GB1107 is an orally active inhibitor of galectin-3 (Gal-3; Kd=37nM)[1-2]. GB1107 possesses antiviral and anticancer properties, and is applicable in research related to various tumors such as lung, gastric, and liver cancers and intervertebral disc degeneration[3-4].
In vitro, FTC-133 and 8505C thyroid cancer cells were treated with GB1107 (10–100μM) for 24 hours. By attenuating AKT phosphorylation and downregulating the expression of β-catenin and MMP2, GB1107 significantly inhibited cell adhesion and induced anoikis, while also reducing cell migration and invasion in a dose-dependent manner[5]. Wild-type mouse bone marrow-derived macrophages (WT BMDMs) were pretreated with GB1107 (5μM) for 24 hours, followed by stimulation with LLC tumor cell-conditioned medium (LLC CM). GB1107 enhanced the phagocytic ability of macrophages against tumor cells and suppressed their polarization towards the immunosuppressive M2-like phenotype[6].
In vivo, myeloid cell-specific TIM-3 knock-in mice (FSF-TIM3/LysM-Cre+/-) received intraperitoneal injections of GB1107 (5mg/kg) every other day from 7 weeks of age until 10 weeks of age. GB1107 significantly alleviated lung inflammation and downregulated the transcriptional levels of pulmonary pro-inflammatory cytokines IL-1β and TNF-α[7]. In a CCl₄-induced liver fibrosis model in C57BL/6J mice, GB1107 (10mg/kg) was administered once daily by oral gavage during the final 4 weeks of the model. GB1107 significantly reduced liver fibrosis, evidenced by decreased picrosirius red-stained areas, and lowered plasma markers of liver injury such as ALT and AST[8].
References:
[1] Vuong L, Kouverianou E, Rooney CM, et al. An Orally Active Galectin-3 Antagonist Inhibits Lung Adenocarcinoma Growth and Augments Response to PD-L1 Blockade. Cancer Res. 2019 Apr 1;79(7):1480-1492.
[2] Zetterberg FR, Diehl C, Håkansson M, et al. Discovery of Selective and Orally Available Galectin-1 Inhibitors. J Med Chem. 2023 Dec 28;66(24):16980-16990.
[3] Liu WC, Lin CS, Luo CL, et al. Intracellular Galectin-3 as a Crucial Regulator of Foam Cell Formation and Apoptosis Progression Through the Modulation of Membrane Lipid Rafts. Arch Med Res. 2026 Feb;57(2):103300.
[4] Kim SJ, Kang HG, Kim K, et al. Crosstalk between WNT and STAT3 is mediated by galectin-3 in tumor progression. Gastric Cancer. 2021 Sep;24(5):1050-1062.
[5] Lee JJ, Hsu YC, Li YS, et al. Galectin-3 Inhibitors Suppress Anoikis Resistance and Invasive Capacity in Thyroid Cancer Cells. Int J Endocrinol. 2021 May 7;2021:5583491.
[6] Wang Q, Wu Y, Jiang G, et al. Galectin-3 induces pathogenic immunosuppressive macrophages through interaction with TREM2 in lung cancer. J Exp Clin Cancer Res. 2024 Aug 13;43(1):224.
[7] Kim KS, Lee C, Kim HS, et al. TIM-3 on myeloid cells promotes pulmonary inflammation through increased production of galectin-3. Commun Biol. 2024 Sep 5;7(1):1090.
[8] MacKinnon AC, Humphries DC, Herman K, et al. Effect of GB1107, a novel galectin-3 inhibitor on pro-fibrotic signalling in the liver. Eur J Pharmacol. 2024 Dec 15;985:177077.
GB1107是一种半乳糖凝集素-3（Gal-3；Kd=37nM）抑制剂[1-2]。GB1107具有抗病毒和抑制癌症的作用，可用于肺癌、胃癌、肝癌等多种肿瘤以及COVID-19和椎间盘退变的相关研究[3-4]。
在体外，GB1107（10–100μM）处理甲状腺癌细胞FTC-133和8505C 24小时。GB1107通过减弱AKT磷酸化及下调β-catenin、MMP2的表达，显著抑制细胞粘附性并诱导失巢凋亡，同时以剂量依赖的方式降低细胞的迁移和侵袭能力[5]。GB1107（5μM）预处理野生型小鼠骨髓来源巨噬细胞（WT BMDMs）24小时，随后以LLC肿瘤细胞条件培养基（LLC CM）刺激。GB1107可增强巨噬细胞对肿瘤细胞的吞噬作用，并抑制巨噬细胞向免疫抑制性的M2样表型极化[6]。
在体内，GB1107（5mg/kg）每两天一次腹腔注射，用于处理从7周龄开始直至10周龄的髓系细胞特异性TIM-3敲入小鼠（FSF-TIM3/LysM-Cre+/-）。GB1107显著减轻了肺部炎症，下调了肺部促炎细胞因子IL-1β和TNF-α的转录水平[7]。GB1107（10mg/kg）每日一次口服给药，用于处理在CCl4诱导肝纤维化C57BL/6J小模型4周。GB1107显著减轻了肝脏纤维化，表现为天狼星红染色面积减少，并降低了血浆ALT、AST等肝损伤标志物[8]。