product name Cinacalcet HCl
Description: Cinacalcet HCl (also known as AMG-073 HCl) is a new class of compounds for the treatment of hyperparathyroidism. Cinacalcet is a type II calcimimetic agent which controls calcium levels in cells by allosteric activation of CaSR. In the presence of calcium ions, it can inhibit parathyroid hormone secretion by activating CaSR in parathyroid glands. Cinacalcet has been used clinically to treat secondary hyperparathyroidism due to end-stage renal disease or hypercalcemia in patients with parathyroid carcinoma.
References: Kidney Int Suppl. 2003 Jun;(85):S91-6; Clin Ther. 2005 Nov;27(11):1725-51.
393.87
Formula
C22H22F3N.HCl
CAS No.
364782-34-3
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 79 mg/mL (200.6 mM)
Water: <1 mg/mL
Ethanol: 33 mg/mL (83.8 mM)
Solubility (In vivo)
30% PEG400+0.5% Tween80+5% Propylene glycol: 30mg/mL
Synonyms
AMG-073 HCl
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19405032
| In Vitro |
In vitro activity: AMG-073 represents a new class of compounds for the treatment of hyperparathyroidism known as calcimimetics, which reduce parathyroid hormone (PTH) synthesis and secretion by increasing the sensitivity of the parathyroid calcium-sensing receptor (CaR) to extracellular calcium. AMG-073 has potential advantages as a therapy for secondary hyperparathyroidism because it mimics the effects of extracellular calcium to suppress PTH secretion, even in the presence of hyperphosphatemia, without the risk of causing hypercalcemia and/or hyperphosphatemia. AMG-073 produces a concentration-dependent increase in cytoplasmic calcium in human embryonic kidney cells expressing the CaSR. In bovine parathyroid cells and a buffer containing calcium 0.5 mM, AMG 073 (3 nM – 1 μM) produces a concentration-dependent decrease in PTH levels with IC50 of 27 nM. Kinase Assay: Cell Assay: |
|---|---|
| In Vivo | AMG-073 orally administrated to normal rats at dose of 1, 3, 10, and 30 mg/kg in 20% sulfobutyl ether β-cyclodextrin sodium produces a significant dose-dependent reduction in PTH levels for 1 to 4 hours after administration. At 8 hours, the 10- and 30-mg/kg doses of AMG-073 produces significant reductions in PTH levels compared with controls that disappears by 24 hours. Significant dose-dependent reduction in serum calcium levels are observed at 4, 8, and 24 hours after oral administration of AMG-073 3, 10, and 30 mg/kg, respectively. A transient reduction in serum phosphorus levels is observed only with the highest dose of AMG-073. In addition, increased calcitonin levels that paralleled PTH suppression are observed with AMG-073 40 mg/kg in rats. As in normal rats, a rapid dose-dependent reduction in PTH and calcium levels is observed in 5 of 6 nephrectomized rats after oral administration of AMG-073. In addition, oral AMG-073 at 5 and 10 mg/kg for 4 weeks significantly reduces parathyroid weight compared with controls. |
| Animal model | |
| Formulation & Dosage | |
| References | Kidney Int Suppl. 2003 Jun;(85):S91-6; Clin Ther. 2005 Nov;27(11):1725-51. |
Related Posts
product name Cinacalcet HCl
Description: NPS-2143, also known as SB-262470 and SB-262470A, is a novel, potent and selective antagonist of Ca(2+) receptor with IC50 of 43 nM. NPS-2143 stimulates release of parathyroid hormone. Calcilytic drugs have been researched as potential treatments for osteoporosis, and as the first such compound developed, NPS-2143 is still widely used in research into the CaSR receptor as well as design of newer calcilytic agents.
References: J Pharmacol Exp Ther. 2001 Oct;299(1):323-31; J Endocrinol. 2006 Oct;191(1):189-95.
408.92
Formula
C24H25ClN2O2
CAS No.
