GLPG0187

GLPG0187 is a broad spectrum integrin receptor antagonist with antitumor activity; inhibits αvβ1-integrin with an IC50 of 1.3 nM.

In a solid-phase assay, GLPG0187 shows selectivity for several RGD integrin receptors with IC50s of 1.3, 3.7, 2.0, 1.4, 1.2, 7.7 nM for αvβ1, αvβ3, αvβ5, αvβ6,αvβ8, and α5β1. 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[1]. 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[2].

Blocking αv-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[1].

References:
[1]. van der Horst G, et al. Targeting of α(v)-integrins in stem/progenitor cells and supportive microenvironment impairs bone metastasis in human prostate cancer. Neoplasia. 2011 Jun;13(6):516-25.
[2]. Reeves KJ, et al. Prostate cancer cells home to bone using a novel in vivo model: modulation by the integrin antagonist GLPG0187. Int J Cancer. 2015 Apr 1;136(7):1731-40.