GLPG0187
(Synonyms: GLPG0187,一种广谱的INTEGRIN受体拮抗剂,具有抗肿瘤活性) 目录号 : GC19167
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。
Cas No.:1320346-97-1
Sample solution is provided at 25 µL, 10mM.
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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]。
| Cell experiment [1]: | |
Cell lines | Human small airway epithelial (HSAE) |
Preparation Method | HSAE cells were pre-treated with 20nM, 100nM, 200nM, or 1µM GLPG0187 for 2h followed by spin infection with either a pseudovirus expressing the D614G spike protein variant or a VsVg positive control for 24h. |
Reaction Conditions | 20nM, 100nM, 200nM, 1µM; 2h |
Applications | Pre-treatment with GLPG0187 resulted in the most significant decrease in pseudovirus infection by the Delta variant. |
| Animal experiment [2]: | |
Animal models | Server combined immune-deficiency (SCID) mouse |
Preparation Method | A single murine metatarsal was engrafted into a dorsal skinfold chamber implanted on a SCID mouse. Fluorescently-labeled human prostate (PC3-GFP) cancer cells were administered via intracardiac (i.c) injection. Animals were administered GLPG0187 daily for 17 days (i.p 100mg/kg; n=20, dissolved in 2% DMSO in PBS) or vehicle control (2% DMSO in PBS n=20), commencing on the same day as tumour cell injection (day 7). Metatarsal recordings were taken every 48h for up to 4 weeks. At the end of treatment animals were culled (day 25). Tissue was harvested and processed for microCT, multiphoton analysis, histology and immunohistochemistry. |
Dosage form | 100mg/kg; 17 days; i.p. |
Applications | GLPG0187 significantly reduced the number of tumour cells present in the implanted metatarsal from day 17 onwards. The number of osteoblasts was significantly increased in mice treated with GLPG0187. The microvessel density in the GLPG0187 treatment group was significantly lower compared to the control group. |
References: | |
| Cas No. | 1320346-97-1 | SDF | |
| 别名 | GLPG0187,一种广谱的INTEGRIN受体拮抗剂,具有抗肿瘤活性 | ||
| Canonical SMILES | O=C(O)[C@H](CNC1=NC(C)=NC(N2CCC(C3=NC4=C(CCCN4)C=C3)CC2)=C1C)NS(=O)(C5=CC=C(OC)C=C5)=O | ||
| 分子式 | C29H37N7O5S | 分子量 | 595.71 |
| 溶解度 | DMSO : 15 mg/mL (25.18 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.6787 mL | 8.3933 mL | 16.7867 mL |
| 5 mM | 335.7 μL | 1.6787 mL | 3.3573 mL |
| 10 mM | 167.9 μL | 839.3 μL | 1.6787 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
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- Purity: >98.50%
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