Synthesis of VS-105: A novel and potent vitamin D receptor agonist with reduced hypercalcemic effects

Chen, Barbara; Kawai, Megumi; Wu-Wong, J. Ruth

doi:10.1016/j.bmcl.2013.08.076

Cited by 12 publications

(6 citation statements)

References 31 publications

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“…The synthesis scheme of VS-105 was published previously. 22 All other reagents used were of analytical grade.…”

Section: Methodsmentioning

confidence: 99%

A Novel Vitamin D Receptor Agonist, VS-105, Improves Bone Mineral Density without Affecting Serum Calcium in a Postmenopausal Osteoporosis Rat Model

Wu-Wong¹,

Wessale²,

Chen³

et al. 2020

Journal of Exploratory Research in Pharmacology

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Background and objectives: VS-105, a novel vitamin D receptor agonist with significantly less hypercalcemic side effects than calcitriol, is a useful tool to investigate whether or not a vitamin D receptor agonist at non-hypercalcemic doses could improve bone mineral density (BMD). Methods: VS-105 and calcitriol were evaluated in an ovariectomized (OVX) osteoporosis rat model and in calvariae bone organ culture. Results: Treatment of OVX rats by VS-105 (0.1, 0.2 or 0.5 µg/kg, intraperitoneal, 3×/week, for 90 days) significantly improved BMD in the L3 lumbar vertebra in a dose-dependent manner (sham vs. OVX/vehicle: 324 ± 14 vs. 279 ± 10 mg/cm 2 ; VS-105 at 0.1, 0.2 and 0.5 µg/kg: 306 ± 9, 329 ± 12, and 327 ± 10 mg/cm 2 , respectively) without affecting serum calcium (Ca). Calcitriol at 0.1 µg/kg significantly increased BMD but it also increased serum Ca. VS-105 and calcitriol at the test doses significantly suppressed serum parathyroid hormone and promoted tibia bone growth. With respect to biomarkers of bone remodeling, calcitriol and VS-105 both significantly elevated serum osteocalcin. In the calvariae bone organ culture, net Ca release was significantly less in VS-105-treated groups (vs. calcitriol). Conclusions: VS-105 is efficacious in improving BMD in a dose range that does not affect serum Ca in OVX rats; the improvement in BMD by VS-105 is attributable to increased osteoblastic activity and reduced osteoclastic bone resorption.

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“…The synthesis scheme of VS-105 was published previously. 22 All other reagents used were of analytical grade.…”

Section: Methodsmentioning

confidence: 99%

A Novel Vitamin D Receptor Agonist, VS-105, Improves Bone Mineral Density without Affecting Serum Calcium in a Postmenopausal Osteoporosis Rat Model

Wu-Wong¹,

Wessale²,

Chen³

et al. 2020

Journal of Exploratory Research in Pharmacology

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“…21 However, the same authors, using the same method reported EC 50 of calcitriol to be 15 nM. 22 Collectively, there is a substantial variability between EC 50 values obtained by various methods.…”

Section: ■ Author Informationmentioning

confidence: 98%

Profiling of Vitamin D Metabolic Intermediates toward VDR Using Novel Stable Gene Reporter Cell Lines IZ-VDRE and IZ-CYP24

Bartoňková

Grycová

Dvořák

2016

Chem. Res. Toxicol.

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The role of vitamin D receptor (VDR) in immune responses has been broadly studied and it has been shown that activated VDR alters the levels of some interleukins (ILs). In this study, we studied the opposite, i.e. whether 13 selected pro-inflammatory and anti-inflammatory ILs influence the transcriptional activity of human VDR. The experimental models of choice were two human stably transfected gene reporter cell lines IZ-VDRE and IZ-CYP24, which were designed to evaluate the transcriptional activity of VDR. The gene reporter assays revealed inhibition of calcitriol-induced luciferase activity by IL-4 and IL-13, when 1 ng/mL of these two compounds decreased the effect of calcitriol down to 60% of the control value. Consistently, calcitriol-induced expression of CYP24A1 mRNA was also significantly decreased by IL-4 and IL-13. The expression of VDR and CYP27B1 mRNAs was not influenced by any of the 13 tested ILs. These data suggest possible cross-talk between the VDR signalling pathway and IL-4-and IL-13-mediated cell signalling.

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“…Figure 21 (2012-2013) [298][299][300][301][302][303][304][305][306][307][308][309][310][311][312][313]. 24S-Methyl-21-epi-2-methylene-22-oxa-1α,25-dihydroxyvitamin D 3 (1191, VS-105) [306] bound to VDR is highly inductive of functional responses in vitro and effectively suppresses PTH in a dose range that does not affect serum calcium in 5/6 NX uremic rats.…”

Section: Resultsmentioning

confidence: 99%

The Centennial Collection of VDR Ligands: Metabolites, Analogs, Hybrids and Non-Secosteroidal Ligands

Maestro

Seoane

2022

Nutrients

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Synthesis of VS-105: A novel and potent vitamin D receptor agonist with reduced hypercalcemic effects

Cited by 12 publications

References 31 publications

A Novel Vitamin D Receptor Agonist, VS-105, Improves Bone Mineral Density without Affecting Serum Calcium in a Postmenopausal Osteoporosis Rat Model

A Novel Vitamin D Receptor Agonist, VS-105, Improves Bone Mineral Density without Affecting Serum Calcium in a Postmenopausal Osteoporosis Rat Model

Profiling of Vitamin D Metabolic Intermediates toward VDR Using Novel Stable Gene Reporter Cell Lines IZ-VDRE and IZ-CYP24

The Centennial Collection of VDR Ligands: Metabolites, Analogs, Hybrids and Non-Secosteroidal Ligands

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