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The goal of this study was to design, experimentally validate, and apply a virtual screening workflow to identify novel hERG channel blockers. The hERG channel is an important antitarget in drug development since cardiotoxic risks remain as a major cause of attrition. A ligand-based pharmacophore model collection was developed and theoretically validated. The seven most complementary and suitable models were used for virtual screening of in-house and commercially available compound libraries. From the hit lists, 50 compounds were selected for experimental validation through bioactivity assessment using patch clamp techniques. Twenty compounds inhibited hERG channels expressed in HEK 293 cells with IC50 values ranging from 0.13 to 2.77 μM, attesting to the suitability of the models as cardiotoxicity prediction tools in a preclinical stage.

We performed a single-day cross-sectional study to assess the prevalence of vitamin D deficiency as well as folate status in healthy young female volunteers well educated with respect to health information.We assessed dietary intake of vitamin D and calcium, serum concentrations of 25-OH-vitamin D(3), folate, red blood cell folate and other dietary, laboratory, and lifestyle parameters in 215 young healthy women (age 18-30 years) on a single day at the end of the winter months. Primary aim was to investigate the prevalence of hypovitaminosis D. Folic acid status was a secondary study aim.Mean daily ingestion of vitamin D was 2.25 μg/day with a daily calcium intake of 749 mg/day. 6.9% had hypovitaminosis D (25-OH-vitamin D(3)30 nmol/L) and 89.3% were vitamin D insufficient (75 nmol/L). Preplanned subpopulation comparison (lower vs. upper quartile) revealed a significant negative correlation (P = 0.048) between plasma PTH and 25-OH-vitamin D(3) levels. Fifteen individuals (6.9%) were folic acid deficient (140 ng/mL RBC folate). Only 9.3% reached RBC folate concentrations regarded as optimal for the prevention of fetal neural tube defects (400 ng/mL).The prevalence of hypovitaminosis D in healthy young women trained in health care professions is low but 89.3% can be classified as vitamin D insufficient in spring. Folate status can also be considered not sufficient. Considering the emerging role of higher vitamin D plasma levels for many health conditions, a timely correction of vitamin D status in the general Austrian population appears appropriate.