Ting Wei^1,2,#, Pengli Wei^2,3,#, Yalei Wang^1,2, Yaqiu Mao^2,3, Jian Yan², Xiaotong Hu², Zhenze Qi², Xu Cai², Changkai Jia², Zhiyuan Zhao², Bingkun Li², Min Qiao², Yaxin Zou^2,3, Tingting Yang⁴, Shiyang Sun², Xuesong Feng³, Pengyun Li^2,*, Hongzhou Shang^1,*, Zhibing Zheng²

Oncology Research, Vol.33, No.10, pp. 2981-3006, 2025, DOI:10.32604/or.2025.065123 - 26 September 2025

Abstract Objectives: Immunomodulatory drugs (IMiDs), functioning as molecular glue degraders, have been approved for treating various hematological malignancies; however, the inevitable acquired drug resistance resulting from their skeletal similarity and hematological toxicities poses significant obstacles to their clinical treatment. The study aimed to develop degraders with potent efficiency and low toxicity. Methods: Phenotypic profiling, elaborate structure-activity relationships (SAR), rational drug design and degradation profiles investigations, quantitative proteomics analysis and cell-based functional studies, and pharmacokinetic studies were conducted to develop more potent degraders. Results: This study developed novel CRBN-binding moieties through methylene deletion in lenalidomide’s isoindole core. Lead… More > Graphic Abstract

SHUOCHEN PANG¹, TAO JIA^1,*, ZIFENG YANG^2,*

BIOCELL, Vol.48, No.12, pp. 1721-1734, 2024, DOI:10.32604/biocell.2024.055753 - 30 December 2024

Abstract The Receptor for Advanced Glycation End Products (RAGE) is a multiligand receptor of the immunoglobulin superfamily, notably highly expressed in the lungs. Its interaction with a variety of ligands, including advanced glycation end products (AGEs), S100 proteins, and high mobility group box 1 (HMGB1), activates multiple signaling pathways that are pivotal in the pathogenesis of numerous pulmonary diseases and comorbidities. However, comprehensive reviews on the role of ligands-RAGE signaling in specific lung diseases are rare. This review aims to elucidate the mechanisms by which RAGE-mediated signaling pathways either provide protective or pathogenic effects in pulmonary More >

XIAN ZHANG¹, ZHUANG ZHOU², JUNZHE WANG¹, MENGMENG HAN¹, HAN LIU¹, MEIRONG ZANG¹, JIANNING LIU¹, JIAPEI LU¹, JINQIAO ZHANG¹, GUOCHUAN ZHANG^2,*, LIXIA SUN^1,#,*

BIOCELL, Vol.48, No.2, pp. 303-311, 2024, DOI:10.32604/biocell.2023.046640 - 23 February 2024

Abstract Background: Prognosis of multiple myeloma (MM) patients with extramedullary disease (EMD) remains poor. T cell dysfunction and an immunosuppressive environment have been reported in the bone marrow (BM) of MM patients. However, the immunosuppressive microenvironment and immune checkpoint receptors (ICRs) on CD8 T cells in the EMD tissue of newly diagnosed MM (NDMM) patients have not been thoroughly studied. Methods: We investigated the expression levels of T cell immunoglobulin mucin-domain-containing-3 (TIM-3) and T-cell immunoglobulin and ITIM domain (TIGIT) on CD8 T cells and the expression of their ligands (Galectin-9 and CD155) on myeloma cells in… More > Graphic Abstract

XINTONG LIU^1,2,3, EMIKO SANADA^1,3,4, JIANG LI⁵, XIAOMENG LI⁶, HIROYUKI OSADA^1,4,7,*, NOBUMOTO WATANABE^1,2,3,*

Oncology Research, Vol.31, No.5, pp. 645-654, 2023, DOI:10.32604/or.2023.030240 - 21 July 2023

Abstract β-transducin repeat-containing protein (β-TrCP) is an F-box protein subunit of the E3 Skp1-Cullin-F box (SCF) type ubiquitin-ligase complex, and provides the substrate specificity for the ligase. To find potent ligands of β-TrCP useful for the proteolysis targeting chimera (PROTAC) system using β-TrCP in the future, we developed a high-throughput screening system for small molecule β-TrCP ligands. We screened the chemical library utilizing the system and obtained several hit compounds. The effects of the hit compounds on in vitro ubiquitination activity of SCF^β-TrCP1 and on downstream signaling pathways were examined. Hit compounds NPD5943, NPL62020-01, and NPL42040-01 inhibited the… More > Graphic Abstract

Shahriar Dabiri¹, Ashraf Kariminik², Derek Kennedy³

European Cytokine Network, Vol.27, No.2, pp. 16-22, 2016, DOI:10.1684/ecn.2016.0375

Abstract Chemokines and their corresponding receptors serve as pro-inflammatory and migratory signals for immune cells. CXCR3 and its corresponding ligands, CXCL9, CXCL10 and CXCL11, participate in the induction of immune responses against several foreign antigens. Numerous cells, including macrophages, NK cells and T lymphocytes, express CXCR3 and thus, expression of the receptor and its ligands can induce activity of these important immune cells against foreign antigens, including allogeneic grafts. Several parameters of the immune system participate in the induction and stimulation of powerful immune responses against allogeneic grafts. A thorough understanding of the parameters that regulate More >