284035-33-2
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 82 mg/mL (200.5 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
2% DMSO+Corn oil: 10mg/mL
Synonyms
SB262470
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19405041
| In Vitro |
In vitro activity: NPS 2143 blocks increases in cytoplasmic Ca2+ concentrations with IC50 of 43 nM elicited by activating the Ca2+ receptor in HEK 293 cells expressing the human Ca2+ receptor. NPS 2143 stimulates parathyroid hormone (PTH) secretion from bovine parathyroid cells with EC50 of 41 nM. Moreover, NPS 214 also blocks the inhibitory effects of calcimimetic NPS R-467 on PTH secretion from bovine parathyroid cells and the inhibitory effects of extracellular Ca2+ on isoproterenol-stimulated increases in cyclic AMP formation. In HEK-293 cells transiently expressing hCaSRs, NPS 2143 significantly suppresses the kokumi taste by effectively inhibiting the activity of both GSH (data not shown) and γ-Glu-Val-Gly. A recent study shows that NPS 2143 treatment suppresses low molecular weight fractions of azuki hydrolysate-induced cholecystokinin (CCK) secretion in CaSR-transfected HEK 293 cells. Kinase Assay: Cell Assay: Calcilytics NPS-2143 has been reported to diminish the sensitivity of the CaSR for [Ca2+]o, resulting in an attenuated signal transduction in vitro and increased secretion of PTH in vivo. In addition, The EC50 values of NPS-2143 are 4.27, 1.56, 1.61, 2.46, 2.07 and 3.15mM for the wild-type CaSR, mutant CaSR (T151R, P221L, E767Q, G830S, and A844T), respectively. Apart from these, in HEK 293T cells expressing CaSR, NPS-2143 has been revealed to inhibit the [Ca2+]o-induced cytosolic calcium signal in a concentration-dependent manner. |
|---|---|
| In Vivo | In rats, NPS 2143 results in a rapid 4- to 5-fold increase in plasma PTH levels and also a transient increase in plasma Ca2+ levels. In normotensive rats, NPS 2143 administration (1 mg/kg) by i.v. markedly increases mean arterial blood pressure (MAP) in the presence of parathyroid glands. |
| Animal model | Chronic indwelling catheters are implanted in the inferior vena cava and in the abdominal aorta of male Sprague-Dawley rats. |
| Formulation & Dosage | Dissolved in 20% aqueous solution of 2-hydroxypropyl-β-cyclodextrin; ≤0.1 μmol/kg · min; i.v. administration |
| References | J Pharmacol Exp Ther. 2001 Oct;299(1):323-31; J Endocrinol. 2006 Oct;191(1):189-95. |
Related Posts
product name Cinacalcet HCl
Description: Cinacalcet HCl (also known as AMG-073 HCl) is a new class of compounds for the treatment of hyperparathyroidism. Cinacalcet is a type II calcimimetic agent which controls calcium levels in cells by allosteric activation of CaSR. In the presence of calcium ions, it can inhibit parathyroid hormone secretion by activating CaSR in parathyroid glands. Cinacalcet has been used clinically to treat secondary hyperparathyroidism due to end-stage renal disease or hypercalcemia in patients with parathyroid carcinoma.
References: Kidney Int Suppl. 2003 Jun;(85):S91-6; Clin Ther. 2005 Nov;27(11):1725-51.
393.87
Formula
C22H22F3N.HCl
CAS No.
364782-34-3
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 79 mg/mL (200.6 mM)
Water: <1 mg/mL
Ethanol: 33 mg/mL (83.8 mM)
Solubility (In vivo)
30% PEG400+0.5% Tween80+5% Propylene glycol: 30mg/mL
Synonyms
AMG-073 HCl
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19405032
| In Vitro |
In vitro activity: AMG-073 represents a new class of compounds for the treatment of hyperparathyroidism known as calcimimetics, which reduce parathyroid hormone (PTH) synthesis and secretion by increasing the sensitivity of the parathyroid calcium-sensing receptor (CaR) to extracellular calcium. AMG-073 has potential advantages as a therapy for secondary hyperparathyroidism because it mimics the effects of extracellular calcium to suppress PTH secretion, even in the presence of hyperphosphatemia, without the risk of causing hypercalcemia and/or hyperphosphatemia. AMG-073 produces a concentration-dependent increase in cytoplasmic calcium in human embryonic kidney cells expressing the CaSR. In bovine parathyroid cells and a buffer containing calcium 0.5 mM, AMG 073 (3 nM – 1 μM) produces a concentration-dependent decrease in PTH levels with IC50 of 27 nM. Kinase Assay: Cell Assay: |
