GLPG-0187

GLPG-0187 (GLPG0187) is a highly potent, broad spectrum integrin receptor antagonist with IC50 of 1-10 nM for αvβ1, αvβ3, αvβ5, αvβ6, αvβ8 and α5β1; significantly inhibits angiogenesis both in vivo and in vitro, osteoclastogenesis in vitro, and bone loss in vivo; inhibits de novo formation and progression of bone and visceral metastases in prostate cancer and breast cancer mice models.Solid Tumors Phase 1 Clinical (In Vitro) :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. 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. (In Vivo) :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.