Calcitonin CAS 9007-12-9
Introduction：Basic information about Calcitonin CAS 9007-12-9, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
Calcitonin Basic informationGene structure and mRNA Synthesis and release Receptors Agonists and Antagonists Application in Particular Diseases
| Product Name: | Calcitonin |
| Synonyms: | calcimar(salmon);calcitar;calcitrin;SALMON;CYS-SER-ASN-LEU-SER-THR-CYS-VAL-LEU-GLY-LYS-LEU-SER-GLN-GLU-LEU-HIS-LYS-LEU-GLN-THR-TYR-PRO-ARG-THR-ASN-THR-GLY-SER-GLY-THR-PRO-NH2;CYS-SER-ASN-LEU-SER-THR-CYS-VAL-LEU-GLY-LYS-LEU-SER-GLN-GLU-LEU-HIS-LYS-LEU-GLN-THR-TYR-PRO-ARG-THR-ASN-THR-GLY-SER-GLY-THR-PRO-NH2 SALMON;CSNLSTCVLGKLSQELHKLQTYPRTNTGSGTP-NH2;CSNLSTCVLGKLSQELHKLQTYPRTNTGSGTP-NH2 (DISULFIDE BRIDGE: 1-7) |
| CAS: | 9007-12-9 |
| MF: | C145H240N44O48S2 |
| MW: | 3431.85 |
| EINECS: | 232-693-2 |
| Product Categories: | |
| Mol File: | 9007-12-9.mol |
Calcitonin Chemical Properties
| storage temp. | −20°C |
| solubility | 0.05 M acetic acid: 1 mg/mL, clear, colorless |
| form | powder |
Safety Information
| Safety Statements | 22-24/25 |
| WGK Germany | 3 |
| RTECS | EV8000000 |
| F | 3-10 |
| Hazardous Substances Data | 9007-12-9(Hazardous Substances Data) |
| Gene structure and mRNA | The human CT gene, located on chromosome 11p15.2-p15.1, consists of six exons and five introns. CT mRNA iscoencoded with calcitonin gene-related peptide (CGRP)mRNA in the single gene. In mammals, the synthesisof the mRNAs encoding these two hormones is controlledby tissue-specific alternative splicing. The CT precursormRNA is synthesized in thyroidal C-cells, whereas theCGRP precursor mRNA is synthesized in neural tissues. The pufferfish ct gene consists of four coding exons. The splicing of exons 1, 2, and 3 yields CT,whereas that of exons 1, 2, and 4 yields CGRP. |
| Synthesis and release | CT synthesis in thyroid C-cells and its release are stimulated principally by increased blood calcium levels. Infish as well as mammals, a calcium-sensing receptorhas been cloned. In fasted eels, plasma CT levels werenot detectable by the specific sandwich ELISA technique(detection limit: 30 pg/mL). In eels that were fed a highamount of calcium-consomme solution (Ca2+: 1.25M;1mL/100 g body weight), the plasma CT concentrationincreased rapidly (CT: below detection level at 0 h to1118.2 pg/mL at 3 h) corresponding to increased plasmacalcium levels. In fish as well as mammals, the trigger forCT secretion appears to be primarily a change in bloodcalcium levels. Recently, CT was synthesized in the osteoblasts of goldfish scales. The secretion of CT was promoted by melatonin. This regulation was alsoobserved in the calvariae of rats. |
| Receptors | The calcitonin receptor (CTR) is a member of a subfamily of the seven-transmembrane domain GPCR superfamily that includes several peptide receptors. Porcine CTRcDNA was obtained for the first time in 1991. Subsequentcloning of the gene demonstrated that it is approximately70 kb in length, and contains at least 14 exons, 12 of whichencode procine CTR. Different isoforms of CTR resultingfrom alternative splicing of the gene have been describedin various animal species with differential tissue expression of the transcripts. The human CTR gene has beenmapped to chromosome 7q21.3. CTRs have been identified from various vertebrates. Invertebrate CTR has alsobeen sequenced from the protochordate, Ciona intestinalis.Invertebrate CTs and CTR are described in another section. The value of the dissociation constant (Kd) in ratsand trout CTR was 0.25 to 3.3 nM. |
| Agonists and Antagonists | The relative potency of the agonistic effects are salmon CT=eel CT>human CT<porcine CT. CT family peptide hormones such as CGRP and AMY also have agonist activity. Salmon CT8–32(VLGKLSQELHKLQTYPRTNTGSGTP) and AC512(Lys10-Bolton Hunter, R18N30Y32- salmon CT9–32) haveantagonist activity. |
| Application in Particular Diseases | In Osteoporosis:
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| Description | Calcitonin has been approved for the treatment of postmenopausalosteoporosis, hypercalcemia of malignancy, and Paget's disease of the bone.Several sources are available(e.g., eel, human, salmon, and porcine). The calcitonin isolated from salmon is the preferred source, because ithas greater receptor affinity and a longer half-life than the human hormone. |