|---|---|
| In Vivo | AMG-073 orally administrated to normal rats at dose of 1, 3, 10, and 30 mg/kg in 20% sulfobutyl ether β-cyclodextrin sodium produces a significant dose-dependent reduction in PTH levels for 1 to 4 hours after administration. At 8 hours, the 10- and 30-mg/kg doses of AMG-073 produces significant reductions in PTH levels compared with controls that disappears by 24 hours. Significant dose-dependent reduction in serum calcium levels are observed at 4, 8, and 24 hours after oral administration of AMG-073 3, 10, and 30 mg/kg, respectively. A transient reduction in serum phosphorus levels is observed only with the highest dose of AMG-073. In addition, increased calcitonin levels that paralleled PTH suppression are observed with AMG-073 40 mg/kg in rats. As in normal rats, a rapid dose-dependent reduction in PTH and calcium levels is observed in 5 of 6 nephrectomized rats after oral administration of AMG-073. In addition, oral AMG-073 at 5 and 10 mg/kg for 4 weeks significantly reduces parathyroid weight compared with controls. |
| Animal model | |
| Formulation & Dosage | |
| References | Kidney Int Suppl. 2003 Jun;(85):S91-6; Clin Ther. 2005 Nov;27(11):1725-51. |
Related Posts
product name Cinacalcet HCl
Description: NPS-2143, also known as SB-262470 and SB-262470A, is a novel, potent and selective antagonist of Ca(2+) receptor with IC50 of 43 nM. NPS-2143 stimulates release of parathyroid hormone. Calcilytic drugs have been researched as potential treatments for osteoporosis, and as the first such compound developed, NPS-2143 is still widely used in research into the CaSR receptor as well as design of newer calcilytic agents.
References: J Pharmacol Exp Ther. 2001 Oct;299(1):323-31; J Endocrinol. 2006 Oct;191(1):189-95.
408.92
Formula
C24H25ClN2O2
CAS No.
284035-33-2
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 82 mg/mL (200.5 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
2% DMSO+Corn oil: 10mg/mL
Synonyms
SB262470
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19405041
| In Vitro |
In vitro activity: NPS 2143 blocks increases in cytoplasmic Ca2+ concentrations with IC50 of 43 nM elicited by activating the Ca2+ receptor in HEK 293 cells expressing the human Ca2+ receptor. NPS 2143 stimulates parathyroid hormone (PTH) secretion from bovine parathyroid cells with EC50 of 41 nM. Moreover, NPS 214 also blocks the inhibitory effects of calcimimetic NPS R-467 on PTH secretion from bovine parathyroid cells and the inhibitory effects of extracellular Ca2+ on isoproterenol-stimulated increases in cyclic AMP formation. In HEK-293 cells transiently expressing hCaSRs, NPS 2143 significantly suppresses the kokumi taste by effectively inhibiting the activity of both GSH (data not shown) and γ-Glu-Val-Gly. A recent study shows that NPS 2143 treatment suppresses low molecular weight fractions of azuki hydrolysate-induced cholecystokinin (CCK) secretion in CaSR-transfected HEK 293 cells. Kinase Assay: Cell Assay: Calcilytics NPS-2143 has been reported to diminish the sensitivity of the CaSR for [Ca2+]o, resulting in an attenuated signal transduction in vitro and increased secretion of PTH in vivo. In addition, The EC50 values of NPS-2143 are 4.27, 1.56, 1.61, 2.46, 2.07 and 3.15mM for the wild-type CaSR, mutant CaSR (T151R, P221L, E767Q, G830S, and A844T), respectively. Apart from these, in HEK 293T cells expressing CaSR, NPS-2143 has been revealed to inhibit the [Ca2+]o-induced cytosolic calcium signal in a concentration-dependent manner. |
|---|---|
| In Vivo | In rats, NPS 2143 results in a rapid 4- to 5-fold increase in plasma PTH levels and also a transient increase in plasma Ca2+ levels. In normotensive rats, NPS 2143 administration (1 mg/kg) by i.v. markedly increases mean arterial blood pressure (MAP) in the presence of parathyroid glands. |
| Animal model | Chronic indwelling catheters are implanted in the inferior vena cava and in the abdominal aorta of male Sprague-Dawley rats. |
| Formulation & Dosage | Dissolved in 20% aqueous solution of 2-hydroxypropyl-β-cyclodextrin; ≤0.1 μmol/kg · min; i.v. administration |
| References | J Pharmacol Exp Ther. 2001 Oct;299(1):323-31; J Endocrinol. 2006 Oct;191(1):189-95. |