Article
Biology
Astrid S. Jorgensen, Viktorija Daugvilaite, Katia De Filippo, Christian Berg, Masa Mavri, Tau Benned-Jensen, Goda Juzenaite, Gertrud Hjorto, Sara Rankin, Jon Vabeno, Mette M. Rosenkilde
Summary: Plerixafor exhibits biased action by reversing the CXCL12 gradient across the bone marrow endothelium and showing superior therapeutic effect in HSC mobilization. In contrast, AMD11070, despite having superior antagonism, does not perform as effectively in HSC mobilization in vivo.
COMMUNICATIONS BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Weimin Tang, Sudipta Panja, Chinmay M. Jogdeo, Siyuan Tang, Ao Yu, David Oupicky
Summary: This study investigates the impact of charge and hydrophilicity of polymers on their accumulation in injured kidneys and demonstrates that polymers with hydroxyl group modification show the least accumulation. These findings provide important guidance for the development of targeted drug carriers for AKI therapy.
Article
Pharmacology & Pharmacy
Isabel Hamshaw, Marco M. D. Cominetti, Wing-Yee Lai, Mark Searcey, Anja Mueller
Summary: Cancer metastasis is a major cause of cancer-related death. The CXCR4 receptor and its ligand CXCL12 play important roles in promoting metastasis, making them attractive therapeutic targets. In this study, a novel CXCR4 antagonist was developed and used for CXCR4-based imaging. The results showed that these antagonists were non-toxic and effectively inhibited cancer cell migration and calcium release.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Medicine, General & Internal
Pitchaya P. Indravudh, Katherine Fielding, Moses K. Kumwenda, Rebecca Nzawa, Richard Chilongosi, Nicola Desmond, Rose Nyirenda, Melissa Neuman, Cheryl C. Johnson, Rachel Baggaley, Karin Hatzold, Fern Terris-Prestholt, Elizabeth L. Corbett
Summary: The study conducted in a rural, high HIV prevalence area of Malawi found that community-led delivery of HIV self-testing (HIVST) was effective, safe, and affordable in increasing HIV testing and ART initiation rates. The intervention rapidly achieved high impact and coverage at low cost, with great potential for economies of scale and scope. Community-led HIVST should be considered by national HIV programmes in priority settings for periodic community testing to achieve HIV elimination goals, utilizing established community health groups widely available in sub-Saharan Africa.
Article
Chemistry, Multidisciplinary
Zhonghua Sun, Jie Yao, Shuliang Ji, Weiyou Zhou, Anwei Wang, Mingyang He, Xianjun Hua, Yupeng Liu
Summary: FeCl2/TBAC was found to exhibit high catalytic activity for the synthesis of indoline-fused tetrahydroisoquinolines using aryltetrahydroisoquinolines and active methylene as reactants. The reaction proceeded through domino coupling reactions between C-sp3-H and C-sp3-H, and subsequently C-sp3-H and C-sp2-H. EPR spectroscopy revealed the presence of catalytically active species (Fe3+OO center dot) and Fe3+, which enhanced the reaction through HAT and SET processes, respectively.
NEW JOURNAL OF CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Sebastian Dekkers, Birgit Caspar, Joelle Goulding, Nicholas D. Kindon, Laura E. Kilpatrick, Leigh A. Stoddart, Stephen J. Briddon, Barrie Kellam, Stephen J. Hill, Michael J. Stocks
Summary: In this study, fluorescent probes based on previously reported small-molecule antagonists were designed and synthesized using classic medicinal chemistry approaches to investigate the pharmacology and cellular distribution of the CXCR4 receptor. Three distinct chemical classes of fluorescent probes were developed and shown to specifically bind to the CXCR4 receptor in a fluorescence-based NanoBRET binding assay (pKD ranging 6.6-7.1). These probes were also used in competition binding experiments and confocal microscopy to further explore the pharmacology and cellular distribution of CXCR4.
