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DR ANTHONY MELVIN CRASTO, Born in Mumbai in 1964 and graduated from Mumbai University, Completed his Ph.D from ICT, 1991,Matunga, Mumbai, India, in Organic Chemistry, The thesis topic was Synthesis of Novel Pyrethroid Analogues, Currently he is working with GLENMARK LIFE SCIENCES LTD, Research Centre as Principal Scientist, Process Research (bulk actives) at Mahape, Navi Mumbai, India. Total Industry exp 30 plus yrs, Prior to joining Glenmark, he has worked with major multinationals like Hoechst Marion Roussel, now Sanofi, Searle India Ltd, now RPG lifesciences, etc. He has worked with notable scientists like Dr K Nagarajan, Dr Ralph Stapel, Prof S Seshadri, Dr T.V. Radhakrishnan and Dr B. K. Kulkarni, etc, He did custom synthesis for major multinationals in his career like BASF, Novartis, Sanofi, etc., He has worked in Discovery, Natural products, Bulk drugs, Generics, Intermediates, Fine chemicals, Neutraceuticals, GMP, Scaleups, etc, he is now helping millions, has 9 million plus hits on Google on all Organic chemistry websites. His friends call him Open superstar worlddrugtracker. His New Drug Approvals, Green Chemistry International, All about drugs, Eurekamoments, Organic spectroscopy international, etc in organic chemistry are some most read blogs He has hands on experience in initiation and developing novel routes for drug molecules and implementation them on commercial scale over a 30 PLUS year tenure till date June 2021, Around 35 plus products in his career. He has good knowledge of IPM, GMP, Regulatory aspects, he has several International patents published worldwide . He has good proficiency in Technology transfer, Spectroscopy, Stereochemistry, Synthesis, Polymorphism etc., He suffered a paralytic stroke/ Acute Transverse mylitis in Dec 2007 and is 90 %Paralysed, He is bound to a wheelchair, this seems to have injected feul in him to help chemists all around the world, he is more active than before and is pushing boundaries, He has 9 million plus hits on Google, 2.5 lakh plus connections on all networking sites, 90 Lakh plus views on dozen plus blogs, 233 countries, 7 continents, He makes himself available to all, contact him on +91 9323115463, email, Twitter, @amcrasto , He lives and will die for his family, 90% paralysis cannot kill his soul., Notably he has 33 lakh plus views on New Drug Approvals Blog in 233 countries...... , He appreciates the help he gets from one and all, Friends, Family, Glenmark, Readers, Wellwishers, Doctors, Drug authorities, His Contacts, Physiotherapist, etc

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Drug from Mediterranean weed kills tumor cells in mice – Thapsia garganica

Just a three-day course  reduced the size of human prostate tumors grown in mice by an average of 50 percent within 30 days

‘Molecular grenade’ now in clinical trials for advanced cancer

12 JUL 2012

Scientists at the Johns Hopkins Kimmel Cancer Center, working with Danish researchers, have developed a novel anticancer drug designed to travel — undetected by normal cells — through the bloodstream until activated by specific cancer proteins. The drug, made from a weedlike plant, has been shown to destroy cancers and their direct blood supplies, acting like a “molecular grenade,” and sparing healthy blood vessels and tissues.

In laboratory studies, researchers said they found that a three-day course of the drug, called G202, reduced the size of human prostate tumors grown in mice by an average of 50 percent within 30 days. In a direct comparison, G202 outperformed the chemotherapy drug docetaxel, reducing seven of nine human prostate…

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FDA approves new drug Cerdelga (eliglustat) to treat a form of Gaucher disease

August 19, 2014


The U.S. Food and Drug Administration today approved Cerdelga (eliglustat) for the long-term treatment of adult patients with the Type 1 form of Gaucher disease, a rare genetic disorder.
Gaucher disease occurs in people who do not produce enough of an enzyme called glucocerebrosidase. The enzyme deficiency causes fatty materials to collect in the spleen, liver and bone marrow. The major signs of Gaucher disease include liver and spleen enlargement, low red blood cell counts (anemia), low blood platelet counts and bone problems.
Cerdelga is a hard gelatin capsule containing eliglustat that is taken orally. In patients with Gaucher disease Type 1, the drug slows down the production of the fatty materials by inhibiting the metabolic process that forms them. Type 1 Gaucher disease is estimated to affect about 6,000 people in the United States.
“Today’s approval offers another important treatment option for patients with Type 1 Gaucher disease,” said Amy G. Egan, M.D., M.P.H., deputy director of the Office of Drug Evaluation III in FDA’s Center for Drug Evaluation and Research. “In addition, Cerdelga received orphan drug designation from the FDA, reflecting the agency’s focus and commitment to the development of treatments for rare diseases.”
The safety and effectiveness of Cerdelga were evaluated in two clinical trials with 199 participants with Type 1 Gaucher disease.
In one randomized, double-blind, placebo-controlled, multicenter clinical trial the safety and effectiveness of Cerdelga were evaluated in 40 participants with Type 1 Gaucher’s disease who had not previously received enzyme replacement therapy. Subjects received the drug at a starting dose of 42 mg two times a day, with most receiving a dose of 84 mg two times a day after four weeks. Study participants continued the drug for nine months.
Compared to placebo, treatment with Cerdelga resulted in a greater reduction in spleen volume from baseline to the end of the study (by the 39th week), the trial’s primary endpoint. Cerdelga also resulted in greater improvement in liver volume, blood platelet count, and red blood cell (hemoglobin) level, compared to placebo.
The other trial sought to determine the safety and effectiveness of Cerdelga compared to enzyme replacement therapy in 159 participants with Type 1 Gaucher disease previously treated and stabilized on enzyme replacement therapy. Subjects in the trial received either the enzyme replacement therapy drug imiglucerase or Cerdelga. The trial demonstrated that treatment with Cerdelga resulted in similar stabilization of hemoglobin level, platelet count and spleen and liver volume as imiglucerase.
The most commonly observed side effects in the Cerdelga clinical trials were fatigue, headache, nausea, diarrhea, back pain, pain in extremities, and upper abdominal pain.
Cerdelga is manufactured by Cambridge, Massachusetts-based Genzyme.


