity relationship study of CXCR4 antagonists led to the synthesis of a series of isoquinolines with excellent activity, among which compound 24c showed consistently low nanomolar activity in various assays and was deemed the most promising.
Article
Biochemistry & Molecular Biology
Maria E. Cardona, Jorma Hinkula, Kristin Gustafsson, Birger Christensson, Britta Wahren, Abdalla J. Mohamed, C. I. Edvard Smith, H. Jose Arteaga
Summary: Treatment with RNAi against HIV-1 transcripts can effectively inhibit viral replication but also leads to the selection of escape mutants. Blocking both viral and host transcripts improves the antiviral effect. The study demonstrates that short hairpin RNA (shRNA) targeting CCR5 provides more sustained protection than shRNA targeting HIV-1 rev. Partial reduction in CCR5 expression significantly decreases HIV-1 infection, and shCCR5 performs better than shRev in mixed treated and untreated cultures.
MOLECULAR BIOLOGY REPORTS
(2022)
Article
Immunology
Anabela C. P. Picton, Maria Paximadis, Gemma W. Koor, Avani Bharuthram, Sharon Shalekoff, Ria Lassauniere, Prudence Ive, Caroline T. Tiemessen
Summary: Our study compared black South African HIV-1 controllers and uninfected healthy controls in terms of lymphocyte and monocyte CCR5 expression, immune activation, and PBMC mitogen-induced chemokine/cytokine production. Despite higher frequencies of activated T cells, controllers had significantly lower CCR5 density in T cell populations, particularly in those with higher viral loads. This suggests a possible genetic predisposition to lower CCR5 expression in individuals who naturally control HIV-1.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Nienke H. van Teijlingen, Julia Eder, Ramin Sarrami-Forooshani, Esther M. Zijlstra-Willems, Jan-Paul W. R. Roovers, Elisabeth van Leeuwen, Carla M. S. Ribeiro, Teunis B. H. Geijtenbeek
Summary: This study assessed the impact of immune activation on the susceptibility of primary human vaginal Langerhans cells (LCs) to HIV-1. It was found that bacterial TLR ligand activation increased HIV-1 infection in immature vaginal LCs, while viral TLR ligands were unable to induce HIV-1 replication. This study highlights the role of vaginal LCs in protecting against mucosal HIV-1 infection and suggests that bacterial STIs can increase the risk of HIV-1 acquisition in women.
SCIENTIFIC REPORTS
(2023)
Review
Immunology
Hager Mohamed, Theodore Gurrola, Rachel Berman, Mackenzie Collins, Ilker K. Sariyer, Michael R. Nonnemacher, Brian Wigdahl
Summary: HIV-1 infection is a global health burden, and current drug therapies face challenges. Novel anti-HIV-1 therapies targeting CCR5 have shown promise in preventing infection and are included in gene editing techniques, CCR5 blockade using antibodies or antagonists, or combinations of both.
FRONTIERS IN IMMUNOLOGY
(2022)
Editorial Material
Biochemistry & Molecular Biology
Jane Y. Chen, Richard D. Palmiter
Summary: In this study, Xie et al. have identified a gut-to-brain pathway that triggers retching after toxic food ingestion or emetic agent administration. Their findings provide insights into how peripheral signals reach the brain to coordinate behavioral responses and facilitate learning to prevent repeated ingestion of harmful substances.
Article
Multidisciplinary Sciences
Jingbo Qiao, Junquan Liu, Jillian C. Jacobson, Rachael A. Clark, Sora Lee, Li Liu, Zhiqiang An, Ningyan Zhang, Dai H. Chung
Summary: Gastrin-releasing peptide receptor (GRP-R) monoclonal antibody (mAb-1) demonstrated effective anti-tumor effects on neuroblastoma cells and may serve as a novel immunotherapy for high-risk neuroblastoma patients.
Article
Chemistry, Organic
Hongshun Yuan, Lei Guo, Xianhua Pan
Summary: An efficient synthetic route for suvorexant without using chiral HPLC separation, resolution, enzyme catalysis or transition metal catalysis is reported, with a total yield up to 37%.
Article
Biochemistry & Molecular Biology
Chengfeng Bai, Shuangjie Wu, Shengnan Ren, Meiqi Zhu, Guoshun Luo, Hua Xiang
Summary: A novel series of covalent antagonists targeting estrogen receptor alpha were designed, synthesized, and evaluated for their antiproliferative efficacy in ER+ breast cancer cells, with compound 19d showing potent antagonistic activity and high selectivity, making it a potential therapeutic option for breast cancer treatment.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
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)