JOURNAL OF MEDICINAL CHEMISTRY
(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
Medicine, General & Internal
Michelle N. Rheault, Charles E. Alpers, Jonathan Barratt, Stewart Bieler, Pietro Canetta, Dong-Wan Chae, Gaia Coppock, Ulysses Diva, Loreto Gesualdo, Hiddo J. L. Heerspink, Jula K. Inrig, Gianna M. Kirsztajn, Donald Kohan, Radko Komers, Laura A. Kooienga, Kenneth Lieberman, Alex Mercer, Irene L. Noronha, Vlado Perkovic, Jai Radhakrishnan, William Rote, Brad Rovin, Vladimir Tesar, Hernan Trimarchi, James Tumlin, Muh Geot Wong, Howard Trachtman, DUPRO Steering Comm, DUPLEX Investigators
Summary: In the treatment of FSGS, sparsentan showed a better reduction in proteinuria compared to irbesartan. However, there were no significant differences in eGFR slope between the two groups at 108 weeks. Both sparsentan and irbesartan demonstrated similar safety profiles.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Zachary D. Crees, Michael P. Rettig, Reyka G. Jayasinghe, Keith Stockerl-Goldstein, Sarah M. Larson, Illes Arpad, Giulio A. Milone, Massimo Martino, Patrick Stiff, Douglas Sborov, Denise Pereira, Ivana Micallef, Gemma Moreno-Jimenez, Gabor Mikala, Maria Liz Paciello Coronel, Udo Holtick, John Hiemenz, Muzaffar H. Qazilbash, Nancy Hardy, Tahir Latif, Irene Garcia-Cadenas, Abi Vainstein-Haras, Ella Sorani, Irit Gliko-Kabir, Inbal Goldstein, Debby Ickowicz, Liron Shemesh-Darvish, Shaul Kadosh, Feng Gao, Mark A. Schroeder, Ravi Vij, John F. DiPersio
Summary: Autologous hematopoietic stem cell transplantation (ASCT) improves survival in multiple myeloma (MM). Motixafortide combined with G-CSF significantly improves the collection of CD34(+) hematopoietic stem cells compared to G-CSF alone. Motixafortide + G-CSF demonstrates superior efficacy in ASCT.
Article
Immunology
Xiaoyan Hu, Yi Feng, Kang Li, Yueyang Yu, Abdur Rashid, Hui Xing, Yuhua Ruan, Lingling Lu, Min Wei, Yiming Shao
Summary: CRF07_BC is a prevalent HIV-1 strain in China, characterized by predominantly single CCR5 tropism. This study found evidence that CRF07_BC has the ability to evolve into CXCR4 strains.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Devki D. Sukhtankar, Juan Jose Fung, Mi-na Kim, Thomas Cayton, Valerie Chiou, Nina G. Caculitan, Piotr Zalicki, Sujeong Kim, Yoonjung Jo, SoHui Kim, Jae Min Lee, Junhee Choi, SeongGyeong Mun, Ashley Chin, Yongdae Jang, Ji Yeong Lee, Gowoon Kim, Eun Hee Kim, Won-Ki Huh, Jae-Yeon Jeong, Dong-Seung Seen, Pina M. Cardarelli
Summary: Autologous Stem Cell Transplant (ASCT) is a common method for treating hematological malignancies. The combination of G-CSF and GPC-100 shows potential for sufficient and rapid collection of stem cells.
Article
Oncology
Max Czajkowski, Daniel Kaemmerer, Joerg Saenger, Guido Sauter, Ralph M. Wirtz, Stefan Schulz, Amelie Lupp
Summary: This study analyzed the expression of SSTs and CXCR4 in thyroid carcinomas and found low and variable expression levels. The expression of SST3, SST4, SST5, and CXCR4 was correlated with proliferation and survival rates in thyroid cancer. Therefore, SST- or CXCR4-based diagnostics or therapy may be feasible in individual cases with high expression of these receptors.
Article
Chemistry, Medicinal
Raghuvir Haridas Gaonkar, Yannik Tim Schmidt, Rosalba Mansi, Yasser Almeida-Hernanadez, Elsa Sanchez-Garcia, Mirja Harms, Jan Muench, Melpomeni Fani
Summary: The peptide fragment of human serum albumin, EPI-X4, was investigated as a scaffold for CXCR4-targeted radiotheragnostics. Ligand-7 (JM#21 derivative) showed the best CXCR4-tumor targeting and low uptake in non-targeted organs. These findings support the feasibility of using EPI-X4-based radioligands for CXCR4 targeting with ligand-7 as a lead candidate for further optimization.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Chemistry, Medicinal
Joana Gorica, Maria Silvia De Feo, Ferdinando Corica, Marko Magdi Abdou Sidrak, Miriam Conte, Luca Filippi, Orazio Schillaci, Giuseppe De Vincentis, Viviana Frantellizzi
Summary: This systematic review focuses on the clinical and preclinical applications of the CCR4 receptor as a target for theranostics. The review provides a comprehensive overview of CCR4 expression and its role in various tumors. The study finds that the development of new radionuclides and radiopharmaceuticals targeting CCR4 shows promising results in the theranostics of CCR4-sensitive tumors. However, further translation of preclinical to clinical data is needed to expand its use in clinical practice.
Article
Virology
Ruohan Zhu, Xiaohong Sang, Jiao Zhou, Qian Meng, Lina S. M. Huang, Yan Xu, Jing An, Ziwei Huang
Summary: Human immunodeficiency virus-1 (HIV-1) uses the third variable loop (V3 loop) of its envelope glycoprotein gp120 to recognize the coreceptor CXCR4 on host cells during viral entry. Synthetic peptides containing the full-length V3 loop were used to investigate the molecular recognition mechanism between HIV-1 gp120 V3 loop and CXCR4. The results show that the cyclic L- and D-V3 loop peptides have comparable binding to CXCR4 and selectively interact with it, indicating the flexibility of the HIV-1 gp120 V3 loop-CXCR4 interface for ligands with different chiralities.