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Wednesday, 20 August 2014 Glenmark enters Oncology with the Discovery and the Initiation of IND enabling Studies of an innovative bispecific Antibody

August 20, 2014: Glenmark Pharmaceuticals S.A. (GPSA), a wholly owned subsidiary of Glenmark Pharmaceuticals Limited India (GPL), announces the discovery and initiation of IND enabling studies of a novel clinical development candidate, GBR 1302, a HER2xCD3 bispecific antibody. GBR 1302 was discovered and developed by the Glenmark Biologics Research Centre located in La Chaux-de-Fonds, Switzerland. GBR 1302 is based on Glenmark’s innovative BEAT antibody technology platform which facilitates the efficient development and manufacture of antibodies with dual specificities, so-called bispecific antibodies. GBR 1302 is the first clinical development candidate based on the BEAT technology. Glenmark expects to obtain approval for the initiation of clinical studies during this financial year.


·GBR 1302 is the first bispecific antibody based on Glenmark’s proprietary BEAT platform

  • GBR 1302 is Glenmark’s first clinical candidate targeting oncology indications

    Glenmark Pharmaceuticals announced the discovery and initiation of IND enabling studies of a novel clinical development candidate, GBR 1302, a HER2xCD3 bispecific antibody. GBR 1302 was discovered and developed by the Glenmark Biologics Research Centre located in La Chaux-de-Fonds, Switzerland. GBR 1302 is based on Glenmark’s innovative BEAT antibody technology platform which facilitates the efficiend development and manufacture of antibodies with dual specificities, so-called bispecific antibodies. GBR 1302 is the first clinical development candidate based on the BEAT technology.Glenmark expect to obtain approval for the initiation of clinical studies during this financial year.

    read at

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Antimicrobial resistance


Antimicrobials are medicines that kill or inactivate microbes, small disease-causing organisms. They include antibiotics, which are used against bacteria. After being exposed to an antimicrobial repeatedly, microbes can undergo changes that stop them being killed or inactivated by the treatments. This is known as antimicrobial resistance.

The European Medicines Agency is concerned about the development of antimicrobial resistance, particularly resistance to antibiotics. A well-known example of a bacterium that is resistant to a number of antibiotics is meticillin-resistant Staphylococcus aureus(MRSA), which has caused infections that are difficult to treat across the European Union (EU).


This problem is being made worse by the fact that few new antimicrobials have been authorised over the past few years. This may lead to infections becoming more difficult to treat in the future.

Antimicrobial resistance is a growing problem in humans and in animals. Resistance can also spread from animals to humans through the food chain or direct contact.

The role of the Agency

The Agency works in collaboration with its EU and international partners in a number of initiatives aiming to limit the development of resistance. It is also monitoring and evaluating the risks to human and animal health.

A major such initiative is the Transatlantic Task Force on Antimicrobial ResistanceExternal link icon(TATFAR), which was established following the EU-United States summit in November 2009. The Task Force aims to increase levels of communication, coordination and co-operation between the EU and the United States on human and veterinary antimicrobials.


Human health

In human medicine, the availability of medicines to treat infections with resistant organisms has become a major problem in recent years.

In September 2009, the Agency published a joint report together with the European Centre for Disease Prevention and ControlExternal link icon (ECDC) and the international network ReAct – Action on Antibiotic ResistanceExternal link icon. This report highlights the gap between infections due to resistant bacteria and the development of new antibiotics.

The report states that at least 25,000 patients in the EU die each year from infections due to bacteria that are resistant to many medicines, and that infections due to these bacteria in the EU result in extra healthcare costs and productivity losses of at least €1.5 billion each year. Although it identified 15 antibiotics under development, most of these were early in development and were targeted against bacteria for which treatment options were already available.


Authorisation of new antibiotics

The Agency plays a key role in the authorisation of new antibiotics, because medicines with a significant therapeutic innovation or that are in the interest of public or animal health are authorised centrally in the EU, on the recommendation of the Agency.