| Chemical Properties | Calcitonin is a single-chain polypeptide composed of 32amino acid residues having a molecular weight of approximately3600. A cysteine disulfide bridge at the 1-7position of the amino terminal end of the peptide is essentialfor biological activity; however, the entire aminoacid sequence is required for optimal activity. |
| Originator | Calcitar,Yamanouchi,Japan,1978 |
| Uses | Regulator (calcium). |
| Indications | Calcitonin (Miacalcin, Miacalcin Nasal Spray) is a synthetic32–amino acid polypeptide that is identical tosalmon calcitonin. Salmon calcitonin is more potentthan human calcitonin because of its higher affinity forthe human calcitonin receptor and its slower metabolicclearance. Administration is by subcutaneous or intramuscularinjection or by nasal spray. The absorption ofthe nasal form is slower than that of the parenteralroutes. |
| Indications | Calcitonin release is normally stimulated by risingserum calcium levels and suppressed by hypocalcemia.The major physiological effects of calcitonin are inhibitionof bone resorption and deposition of postabsorptivecalcium into bone following a meal, which preventspostprandial hypercalcemia. |
| Manufacturing Process | The process for the manufacture of human calcitonin in pure form from C-cellrich medulla carcinoma of the thyroid gland or from C-cell metastasis materialis one wherein medullar carcinoma of the thyroid gland or C-cell metastasismaterial, which has been defatted, for example with acetone or ether, andwhich may have been first purified with alcohol or with aqueous trichloroaceticacid, is extracted one or more times with a solvent system containing waterand an alkanol having at most 5 carbon atoms, at a pH of from about 1 to 6,and the extracted product subjected to gel chromatography using aqueousformic acid as eluant. The calcitonin may be separated into its constituents bycountercurrent distribution, for example by Craig distribution using a solventsystem advantageously containing n-butanol and acetic acid. |
| Brand name | Calcimar (Rhone-Poulenc Rorer);. |
| Therapeutic Function | Calcium regulator |
| Biosynthesis | The regulation of calcitonin synthesis and release fromthe parafollicular C cells of the thyroid gland is calciumdependent. Rising serum calcium is the principalstimulus responsible for calcitonin synthesis and release.Other hormones, such as glucagon, gastrin, andserotonin, also stimulate calcitonin release. Calcitoninhas been isolated in tissues other than the parafollicularC cells (parathyroid, pancreas, thymus, adrenal),but it is not known whether this material is biologicallyactive. Secretagogues, such as gastrin and pancreozymin,may contribute significantly to the regulation of endogenouscalcitonin. In fact, it has been postulated thatgastrin-induced calcitonin release following meals mayhelp regulate the postprandial calcium deposition inbone. A calcitonin precursor has been identified within thethyroid parafollicular C cells. It is thought to function ina manner analogous to that of proPTH to facilitate intracellulartransport and secretion of the hormone. Themetabolic degradation of calcitonin appears to occur inboth the liver and kidney. Although blood calcitonin levels are normally low,excessive levels have been found in association withmedullary carcinoma of the thyroid and more rarelycarcinoid tumors of the bronchus and stomach. Serumcalcitonin levels are used to screen and monitor patientswho have or are suspected of having medullary carcinomaof the thyroid. |
| Biological Functions | In addition to its antiresorptive action via suppression of osteoclast activity, calcitonin-salmon exhibits a potentanalgesic effect and has provided considerable relief to those patients suffering from the pain associated withPaget's disease and osteoporosis. This analgesic effect is a result of calcitonin-stimulated endogenous opioidrelease. The potency of this analgesic effect has been demonstrated to be 30- to 50-fold that of morphine inselected patients. Calcitonin is preferred over estrogen and the bisphosphonates when treatment of bothosteoporosis and related bone pain is warranted. |
