Hyperparathyroidism|Inhibitors Agonists Modulators Antagonists|HmoBio.com

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Hyperparathyroidism is a common disorder characterized by excessive secretion of parathyroid hormone (PTH) and resultant hypercalcemia. Primary hyperparathyroidism typically occurs in the setting of hypercellular growth of one or more parathyroid glands, associated with dysregulation of PTH release. Rarely, ectopic secretion of PTH by a nonparathyroid tumor has been described. Primary hyperparathyroidism may occur in the context of the inherited familial syndromes multiple endocrine neoplasia types 1, 2, and 4 (MEN 1, 2, and 4); the hereditary hyperparathyroidism–jaw tumor syndrome (HPT-JT); familial hypocalciuric hypercalcemia (FHH); and neonatal severe hyperparathyroidism (NSHPT), and, when it is the only recurrent clinical manifestation of disease within a family, familial isolated hyperparathyroidism (FIHPT). Most commonly, parathyroid neoplasia is sporadic and caused by a single benign adenoma. Insights into the molecular pathogenesis of both familial and sporadic primary hyperparathyroidism will be covered in this chapter.

Causes

There are 4 tiny parathyroid glands in the neck, near or attached to the back side of the thyroid gland.

The parathyroid glands help control calcium use and removal by the body. They do this by producing parathyroid hormone (PTH). PTH helps control calcium, phosphorus, and vitamin D levels in the blood and bone.

When calcium level is too low, the body responds by making more PTH. This causes the calcium level in the blood to rise.

When one or more of the parathyroid glands grow larger, it leads to too much PTH. Most often, the cause is not known.

~The disease is most common in people over age 60, but it can also occur in younger adults. Hyperparathyroidism in childhood is very unusual.

Women are more likely to be affected than men.

~Radiation to the head and neck increases the risk.

~Some genetic syndromes (multiple endocrine neoplasia I) make it more likely to have hyperparathyroidism.

~In very rare cases, the disease is caused by parathyroid cancer.

Cat. No.	Product Name	CAS No.	Information
H6000	Paricalcitol	131918-61-1	An analog of 1,25-dihydroxyergocalciferol that acts as a selective vitamin D receptor (VDR) activator; significantly decreases parathyroid hormone levels with no changes in calcium and phosphorous, also reduces serum concentrations of IL-6 and TNF-α compared to baseline; orally active.
H5997	Falecalcitriol	83805-11-2	A hexafluorinated analogue of 1,25(OH)2 vitamin D3, has been reported to be several times more potent than the parent compound regarding some vitamin D actions.
H5994	Doxercalciferol	54573-75-0	A synthetic analog of vitamin D with potential antineoplastic activity; has also been shown to inhibit the growth of retinoblastomas, and may exhibit some antiproliferative activity against prostate cancer cells.
H3878	PCO371	1613373-33-3	PCO371 is a potent, selective, orally active, full agonist of the PTH type 1 receptor (PTHR1) with EC50 of 2.4 uM in cell-based assays, does not affect PTHR2; exhibits PTH-like biological activity in osteopenic ovariectomized (OVX) rats and in hypocalcemic thyroparathyroidectomized (TPTX) rats after oral administration; increases bone mineral density (BMD) and bone strength as effectively as PTH by intravenous administration in vivo.
H3057	Velcalcetide	1262780-97-1	Velcalcetide (AMG-416, Velcalcetide, Etelcalcetide, KAI-4169) is a potent, peptide agonist of CaSR, dose-dependenty increases IP1 accumulation with EC50 of 25 uM in cell based assays; reduces parathyroid hormone (PTH) levels and corresponding decreases serum calcium, regardless of the baseline level of PTH in vivo.
H3056	Tecalcet hydrochloride	177172-49-5	Tecalcet (R-568;NPS R-568;KRN-568;NPS-568) is a calcimimetic acting agent and potent, selective positive allosteric modulator (agonist) of CaSR; potentiates the effects of extracellular Ca2+ on [Ca2+]i and PTH secretion without effect in the absence of extracellular Ca2+, does not affect responses elicited by the homologous mGluRs; prevents parathyroid hyperplasia in rats with severe secondary hyperparathyroidism.
H3055	Tecalcet	148717-54-8	Tecalcet (R-568;NPS R-568;KRN-568;NPS-568) is a calcimimetic acting agent and potent, selective positive allosteric modulator (agonist) of CaSR; potentiates the effects of extracellular Ca2+ on [Ca2+]i and PTH secretion (IC50=27 nM in bovine parathyroid cells) without effect in the absence of extracellular Ca2+, does not affect responses elicited by the homologous mGluRs.
H3048	Cinacalcet hydrochloride	364782-34-3	A calcimimetic agent that acts as an allosteric activator of CaSR; increases the concentration of cytoplasmic Ca(2+) in human embryonic kidney 293 cells expressing the human parathyroid CaR with EC50 of 51 nM; decreases PTH secretion from cultured bovine parathyroid cells with IC50 of 28 nM; is used for the treatment of tertiary hyperparathyroidism.
H3047	Cinacalcet	226256-56-0	A calcimimetic agent that acts as an allosteric activator of CaSR; increases the concentration of cytoplasmic Ca(2+) in human embryonic kidney 293 cells expressing the human parathyroid CaR with EC50 of 51 nM; decreases PTH secretion from cultured bovine parathyroid cells with IC50 of 28 nM; is used for the treatment of tertiary hyperparathyroidism.

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