In January 2012, the Agency updated its guidance to companies developing antibiotics, covering how they should carry out studies to test these medicines’ benefits and risks:

This is accompanied by an addendum giving information on how to study medicines for specific indications. The final addendum was published in November 2013 following a public consultation:


Animal health

The Agency is focused on promoting the prudent use of antimicrobials in animals, to limit the development of resistance. This goal is addressed in this document:

In line with this strategy, the Agency published a revised version of its guideline onefficacy for public consultation in May 2013. This draft guideline provides detailed recommendations for the design and conduct of pre-clinical and clinical studies to support clinical efficacy for antimicrobial veterinary products:

Since early 2010, the Agency has been leading a project collecting information on the sale of veterinary antimicrobials across the EU:

The CVMP has also published a large number of documents on microbial resistance in animals and its risks for humans.

Reports published by the Agency together with other European bodies, including ECDC, EFSA and the European Commission’s Scientific Committee on Emerging and Newly Identified Health RisksExternal link icon (SCENIHR) have emphasised the need for the prudent use of antibiotics in animals and the role of basic hygiene, and called for strengthened surveillance of resistance, the development of new antimicrobials and new strategies to combat the spread of resistance:

In 2013 and 2014, the Agency carried out a large body of work to provide advice to the European Commission on the use of antibiotics in animals and the impact on public health and animal health.

Turkish man pleads guilty to importing illegal cancer drugs



August 15, 2014


Sabahaddin Akman, owner of the Istanbul, Turkey, firm Ozay Pharmaceuticals, has pleaded guilty to charges of smuggling misbranded and adulterated cancer treatment drugs into the United States.

Akman pleaded guilty in the U.S. District Court for the Eastern District of Missouri, in St. Louis, Missouri, where he initially shipped his illegal drugs. The drugs did not meet the FDA’s standards and had not been approved for distribution in the United States.

The FDA’s Office of Criminal Investigations coordinated a complex, multi-layered international investigation that led to Akman’s arrest in Puerto Rico in January 2014. The investigation identified Akman and his company as a source of Altuzan, the Turkish version of the cancer treatment drug Avastin.

“These criminals exploited our most vulnerable patients when they arranged for their illicit drugs to be brought into the United States and used to treat cancer patients. We will continue to…

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Road map to 2015, The European Medicines Agency’s contribution to science, medicines and health


One of the European Medicines Agency’s long-term strategic goals is to foster researchand the uptake of innovative methods in the development of medicines.

READ………….Road map to 2015

The European Medicines Agency’s
contribution to science, medicines and health……………..

This helps the Agency to meet its objective of making safe and effective medicines available to patients in a timely manner, following evaluation using state-of-the-art methods.

The Agency also supports the development of new therapies and technologies by working with interested parties in the European Union (EU).

Activities at the Agency

In 2004, the Agency set up the European Medicines Agency/Committee for Medicinal Products for Human Use (CHMP) Think-Tank Group on Innovative Drug Development.

This group included Agency staff and members of the CHMP and its working parties. Its work focused on identifying scientific bottlenecks and emerging science in the development of medicines, both in industry research and development…

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Lupin launches insulin glargine in India

lupin ltd biosimilarnews Lupin launches insulin glargine in India

Lupin launches insulin glargine in India:

Indian pharma company, Lupin Limited announced a strategic distribution agreement with LG Life Sciences of South Korea to launch Insulin Glargine, a novel insulin analogue under the brand name Basugine™.

According to the agreement, Lupin would be responsible for marketing and sales of Basugine™ in India.


Celltrion files Remsima in the United States

Celltrion files Remsima in the United States:

Celltrion announced that the company, on August 8, 2014, completed the filing procedure to obtain US FDA approval for its infliximab biosimilar. This marks the first 351(k) biosimilar mAb application to be filed in the U.S.A. and the second application for a biosimilar to be filed through the US BPCIA.



