VS-105: a novel vitamin D receptor modulator with cardiovascular protective effects.

摘要: BACKGROUND AND PURPOSE Vitamin D receptor (VDR) modulators (VDRMs) such as calcitriol, paricalcitol and doxercalciferol are commonly used to manage hyperparathyroidism secondary chronic kidney disease (CKD). CKD patients experience extremely high risks of cardiovascular morbidity mortality. Clinical observations show that VDRM therapy may be associated with cardio-renal protective survival benefits for patients. However, hypercalcaemia remains a serious side effect current VDRMs, which leads the need frequent dose titration serum Ca (calcium) monitoring. Significant clinical can derived from effects without hypercalcaemic liability. EXPERIMENTAL APPROACH Male Sprague–Dawley rats were 5/6 nephrectomized 6 weeks later, after they had established uraemia, elevated parathyroid hormone levels, endothelial dysfunction left ventricular hypertrophy, treated VS-105, novel VDRM. The VS-105 also tested in cultured HL-60 cells. KEY RESULTS induced cell differentiation an EC50 value at 11.8 nM. Treatment (i.p., 3× week over period 2 weeks) by (0.004–0.64 µg·kg−1) effectively suppressed raising or phosphate levels. Furthermore, treatment improved endothelium-dependent aortic relaxation attenuated abnormalities range did not affect Similar results obtained when was administered i.p. oral gavage. CONCLUSIONS IMPLICATIONS exhibits overall therapeutic product profile supports expanded use realize VDR activation.