GLPG0187 is a broad-spectrum integrin receptor antagonist that exhibits selectivity for various integrin receptors, with the following IC50 values: αVβ1 at 1.3nM, αVβ3 at 3.7nM, αVβ5 at 2.0nM, αVβ6 at 1.4nM, αVβ8 at 1.2nM, and α5β1 at 7.7nM[1, 2]. GLPG0187 possesses anti-tumor activity, blocking the αvβ6 integrin receptor on cancer cells, locally preventing TGF-β activation, thereby reducing TGF-β signaling and immune evasion in cancer cells[3].
In vitro, GLPG0187 (20nM, 100nM, 200nM, 1µM) pretreatment of human small airway epithelial cells (HSAE) for 2h blocked SARS-CoV-2 delta and Omicron pseudovirus infection of airway epithelial cells in a dose-dependent manner[4]. Treatment of TALL-104 T lymphoblast cells with GLPG0187 (4µM) for 24h significantly enhanced the killing effect of TALL-104 T lymphoblast cells on HCT116 p53-null cells[5].
In vivo, GLPG0187 (100mg/kg) administered via intraperitoneal injection for 17 days in a mouse model of prostate cancer bone metastasis significantly reduced the number of tumor cells in the implanted metatarsal bones of the mice, significantly increased the number of osteoblasts, and significantly decreased microvessel density[6].
References:
[1] van der Horst G, van den Hoogen C, Buijs J T, et al. Targeting of αv-integrins in stem/progenitor cells and supportive microenvironment impairs bone metastasis in human prostate cancer[J]. Neoplasia, 2011, 13(6): 516-IN9.
[2] Zhao-He L I, You Z, You-Xiang D, et al. Roles of integrin in tumor development and the target inhibitors[J]. Chinese journal of natural medicines, 2019, 17(4): 241-251.
[3] MacDonald W J, Verschleiser B, Carlsen L, et al. Broad spectrum integrin inhibitor GLPG-0187 bypasses immune evasion in colorectal cancer by TGF-β signaling mediated downregulation of PD-L1[J]. American Journal of Cancer Research, 2023, 13(7): 2938.
[4] Huntington K E, Carlsen L, So E Y, et al. Integrin/TGF-β1 inhibitor GLPG-0187 blocks SARS-CoV-2 delta and omicron pseudovirus infection of airway epithelial cells in vitro, which could attenuate disease severity[J]. Pharmaceuticals, 2022, 15(5): 618.
[5] Verschleiser B, MacDonald W, Carlsen L, et al. Pan-integrin inhibitor GLPG-0187 promotes T-cell killing of mismatch repair-deficient colorectal cancer cells by suppression of SMAD/TGF-β signaling[J]. American Journal of Cancer Research, 2023, 13(7): 2878.
[6] Reeves K J, Hurrell J E, Cecchini M, et al. Prostate cancer cells home to bone using a novel in vivo model: modulation by the integrin antagonist GLPG0187[J]. International journal of cancer, 2015, 136(7): 1731-1740.
GLPG0187是一种广谱整合素（integrin）受体拮抗剂，对多种整合素受体表现出选择性，其IC50值如下：αVβ1为1.3nM，αVβ3为3.7nM，αVβ5为2.0nM，αVβ6为1.4nM，αVβ8为1.2nM，α5β1为7.7nM[1, 2]。GLPG0187具有抗肿瘤活性，能够阻断癌细胞上的αvβ6整合素受体，局部阻止TGF-β的激活，从而减少癌细胞的TGF-β信号和免疫逃逸[3]。
在体外，GLPG0187（20nM, 100nM, 200nM, 1µM）预处理人小气道上皮细胞（HSAE）2h，以剂量依赖性方式阻断了SARS-CoV-2 delta和Omicron假病毒感染气道上皮细胞[4]。GLPG0187（4µM）处理TALL-104 T淋巴母细胞24h，显著促进了TALL-104 T淋巴母细胞对HCT116 p53-null细胞的杀伤作用[5]。
在体内，GLPG0187（100mg/kg）通过腹腔注射治疗前列腺癌骨转移模型小鼠17天，显著减少了小鼠体内植入的跖骨中肿瘤细胞的数量，显著增加了成骨细胞数量，显著降低了微血管密度[6]。