Chemical structure for zopolrestat


CAS : 110703-94-1
110765-49-6 (Na salt)
3,4-Dihydro-4-oxo-3-[[5-(trifluoromethyl)-2-benzothiazolyl]methyl]-1-phthalazineacetic acid
2- [4-Oxo-3- [5- (trifluoromethyl) benzothiazol-2-ylmethyl] -3,4-dihydrophthalazin-1-yl] acetic acid
2-[4-oxo-3-[5-(trifluoromethyl)benzothiazol-2-ylmethyl]-3,4-dihydrophthalazin-1-yl]acetic acid
Manufacturers’ Codes: CP-73850
MF: C19H12F3N3O3S
MW: 419.38
C 54.41%, H 2.88%, F 13.59%, N 10.02%, O 11.45%, S 7.65%
 Crystals, mp 197-198°. pKa (dioxane/water): 5.46 (1:1); 6.38 (2:1). Log P (n-octanol/water): 3.43.
 mp 197-198°
pKa: pKa (dioxane/water): 5.46 (1:1); 6.38 (2:1)
Log P: Log P (n-octanol/water): 3.43
Therap-Cat: Treatment of diabetic complications.
Keywords: Aldose Reductase Inhibitor.
2-(8-oxo-7-((5-trifluromethyl)-1H-benzo[d]imidazol-2-yl)methyl)7,8-dihydropyrazin[2,3-d]pyridazin-5-yl)acetic acid and [4-oxo-(5-trifluoromethyl-benzothaiazol-2-ylmethyl)-3,4-dihydro-phthalazin-1-yl]-acetic acid (also known as zopolrestat), pharmaceutical compositions thereof and methods of treating diabetic complications in mammals comprising administering to mammals these salt and compositions. 2-(8-oxo-7-((5-trifluromethyl)-1H-benzo[d]imidazol-2-yl)methyl)8-dihydropyrazin[2,3-d]pyridazin-5-yl) acetic acid (formula II), is disclosed in WO 2012/009553 A1. Zopolrestat (formula III) is disclosed in U.S. Pat. No. 4,939,140.
Each of the patents, applications, and other references referred to herein are incorporated by reference. The diabetic complications include neuropathy, nephropathy, retinopathy, cataracts and cardiovascular complications, including myocardial infarction and cardiomyopathy. This invention is also directed to combinations of these salts and antihypertensive agents. These combinations are also useful in treating diabetic complications in mammals.
2-(8-oxo-7-((5-trifluoromethyl)-1H-benzo[d]imidazol-2-yl)methyl)8-dihydropyrazin[2,3-d]pyridazin-5-yl)acetic acid is prepared as disclosed in WO 2012/009553 A1, which is incorporated herein by reference. Zopolrestat is prepared as disclosed in U.S. Pat. No. 4,939,140.
Zopolrestat can be obtained by several different ways: 1) The reaction of 2- (4-oxo-3,4-dihydrophthalazin-1-yl) acetic acid ethyl ester (I) with 2-chloroacetonitrile by means of potassium tert-butoxide in DMF gives 2- [3- (cyanomethyl) -4-oxo-3,4-dihydrophthalazin-1-yl] acetic acid ethyl ester (II), which is cyclized with 2-amino-4- (trifluoromethyl) thiophenol (III) in refluxing ethanol yielding zopolrestat ethyl ester (IV). Finally, this compound is hydrolyzed with KOH in methanol / water / THF. 2) Compound (IV) can also be obtained by cyclization of (II) with 4-chloro-3-nitrobenzotrifluoride . (V) in hot DMF saturated with H2S 3) Compound (II) can also be obtained as follows: The reaction of phthalazine (I) with aqueous formaldehyde gives 2- [3- (hydroxymethyl) -4-oxo-3,4 -dihydrophthalazin-1-yl] acetic acid ethyl ester (VI), which is treated with PBr3 in ethyl ether yielding the bromomethyl derivative (VII). Finally, this compound is treated with potassium cyanide and KI in acetone / water.

  • [0051]
    In accordance with Example 6, the following compounds are prepared:

    Figure imgb0011
    Figure imgb0012
    Figure imgb0013
EXAMPLE 18 Sodium 3-(5-trifluoromethylbenzothiazol-2-ylmethyl)-4-oxo-3H-phthalazin-1-ylacetateSodium methoxide (54 mg) was added to 3-(5-trifluoromethylbenzothiazol-2-ylmethyl)-4-oxo-phthalazin-1-ylacetic acid (0.4 g) in methanol 10 ml) at room temperature. After the addition was complete, a clear solution was obtained which was stirred for 15 minutes at room temperature. The excess methanol was evaporated. The residue was triturated with ether (20 ml) and filtered to obtain the product (0.43 g; m.p. 300° C.).EXAMPLE 19 3-(5-Trifluoromethylbenzothiazol-2-ylmethyl)-4-oxo-3H-phthalazin-1-ylacetate, dicyclohexylamine saltTo a mixture of 3-(5-trifluromethylbenzothiazol-2ylmethyl)-4-oxo-phthalazin-1-ylacetic acid (0.42 g) in methanol (10 ml) was added dicyclohexylamine (0.2 g) in methanol (5 ml). The resulting clear solution was stirred at room temperature for 15 minutes and then evaporated to dryness. Trituration of the residue with ether (30 ml) gave a white solid (0.38 g; m.p. 207° C.).EXAMPLE 20 3-(5-Trifluoromethylbenzothiazol-2ylmethyl)-4-oxo-3H-phthalazin-1-ylacetic acid, meglumine saltA solution of 3-(5-trifluoromethylbenzothiazol-2-ylmethyl)-4-oxo-phthalazin-1-ylacetic acid (419 mg) and meglumine (196 mg) in methanol (50 ml) was stirred at room temperature for an hour and then evaporated to dryness. The residue was triturated with ether (25 ml), filtered and the collected solid was air dried (610 mg; m.p. 157° C.)……………………………

J. Med. Chem., 1991, 34 (1), pp 108–122
DOI: 10.1021/jm00105a018


Mylari, Banavara L.; Zembrowski, William J.; Beyer, Thomas A.; Aldinger, Charles E.; Siegel, Todd W.
Journal of Medicinal Chemistry, 1992 ,  vol. 35,   12  p. 2155 – 2162


Mylari; Beyer; Scott; Aldinger; Dee; Siegel; Zembrowski
Journal of Medicinal Chemistry, 1992 ,  vol. 35,   3  p. 457 – 465


