Cinacalcet

Cinacalcet is a critical calcimimetic pharmaceutical intermediate and API used in the treatment of secondary hyperparathyroidism in patients with chronic kidney disease and parathyroid carcinoma. As an allosteric agonist of the calcium-sensing receptor, Cinacalcet increases the sensitivity of the receptor to extracellular calcium, leading to reduced parathyroid hormone secretion and decreased serum calcium and phosphorus levels. The clinical success of Cinacalcet has established it as a standard-of-care therapy for secondary hyperparathyroidism, marketed under the trade names Sensipar® and Mimpara®. In quality control contexts, Cinacalcet and its related substances—including N-nitroso cinacalcet, dimeric impurities, and various process-related impurities—are critical reference standards for analytical method development, method validation, and quality control applications. As a key calcimimetic therapeutic, Cinacalcet continues to be essential for managing mineral and bone disorders in patients with renal disease.

 

Product Parameters

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Parameter	Specification
Product Name	Cinacalcet
CAS Number	226256-56-0
Molecular Formula	C₂₂H₂₂F₃N
Molecular Weight	357.42 g/mol
Appearance	White to off-white crystalline solid
Boiling Point	440.9 ± 45.0 °C (Predicted)
Density	1.154 ± 0.06 g/cm³ (Predicted)
Storage Condition	Keep in dark place, sealed in dry, 2–8 °C

 

Mechanism Of A ction

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Parathyroid hormone (PTH) is a basic single-chain polypeptide hormone secreted by parathyroid chief cells, composed of 84 amino acids. It plays a crucial role in elevating blood calcium levels, reducing blood phosphorus levels, and regulating the balance of calcium and phosphorus metabolism in vertebrates. Within parathyroid chief cells, the first precursor substance for PTH synthesis is termed proparathyroid hormone (PPH), containing 115 amino acids. This precursor subsequently cleaves intracellularly to form the second precursor, parathyroid hormone (PTH), which consists of 90 amino acids. PTH then further cleaves within the cell to produce the final 84-amino-acid peptide. The normal plasma concentration of PTH in humans is approximately 1 nanogram per milliliter. The primary physiological functions of PTH include promoting bone resorption, mobilizing bone calcium into the bloodstream, increasing blood calcium levels, and enhancing the activity of alkaline phosphatase in bones and blood; inhibiting renal tubular reabsorption of phosphate, thereby increasing urinary phosphorus excretion and lowering blood phosphorus levels; and indirectly stimulating intestinal mucosal absorption of calcium, magnesium, and phosphorus by activating vitamin D3. PTH secretion is primarily regulated by blood calcium concentrations: increased blood Ca²⁺ levels reduce PTH secretion, whereas decreased Ca²⁺ levels stimulate it. Additionally, elevated blood phosphorus levels can induce PTH secretion by lowering blood calcium, as can the substantial release of calcitonin.

The measurement of serum parathyroid hormone (PTH) is not only utilized in the study of parathyroid disorders but also holds significant value in differentiating the etiologies of hypercalcemia and hypocalcemia. Its primary clinical implications include:

1. aiding in the diagnosis of parathyroid diseases; elevated PTH levels are observed in cases of hyperparathyroidism or ectopic PTH secretion, whereas decreased PTH levels are seen in hypoparathyroidism, parathyroid injury due to surgery or radiotherapy, among other conditions.

 

2. Differentiate between hypercalcemia and hypocalcemia. Abnormal blood calcium levels caused by parathyroid dysfunction typically fluctuate in tandem with serum PTH levels, whereas abnormalities due to other etiologies do not alter PTH levels.

 

Bioactivity

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Cinacalcet (AMG 073) is an orally administered calcium receptor (CaR) agonist used in cardiovascular disease research.

 

Product Advantages

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Allosteric Agonist of Calcium-Sensing Receptor

Cinacalcet is a calcimimetic that acts as an allosteric agonist of the calcium-sensing receptor (CaSR). By increasing the sensitivity of CaSR to extracellular calcium, Cinacalcet reduces parathyroid hormone secretion, parathyroid gland weight, and serum calcium levels.

 

 Clinically Validated for Secondary Hyperparathyroidism

Cinacalcet is FDA-approved for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease on dialysis and for the treatment of parathyroid carcinoma. Marketed as Sensipar® and Mimpara®, Cinacalcet has established the calcimimetic class as a standard of care for mineral and bone disorders.

 

 Chiral Amine with High CaSR Affinity

The (R) configuration at the chiral amine center in Cinacalcet is essential for high-affinity binding to the calcium-sensing receptor. The naphthylethylamine and trifluoromethylphenyl pharmacophores work synergistically to achieve potent allosteric modulation.

 

 Dual-Use: API and Impurity Reference Standard

Cinacalcet serves as both the active pharmaceutical ingredient for hyperparathyroidism therapy and a reference standard for analytical method development. Related impurities—including N-nitroso cinacalcet, dimeric impurities, and various process-related impurities—are critical reference standards for spiking studies, method validation, and impurity profiling.

 

 Essential for Renal Disease Management

Cinacalcet is essential for managing secondary hyperparathyroidism in patients with chronic kidney disease, reducing the risk of bone disease, cardiovascular calcification, and other complications of mineral and bone disorders.

 

Contact Us

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Need Cinacalcet for your calcimimetic therapeutic manufacturing, impurity profiling program, or analytical method development? Cosperpharm is your trusted partner. Contact us today to discuss your specifications, request a quote, or schedule a quality audit.