| Stereochemistry | ABSOLUTE |
| Molecular Formula | C18H22ClNO |
| Molecular Weight | 303.826 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
COC1=CC(=CC=C1)[C@@H](C)NCCCC2=CC=CC=C2Cl
InChI
InChIKey=ZVQUCWXZCKWZBP-CQSZACIVSA-N
InChI=1S/C18H22ClNO/c1-14(16-8-5-10-17(13-16)21-2)20-12-6-9-15-7-3-4-11-18(15)19/h3-5,7-8,10-11,13-14,20H,6,9,12H2,1-2H3/t14-/m1/s1
| Molecular Formula | C18H22ClNO |
| Molecular Weight | 303.826 |
| Charge | 0 |
| Count |
MOL RATIO
1 MOL RATIO (average) |
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
Tecalcet (also known as KRN-568; NPS-R-568; R-568), is an oral calcium channel agonist potentially for the treatment of hyperparathyroidism. Calcimimetics, such as Tecalcet, are agonists and activate the calcium channel in a non-competitive fashion. Tecalcet does not compete directly with calcium that activates the receptor through binding in the extracellular domain of these receptors, but rather, calcimimetics such as Tecalcet, bind allosterically in the seven transmembranes to ‘sensitize’ the receptor to extracellular calcium. Tecalcet acts as an agonist of the calcium receptors of the parathyroid cells, causing a decrease in PTH release. Tecalcet also acts on the parafollicular cells (C-cells) of the thyroid gland, resulting in an increase in calcitonin release. These effects ultimately lead to a decrease in plasma calcium concentrations. Studies in rats have shown that oral administration of R-568 at doses ranging from 3 to 100 mg/kg caused a rapid (<30 minutes) decrease in plasma PTH concentrations and an increase in calcitonin concentrations, accompanied by a dose-dependent decrease in calcium concentrations. Tecalcet had been in phase II clinical trials by for the treatment of hyperparathyroidism, postmenopausal osteoporosis and rheumatic disorders in Japan and US. Development of Tecalcet has been discontinued.
Originator
Approval Year
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
Drug as victim
Sourcing
PubMed
Patents
Sample Use Guides
Ovine AFMSCs were seeded at a density of 3000 cells/cm^2 in 6 well plates and treated for 14 days in the presence of increasing concentrations of calcimimetics R-568 and S-568 (0.1–10 mkM). In some experiments, the inhibitor Calhex-231 was pre-incubated 30 minutes before the addition of calcimimetics. To test the appropriate concentration of calcimimetics, MTT, cell number, Alkaline Phosphatase (ALP) and Alizarin Red S (ARS) assays were performed. The effect of calcimimetics on oAFMSC viability was assessed by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) method. After treatment with calcimimetics as described above, a solution of MTT in phosphate buffered saline (PBS) was added to each well to a final concentration of 0.5 mg/ml. After a further 3 hours’ incubation the cells were washed and 200 mkl DMSO was added for crystal solubilization. The plates were put in the dark at 37C, and continuous gentle shaking was performed for 30 min to thoroughly dissolve the MTT dye. The spectrometric absorbance at 540 nm (for formazan dye) and 690 nm (as a background level) was read using a microplate reader