Literature References:
Aldose reductase inhibitor. Prepn: B. L. Mylari et al., EP 222576; E. R. Larson, B. L. Mylari, US 4939140(1987, 1990 both to Pfizer);
B. L. Mylari et al. J. Med. Chem. 34, 108 (1991).
Pharmacology: B. Tesfamariam et al., J. Cardiovasc.Pharmacol. 21, 205 (1993); B. Tesfamariam et al., Am. J. Physiol. 265, H1189 (1993).
Clinical pharmacokinetics: P. B. Inskeep et al., J. Clin. Pharmacol. 34, 760 (1994).
Zopolrestat < Rec INN; BAN; USAN >
Drugs Fut 1995, 20(1): 33
Synthesis of aldose reductase inhibitor, 3, 4-dihydro-4-oxo-3-[[5-(trifluoromethyl)-2 14C benzothiazolyl]methyl]-1-phthalazineacetic acid
J Label Compd Radiopharm 1991, 29(2): 143
Heterocyclic oxophthalazinyl acetic acids
Medical devices to treat or inhibit restenosis
Aldose reductase inhibition in preventing or reversing diabetic cardiomyopathy
Compounds for treating and preventing diabetic complications
Pharmaceutical composition for use in treatment of diabetes
Salts of zopolrestat
Use of an aldose reductase inhibitor for reducing non-cardiac tissue damage

Кальцитонин, Calcitonin


Molecular formula of calcitonin is C145H241N43O49S2
• Molecular weight is 3434.8 g/mol

Calcitonin-related polypeptide alpha
NMR solution structure of salmon calcitonin in SDS micelles.[1]
CAS Registry Number: 9007-12-9
Additional Names: Thyrocalcitonin; TCA; TCT
Therap-Cat: Calcium regulator.


The structural formula


Calcitonin (also known as thyrocalcitonin) is a 32-amino acid linear polypeptide hormone that is produced in humansprimarily by the parafollicular cells (also known as C-cells) of the thyroid, and in many other animals in the ultimobranchial body.[2] It acts to reduce blood calcium (Ca2+), opposing the effects of parathyroid hormone (PTH).[3]

Calcitonin has been found in fishreptilesbirds, and mammals. Its importance in humans has not been as well established as its importance in other animals, as its function is usually not significant in the regulation of normal calcium homeostasis.[4] It belongs to the calcitonin-like protein family.

UV – range

Conditions : Concentration – 53 mg / 100 ml
Solvent designation schedule Methanol
0.1М HCl
0.1M NaOH
The absorption maximum 278 nm 275 nm
4.9 4.4
with 1670 1500




IR – spectrum

Wavelength (μm)
Wavenumber (cm -1 )



  • UV and IR Spectra. H.-W. Dibbern, R.M. Muller, E. Wirbitzki, 2002 ECV
  • NIST/EPA/NIH Mass Spectral Library 2008
  • Handbook of Organic Compounds. NIR, IR, Raman, and UV-Vis Spectra Featuring Polymers and Surfactants, Jr., Jerry Workman. Academic Press, 2000.
  • Handbook of ultraviolet and visible absorption spectra of organic compounds, K. Hirayama. Plenum Press Data Division, 1967.
Calcitonin-related polypeptide alpha
NMR solution structure of salmon calcitonin in SDS micelles.[1]
Available structures
PDB Ortholog search: PDBeRCSB
[show]List of PDB id codes
External IDs OMIM114130 MGI2151253HomoloGene88401 ChEMBL5293GeneCardsCALCA Gene
[show]Gene ontology
RNA expression pattern
PBB GE CALCA 210728 s at tn.png
PBB GE CALCA 210727 at tn.png
PBB GE CALCA 217495 x at tn.png
More reference expression data
Species Human Mouse  
Entrez 796 12310  
Ensembl ENSG00000110680 ENSMUSG00000030669  
UniProt P01258 P70160  
RefSeq (mRNA) NM_001033952 NM_001033954  
RefSeq (protein) NP_001029124 NP_001029126  
Location (UCSC) Chr 11:
14.99 – 14.99 Mb
Chr 7:
114.63 – 114.64 Mb
PubMedsearch [1] [2]  

Biosynthesis and regulation

Calcitonin is formed by the proteolytic cleavage of a larger prepropeptide, which is the product of the CALC1 gene (CALCA). The CALC1 gene belongs to a superfamily of related protein hormone precursors including islet amyloid precursor proteincalcitonin gene-related peptide, and the precursor of adrenomedullin.

Secretion of calcitonin is stimulated by:


The hormone participates in calcium (Ca2+) and phosphorus metabolism. In many ways, calcitonin counteracts parathyroid hormone (PTH).

More specifically, calcitonin lowers blood Ca2+ levels in three ways:

However, effects of calcitonin that mirror those of PTH include the following:

  • Inhibits phosphate reabsorption by the kidney tubules[11]

In its skeleton-preserving actions, calcitonin protects against calcium loss from skeleton during periods of calcium mobilization, such as pregnancy and, especially, lactation.

Other effects are in preventing postprandial hypercalcemia resulting from absorption of Ca2+. Also, calcitonin inhibits food intake in rats and monkeys, and may have CNS action involving the regulation of feeding and appetite.


The calcitonin receptor, found on osteoclasts,[12] and in kidney and regions of the brain, is a G protein-coupled receptor, which is coupled by Gs to adenylate cyclase and thereby to the generation of cAMP in target cells. It may also affect the ovaries in women and the testes in men.


