 Chemical Structure.png)
Tecalcet (KRN-568; NPS-R-568; R-568) is a novel, potent, orally bioactive calcimimetic compound/calcium channel agonist that can be potentially used for the treatment of hyperparathyroidism, postmenopausal symptom. It stimulates the calcium-sensing receptor (CaSR) allosterically and favorably. In rats with severe secondary hyperparathyroidism, NPS R-568 prevents parathyroid hyperplasia. In rats suffering from mild to severe secondary hyperparathyroidism due to diet or renal disease, NPS R-568 reduces plasma PTH. In uremic rats, osteitis fibrosa is stopped or reversed by NPS R-568.
Physicochemical Properties
| Molecular Formula | C18H23CL2NO |
| Molecular Weight | 340.287323236465 |
| Exact Mass | 339.116 |
| Elemental Analysis | C, 63.53; H, 6.81; Cl, 20.84; N, 4.12; O, 4.70 |
| CAS # | 177172-49-5 |
| Related CAS # | 148717-54-8; 177172-49-5 (HCl) |
| PubChem CID | 158796 |
| Appearance | White to off-white solid powder |
| Boiling Point | 416.3ºC at 760 mmHg |
| Flash Point | 205.6ºC |
| Vapour Pressure | 3.86E-07mmHg at 25°C |
| LogP | 5.824 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 2 |
| Rotatable Bond Count | 7 |
| Heavy Atom Count | 22 |
| Complexity | 286 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | C[C@](C1C=C(OC)C=CC=1)(NCCCC1C(Cl)=CC=CC=1)[H].[H]Cl |
| InChi Key | YJXUXANREVNZLH-PFEQFJNWSA-N |
| InChi Code | InChI=1S/C18H22ClNO.ClH/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;1H/t14-;/m1./s1 |
| Chemical Name | 3-(2-chlorophenyl)-N-[(1R)-1-(3-methoxyphenyl)ethyl]propan-1-amine;hydrochloride |
| Synonyms | Tecalcet HCl; KRN-568; NPS-R-568; R-568; KRN568; NPS-R568; R568; Tecalcet hydrochloride; Norcalcin |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | Tecalcet (NPS 568, 0.1–100 μM) increases [Ca2+]i in a stereoselective and concentration-dependent way[3]. Tecalcet (NPS 568, 0.1-100 nM) lowers the EC50 value for extracellular Ca21 to 0.61±0.04 mM by moving the concentration-response curve for extracellular Ca2+ to the left without affecting the maximal response[3]. |
| ln Vivo | Tecalcet (1.5 and 15 mg/kg, orally, twice daily for 4 days) inhibits the proliferation of PT cells in rats with renal insufficiency[1]. |
| Animal Protocol |
10-wk-old Male Sprague-Dawley rats weighing 310-350 g 1.5 and 15 mg/kg Orally twice daily for 4 days |
| References |
[1]. The calcimimetic compound NPS R-568 suppresses parathyroid cell proliferation in rats with renal insufficiency. Control of parathyroid cell growth via a calcium receptor. Journal of Clinical Investigation 100(12), 2977-2983 (1997). [2]. The parathyroid calcium receptor: a novel therapeutic target for treating hyperparathyroidism. Pediatr.Nephrol. 10(3), 275-279 (1996). [3]. Calcimimetics with potent and selective activity on the parathyroid calcium receptor. Proceedings of the National Academy of Sciences of the United States of America 95(7), 4040-4045 (1998). |
Solubility Data
| Solubility (In Vitro) | DMSO: ~50 mg/mL (~146.9 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.35 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (7.35 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 3: 2.5 mg/mL (7.35 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9387 mL | 14.6933 mL | 29.3867 mL | |
| 5 mM | 0.5877 mL | 2.9387 mL | 5.8773 mL | |
| 10 mM | 0.2939 mL | 1.4693 mL | 2.9387 mL |