GLPG0187, a broad spectrum integrin receptor antagonist, inhibits αvβ1-integrin (IC50: 1.3 nM).

αvβ1:1.3 nM

GLPG0187是一种有效地抑制骨质破坏和血管生成的抑制剂。在固相测定中，GLPG0187针对数个RGD整合素受体显示出选择性(IC50s：1.3/3.7/2.0/1.4/1.2/7.7 nM, 对αvβ1/3/5/6/8及α5β1)。GLPG0187剂量依赖性地提高E-钙黏蛋白/波形蛋白比率。GLPG0187剂量依赖性地降低前列腺癌细胞中高含量醛脱氢酶亚群的大小。GLPG0187导致细胞圆化和聚集。GLPG0187剂量依赖性地并显著降低肿瘤细胞迁移。在所有浓度下，GLPG0187显著减少细胞增殖。

GLPG0187通过阻断αv-integrins显著减少了转移性肿瘤生长。GLPG0187明显降低骨肿瘤负担并显著抑制每只小鼠骨转移数量。在治疗期间，GLPG0187显著抑制了骨转移的进展和新骨转移的形成。

HSP90 competition isothermal calorimetry: Kd values for AT13387 binding to HSP90 are determined with a competition Isothermal Calorimetry (ITC) format. ITC experiments are performed on a Micro Cal VP-ITC at 25 °C in a buffer comprising 25 mM Tris, 100 mM NaCl, 1 mM MgCl2 and 1 mM Tris(2-carboxy- ethyl)phosphine at pH 7.4 in order to maintain the higher affinit

Tumour cell proliferation is determined using the MTS assay. PC3 cells are seeded at 10,000 cells/well in 96 well plates containing either GLPG0187 (0.5, 5, or 50 ng/mL), vehicle or media control, then cultured in 100 μL medium for 24 hr. Cell proliferation is analyzed using 20 μL MTS dye incubated for 3 hr at 37°C in the dark. Absorbance from each well (6/treatment) is quantified at 490 nm and the mean fluorescence calculated. The assay is repeated at 48, 72 and 96 hr, on three independent occasions.

GLPG0187 is prepared in 1:1 dimethyl sulfoxide in PBS.The effect of GLPG0187 on bone loss is evaluated in 3-month-old castrated male mice after 4 weeks of treatment with dosing starting immediately after castration (preventive protocol). Two different modes of administration are used: either subcutaneous twice daily with 10, 30, or 100 mg/kg of GLPG0187, either oral, twice daily with 30, 100, or 300 mg/kg of GLPG0187.