Calcitonin was purified in 1962 by Copp and Cheney.[13] While it was initially considered a secretion of the parathyroid glands, it was later identified as the secretion of the C-cellsof the thyroid gland.[14]


Salmon calcitonin is used for the treatment of:

It has been investigated as a possible non-operative treatment for spinal stenosis.[16]

The following information is from the UK Electronic Medicines Compendium[17]

General characteristics of the active substance

Salmon calcitonin is rapidly absorbed and eliminated. Peak plasma concentrations are attained within the first hour of administration.

Animal studies have shown that calcitonin is primarily metabolised via proteolysis in the kidney following parenteral administration. The metabolites lack the specific biological activity of calcitonin. Bioavailability following subcutaneous and intramuscular injection in humans is high and similar for the two routes of administration (71% and 66%, respectively).

Calcitonin has short absorption and elimination half-lives of 10–15 minutes and 50–80 minutes, respectively. Salmon calcitonin is primarily and almost exclusively degraded in the kidneys, forming pharmacologically inactive fragments of the molecule. Therefore, the metabolic clearance is much lower in patients with end-stage renal failure than in healthy subjects. However, the clinical relevance of this finding is not known. Plasma protein binding is 30% to 40%.

Characteristics in patients

There is a relationship between the subcutaneous dose of calcitonin and peak plasma concentrations. Following parenteral administration of 100 IU calcitonin, peak plasma concentration lies between about 200 and 400 pg/ml. Higher blood levels may be associated with increased incidence of nausea, vomiting, and secretory diarrhea.

Preclinical safety data

Conventional long-term toxicity, reproduction, mutagenicity, and carcinogenicity studies have been performed in laboratory animals. Salmon calcitonin is devoid of embryotoxic, teratogenic, and mutagenic potential.

An increased incidence of pituitary adenomas has been reported in rats given synthetic salmon calcitonin for 1 year. This is considered a species-specific effect and of no clinical relevance. Salmon calcitonin does not cross the placental barrier.

In lactating animals given calcitonin, suppression of milk production has been observed. Calcitonin is secreted into the milk.

Pharmaceutical manufacture

Calcitonin was extracted from the ultimobranchial glands (thyroid-like glands) of fish, particularly salmon. Salmon calcitonin resembles human calcitonin, but is more active. At present, it is produced either by recombinant DNA technology or by chemical peptide synthesis. The pharmacological properties of the synthetic and recombinant peptides have been demonstrated to be qualitatively and quantitatively equivalent.[17]

Uses of calcitonin


Calcitonin can be used therapeutically for the treatment of hypercalcemia or osteoporosis.

Oral calcitonin may have a chondroprotective role in osteoarthritis (OA), according to data in rats presented in December, 2005, at the 10th World Congress of the Osteoarthritis Research Society International (OARSI) in Boston, Massachusetts. Although calcitonin is a known antiresorptive agent, its disease-modifying effects on chondrocytes and cartilage metabolisms have not been well established until now.

This new study, however, may help to explain how calcitonin affects osteoarthritis. “Calcitonin acts both directly on osteoclasts, resulting in inhibition of bone resorption and following attenuation of subchondral bone turnover, and directly on chondrocytes, attenuating cartilage degradation and stimulating cartilage formation,” says researcher Morten Karsdal, MSC, PhD, of the department of pharmacology at Nordic Bioscience in Herlev, Denmark. “Therefore, calcitonin may be a future efficacious drug for OA.”[18]

Subcutaneous injections of calcitonin in patients suffering from mania resulted in significant decreases in irritability, euphoria and hyperactivity and hence calcitonin holds promise for treating bipolar disorder.[19] However no further work on this potential application of calcitonin has been reported.


It may be used diagnostically as a tumor marker for medullary thyroid cancer, in which high calcitonin levels may be present and elevated levels after surgery may indicate recurrence. It may even be used on biopsy samples from suspicious lesions (e.g., lymph nodes that are swollen) to establish whether they are metastasis of the original cancer.

Cutoffs for calcitonin to distinguish cases with medullary thyroid cancer have been suggested to be as follows, with a higher value increasing the suspicion of medullary thyroid cancer:[20]

  • females: 5 ng/L or pg/mL
  • males: 12 ng/L or pg/mL
  • children under 6 months of age: 40 ng/L or pg/mL
  • children between 6 months and 3 years of age: 15 ng/L or pg/mL

When over 3 years of age, adult cutoffs may be used

Increased levels of calcitonin have also been reported for various other conditions. They include: C-cell hyperplasia, Nonthyroidal oat cell carcinoma, Nonthyroidal small cell carcinoma and other nonthyroidal malignancies, acute and chronic renal failure, hypercalcemia, hypergastrinemia and other gastrointestinal disorders, and pulmonary disease.[21]


Calcitonin is a polypeptide hormone of 32 amino acids, with a molecular weight of 3454.93 daltons. Its structure comprises a single alpha helix.[1] Alternative splicing of the gene coding for calcitonin produces a distantly related peptide of 37 amino acids, called calcitonin gene-related peptide (CGRP), beta type.[22]

The following are the amino acid sequences of salmon and human calcitonin:[23]

  • salmon:
  • human:

Compared to salmon calcitonin, human calcitonin differs at 16 residues.