| Acquired resistance | Resistance to calcitonin-salmon can result from the development of neutralizing antibodies. |
| General Description | Calcitonin (thyrocalcitonin) is a 32-amino-acid polypeptidehormone secreted by parafollicular cells of the thyroidglands in response to hypocalcemia. The entire 32-residuepeptide appears to be required for activity, because smallerfragments are totally inactive. Common structural featuresof calcitonin isolated from different species are a COOHterminalprolinamide, a disulfide bond between residues 1and 7 at the NH2 terminus, and a chain length of 32 residues.Calcitonin inhibits calcium resorption from bone, causinghypocalcemia, with parallel changes in plasma phosphateconcentration. In general, calcitonin negates the osteolyticeffects of parathyroid hormone. The potential therapeutic uses of calcitonin are in thetreatment of hyperparathyroidism, osteoporosis and otherbone disorders, hypercalcemia of malignancy, and idiopathichypercalcemia. |
| Mechanism of action | Calcitonin interacts with specific plasma membrane receptorswithin target organs to initiate biological effects.This interaction has been directly linked to thegeneration of cAMP via adenylyl cyclase activation. |
| Pharmacokinetics | Calcitonin-salmon differs structurally from human calcitonin at 16 of 32amino acids. Thepharmacological activity of these calcitonins is the same, but calcitonin-salmon is approximately 50-fold morepotent on a weight basis than human calcitonin with a longer duration of action. The duration of action forcalcitonin salmon is 8 to 24 hours following intramuscular (IM) or subcutaneous (SC) administration and 0.5 to12.0 hours following IV administration. The parenteral dose required for the treatment of osteoporosis is 100IU/day. Initially only available by IM or SC injection, the peptide hormone calcitonin-salmon is available asa nasal spray (Miacalcin) and as a rectal suppository. A recombinant DNA form of calcitonin salmon wasapproved by the U.S. FDA in 2005 and is available as a nasal spray. The bioavailability of calcitonin-salmonnasal spray shows great variability (range, 0.3–30.6% of an IM dose). It is absorbed rapidly from the nasalmucosa, with peak plasma concentrations appearing 30 to 40 minutes after nasal administration, compared with16 to 25 minutes following parental dosing. Calcitonin-salmon is readily metabolized in the kidney, with anelimination half-life calculated at 43 minutes. As a result, the intranasal dose required is 200 IU/day. Oncethe Miacalcin nasal pump has been activated, the bottle may be kept at room temperature until the medicationis finished (2 weeks) |
| Clinical Use | Calcitonin therapy requires the concomitant oral administration of elemental calcium (500 mg/day). Clinicalstudies have shown that the combination of intranasal calcitonin salmon (200 IU/day), oral calciumsupplementation (>1,000 mg/day of elemental calcium), and vitamin D (400 IU/day) has decreased the rate ofnew fractures by more than 75% and has improved vertebral BMD by as much as 3% annually. Calcitoninprevents the abnormal bone turnover characteristic of Paget's disease of the bone and has antiresorptiveactivity. In the presence of calcitonin, the osteoclast brush borders disappear, and the osteoclasts move awayfrom the bone surface undergoing remodeling. Side effects are significantly more pronounced whencalcitonin-salmon is administered by injection and can include nausea, vomiting, anorexia, and flushing.Because calcitonin-salmon is protein in nature, the possibility of a systemic allergic reaction should beconsidered,and appropriate measures for treatment of hypersensitivity reaction should be readily available. Althoughcalcitonin-salmon does not cross the placenta, it may pass into breast milk. Calcitonin-salmon is a possiblealternative to ERT; however, only limited evidence suggests that it has efficacy in women who already havefractures. |
Calcitonin Preparation Products And Raw materials
| Raw materials | Chloroform-->1-Butanol-->Celite-->3-Methyl-1-butanol-->TRIS BORATE EDTA BUFFER, 10X, DNASE, RNASE AND PROTEASE FREE, PH 8.3, FOR MOLECULAR BIOLOGY-->thyroid powder-->FINITE FILTER |
