GLPG0187, 一种广谱的INTEGRIN受体拮抗剂,具有抗肿瘤活性

IC50: 1.3 nM (α _v β ₁ )

In a solid-phase assay, GLPG0187 shows selectivity for several RGD integrin receptors with IC ₅₀ s of 1.3, 3.7, 2.0, 1.4, 1.2, 7.7 nM for α _v β ₁ , α _v β ₃ , α _v β ₅ , α _v β ₆ ,α _v β ₈ , and α ₅ β ₁ . GLPG0187 is a potent inhibitor of osteoclastic bone resorption and angiogenesis. Treatment with GLPG0187 dose-dependently increases the E-cadherin/vimentin ratio, rendering the cells a more epithelial, sessile phenotype. GLPG0187 dose-dependently diminishes the size of the aldehyde dehydrogenase high subpopulation of prostate cancer cells. GLPG0187 treatment results in cell rounding and clumping. GLPG0187 demonstrates a dose-dependent significant reduction in tumour cell migration. GLPG0187 at all concentrations significantly reduces cell proliferation.

Blocking α _v -integrins by GLPG0187 markedly reduces their metastatic tumor growth. Bone tumor burden is significantly lower and the number of bone metastases/mouse is significantly inhibited. The progression of bone metastases and the formation of new bone metastases during the treatment period is significantly inhibited.