Description: Cellular and molecular coordination of tissues which secrete chemical compounds to regulate growth, reproduction, metabolism, and ion homeostasis.






  1. Jump up to:a b PDB 2glhAndreotti G, Méndez BL, Amodeo P, Morelli MA, Nakamuta H, Motta A (August 2006). “Structural determinants of salmon calcitonin bioactivity: the role of the Leu-based amphipathic alpha-helix”. J. Biol. Chem. 281 (34): 24193–203.doi:10.1074/jbc.M603528200PMID 16766525.
  2. Jump up^ Costoff A. “Sect. 5, Ch. 6: Anatomy, Structure, and Synthesis of Calcitonin (CT)”.Endocrinology: hormonal control of calcium and phosphate. Medical College of Georgia. Retrieved 2008-08-07.
  3.  Boron WF, Boulpaep EL (2004). “Endocrine system chapter”. Medical Physiology: A Cellular And Molecular Approach. Elsevier/Saunders. ISBN 1-4160-2328-3.
  4. Jump up^ Costoff A. “Sect. 5, Ch. 6: Biological Actions of CT”. Medical College of Georgia. Retrieved 2008-08-07.
  5. Costanzo, Linda S. (2007). BRS Physiology. Lippincott, Williams, & Wilkins. p. 263.ISBN 978-0-7817-7311-9.
  6. Jump up^ Erdogan MF, Gursoy A, Kulaksizoglu M (October 2006). “Long-term effects of elevated gastrin levels on calcitonin secretion”J Endocrinol Invest. 29 (9): 771–775.PMID 17114906.
  7.  Costoff A. “Sect. 5, Ch. 6: Effects of CT on the Small Intestine”. Medical College of Georgia. Retrieved 2008-08-07.
  8.  Costoff A. “Sect. 5, Ch. 6: Effects of CT on Bone”. Medical College of Georgia. Retrieved 2008-08-07.
  9. Jump up^ Potts, John; Jüppner, Harald (2008). “Chapter 353. Disorders of the Parathyroid Gland and Calcium Homeostasis”. In Dan L. Longo, Dennis L. Kasper, J. Larry Jameson, Anthony S. Fauci, Stephen L. Hauser, and Joseph Loscalzo. Harrison’s Principles of Internal Medicine (18 ed.). McGraw-Hill.
  10.  Rhoades, Rodney (2009). Medical Physiology: Principles for Clinical Medicine. Philadelphia: Lippincott Williams & Wilkins. ISBN 978-0-7817-6852-8.
  11. Jump up^ Carney SL (1997). “Calcitonin and human renal calcium and electrolyte transport”.Miner Electrolyte Metab 23 (1): 43–7. PMID 9058369.
  12. Jump up^ Nicholson GC, Moseley JM, Sexton PM, et al (1986). “Abundant calcitonin receptors in isolated rat osteoclasts. Biochemical and autoradiographic characterization”J Clin Invest 78 (2): 355–60. doi:10.1172/JCI112584PMC 423551PMID 3016026.
  13. Jump up^ Copp DH, Cheney B (January 1962). “Calcitonin-a hormone from the parathyroid which lowers the calcium-level of the blood”. Nature 193 (4813): 381–2.doi:10.1038/193381a0PMID 13881213.
  14. Jump up^ Hirsch PF, Gauthier GF, Munson PL (August 1963). “Thyroid hypocalcemic principle and recurrent laryngeal nerve injury as factors affecting the response to parathyroidectomy in rats”. Endocrinology 73 (2): 244–252. doi:10.1210/endo-73-2-244.PMID 14076205.
  15. Jump up^ Wall GC, Heyneman CA (April 1999). “Calcitonin in phantom limb pain”. Ann Pharmacother 33 (4): 499–501. doi:10.1345/aph.18204PMID 10332543.
  16. Jump up^ Tran de QH, Duong S, Finlayson RJ (July 2010). “Lumbar spinal stenosis: a brief review of the nonsurgical management”. Can J Anaesth 57 (7): 694–703. doi:10.1007/s12630-010-9315-3PMID 20428988.
  17. Jump up to:a b “Electronic Medicines Compendium”. Retrieved 2008-08-07.
  18. Jump up^ Kleinman DM (2006-01-04). “Oral Calcitonin May Delay Onset of Joint Disease and Relieve Pain of OA”Musculoskeletal Report. Musculoskeletal Report, LLC. Retrieved 2008-08-07.
  19. Jump up^ Vik A, Yatham LN (March 1998). “Calcitonin and bipolar disorder: a hypothesis revisited”J Psychiatry Neurosci 23 (2): 109–17. PMC 1188909PMID 9549251.
  20. Jump up^ Basuyau, J. -P.; Mallet, E.; Leroy, M.; Brunelle, P. (2004). “Reference Intervals for Serum Calcitonin in Men, Women, and Children”. Clinical Chemistry 50 (10): 1828–1830.doi:10.1373/clinchem.2003.026963PMID 15388660edit
  21. Jump up^ Burtis CA, Ashwood ER, Bruns DE. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics, 5th edition. Elsevier Saunders. p. 1774. ISBN 978-1-4160-6164-9.
  22. Jump up^ “calcitonin domain annotation”SMART (a Simple Modular Architecture Research Tool). Retrieved 2009-02-22.
  23. Jump up^

Further reading

External links

Literature References: 
Calcium regulating hormone secreted from the mammalian thyroid gland and in non-mammalian species from the ultimobranchial gland. Postulation of a plasma-calcium lowering substance: Copp et al., Endocrinology 70, 638 (1962).
Recognition as a hormone: Hirsch et al., ibid. 73, 244 (1963); of thyroid origin: Foster et al., Nature 202, 1303 (1964).
Over-all action is to oppose the bone and renal effects of parathyroid hormone, q.v.; inhibits bone resorption of Ca2+, with accompanying hypocalcemia and hypophosphatemia and decreased urinary Ca2+ concentrations. Also abolishes the osteolytic effect of toxic doses of vitamins A and D. Calcitonin is highly active biologically, e.g. 50 mg/min infused into a 100 g rat leads to a significant (1 mg/100 ml) decrease in the concn of the plasma calcium within 60 min (together with a corresponding fall in plasma phosphate). Activity is destroyed by trypsin, chymotrypsin, pepsin, polyphenol oxidase; also by hydrogen peroxide oxidation, photooxidation, and treatment with N-bromosuccinimide. Calcitonin structures are single polypeptide chains containing 32 amino acid residues. Structure of porcine: Neher et al., Helv. Chim. Acta 51, 917 (1968); Potts et al., Proc. Natl. Acad. Sci. USA 59, 1321 (1968); Bellet al., J. Am. Chem. Soc. 90, 2704 (1968); eidem, Biochemistry 9, 1665 (1970).
Synthesis of porcine: Rittel et al., Helv. Chim. Acta 51, 924 (1968); Guttmann et al., ibid. 1155.
Isoln of human calcitonin from non-pathological thyroid glands: Haymovits, Rosen, Endocrinology 81, 993 (1967); from medullary carcinoma of the thyroid: Neher et al., Nature 220, 984 (1968); Helv. Chim. Acta 51, 1738 (1968); Neher, Riniker, DE 1929957 (1970 to Ciba), C.A. 73, 28902b (1970).
Structure of human: Neher et al., Helv. Chim. Acta 51, 1900 (1968). Synthesis of human: Sieber et al., ibid. 2057; J. Hirt et al., Rec. Trav. Chim. 98, 143 (1979).
Biosynthetic studies: J. W. Jacobs et al., J. Biol. Chem. 254, 10600 (1979); S. G. Amara et al., ibid. 255, 2645 (1980).
Amino acid sequence differs among mammalian species, salmon calcitonin showing a marked difference from that of the higher vertebrae as well as a more potent biological activity. Mechanism of action: E. M. Brown, G. D. Aurbach, Vitam. Horm. 38, 236 (1980). Anorectic activity in rats: W. J. Freed et al., Science 206, 850 (1979).
Growth inhibition of human breast cancer cells in vitro: Y. Iwasaki et al., Biochem. Biophys. Res. Commun. 110, 235 (1983).
Review of early literature: Munson, Hirsch, Clin. Orthop. 49, 209 (1966).
Review of isoln, structure, synthesis: Behrens, Grinnan, Annu. Rev. Biochem. 38, 83 (1969); Potts et al., Vitam. Horm. 29,41 (1971).
Comprehensive review: Calcitonin, Proc. Symp. on Thyrocalcitonin and the C Cells, S. Taylor, Ed. (Springer-Verlag, New York, 1968); Foster et al., ”Calcitonin” in Clinics in Endocrinology and Metabolism, I. MacIntyre, Ed. (W. B. Saunders, Philadelphia, 1972) pp 93-124.
Review of pharmacology and therapeutic use: J. C. Stevenson, I. M. A. Evans, Drugs 21, 257-272 (1981).
Derivative Type: Calcitonin, porcine
CAS Registry Number: 12321-44-7
Trademarks: Calcitar(e) (RPR); Staporos (Cassenne)
Derivative Type: Calcitonin, human synthetic
CAS Registry Number: 21215-62-3
Trademarks: Cibacalcin (Novartis)
Derivative Type: Calcitonin, salmon synthetic
CAS Registry Number: 47931-85-1
Additional Names: Salcatonin
Trademarks: Calciben (Firma); Calcimar (RPR); Calsyn (RPR); Calsynar (RPR); Catonin (Magis); Karil (Novartis); Miacalcic (Novartis); Miacalcin (Novartis); Miadenil (Francia); Osteocalcin (Tosi); Prontocalcin (Domp?; Rulicalcin (HMR); Salmotonin (Yamanouchi); Stalcin (Locatelli); Tonocalcin (Searle)
Literature References: Clinical trial in postmenopausal osteoporosis: C. H. Chesnut et al., Am. J. Med. 109, 267 (2000). LC determn in biological fluids: M. Aguiar et al.J. Chromatogr. B 818, 301 (2005).
Properties: See also Elcatonin.
cas   57014-02-5
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