83150-76-9 Usage
Description
Octreotide acetate is a synthetic long-acting cyclic octapeptide that functions as a somatostatin analog, mimicking the pharmacological properties of the natural hormone somatostatin. It is a potent inhibitor of hormone secretion, including growth hormone, glucagon, insulin, gastrin, vasoactive intestinal peptide, secretin, motilin, and pancreatic polypeptide.
Used in Pharmaceutical Industry:
Octreotide acetate is used as a therapeutic agent for symptomatic control in acromegaly and gastroenteropancreatic tumors. It is effective in managing severe diarrhea and flushing associated with malignant carcinoid tumors, acromegaly, and diarrhea associated with VIPoma. Additionally, it was approved in 2010 for the treatment of neuroendocrine tumors.
Octreotide acetate is also being investigated for its potential use in treating diabetes, psoriasis, and Alzheimer's disease, showcasing its versatility in addressing various medical conditions.
Originator
Sandoz (Switzerland)
Indications
Octreotide acetate (Sandostatin) is a synthetic peptide
analogue of the hormone somatostatin. Its actions include
inhibition of the pituitary secretion of growth
hormone and an inhibition of pancreatic islet cell secretion
of insulin and glucagon. Unlike somatostatin, which
has a plasma half-life of a few minutes, octreotide has a
plasma elimination half-life of 1 to 2 hours. Excretion of
the drug is primarily renal.
Therapeutic Function
Antiulcer, Growth hormone inhibitor
Biological Functions
Octreotide acetate, a long-acting octapeptide analogue of somatostatin, has a half-life of
approximately 100 minutes. A comparison of the primary structures of octreotide and
somatostatin suggests little similarity, but from earlier work at the Salk Institute it was known
that not all the residues in somatostatin were necessary to elicit its full biological activity. Other
studies suggested that the essential fragment for its activity was the tetrapeptide Phe7-Trp8-
Lys9-Thr10. These earlier studies helped in the design of the potent drug now known as octreotide acetate. This drug suppresses the secretion of gastroenteropancreatic
peptides, such as gastrin, vasoactive intestinal peptide (VIP), insulin, and glucagon, as well as
pituitary GH. Furthermore, it is more potent than natural somatostatin in inhibiting the release of
glucagon, insulin, and GH.
Biochem/physiol Actions
Octreotide is three times more potent than the native hormone in inhibiting the secretion of growth hormone glucagon and insulin in vivo. Octreotide regulates serum prolactin levels and resolves galactorrhea or (secondary) amenorrhea in acromegaly patients. Hence, this peptide can be considered as a potent therapeutic for acromegaly treatment.
Clinical Use
Octreotide acetate is used by SC injection in the palliative treatment of patients with metastatic
carcinoid tumors, which are tumors of the endocrine system, GI tract, and lung
(gastroenteropancreatic). Carcinoid tumors secrete increasing amounts of vasoactive
substances, including histamine, serotonin, bradykinin, and prostaglandins. Octreotide acetate
inhibits or suppresses the release of these vasoactive substances and, thus, is useful in treating
the severe diarrhea, facial flushing, and wheezing episodes that accompany carcinoid tumors. In
addition, it finds use in the palliative management of VIP-secreting tumors (VIPomas, usually
pancreatic tumors). Patients with VIPomas suffer a profuse, watery diarrhea syndrome, and
octreotide acetate is able to help by decreasing the release of damaging intestinal tumor cell
secretions. Octreotide also helps to reduce hypokalemia by correcting electrolyte imbalances.An excessive secretion of GH from the pituitary can cause the disorder known as acromegaly,
which is characterized by a progressive enlargement of the head, face, hands, feet, and thorax.
Inasmuch as octreotide acetate is able to decrease the secretion of GH from the pituitary, it is
used in treating patients with acromegaly who are unresponsive to previous pituitary radiation
therapy or surgery. It is used in the treatment of acromegaly, because it reduces the blood
levels of both GH and insulin-like growth factor-I (IGF-I). The long-acting repository form of
octreotide acetate also is used in treating acromegaly, carcinoid tumors, and VIPomas, but in
monthly depot injections.Octreotide for IV injection is used in the treatment of acute bleeding from esophageal varices.
Variceal bleeding occurs in about half the patients with cirrhosis of the liver and is responsible
for about one-third of deaths in these patients. Octreotide is a potent vasoconstrictor that
reduces portal and collateral blood flow by constricting visceral vessels, which leads to reduced
portal blood pressure and decreases the bleeding.
Veterinary Drugs and Treatments
Octreotide may be useful in the adjunctive treatment of hyperinsulinemia
in patients with insulinomas (especially dogs, ferrets).
Response is variable, presumably dependent on whether the tumor
cells have receptors for somatostatin. Octreotide may also be useful
in the diagnosis and symptomatic treatment of gastrinomas in dogs
or cats. It may be of use in the treatment of acute pancreatitis, but
more research is needed before it can be recommended for this use
in veterinary patients.
Mode of action
Octreotide acetate is a synthetic somatostatin analogue with similar pharmacologic effects to naturally occurring somatostatin, but with a prolonged duration of action. It inhibits pathologically increased secretion of growth hormone, thyroid stimulating hormone, and serotonin, insulin, glucagon, and other peptides produced within the gastro-entero-pancreatic endocrine system. Somatostatin is cell cycle phase-specific, mediating arrest at the G1- phase. Long acting somatostatin analogues have been shown to inhibit tumour growth.
Check Digit Verification of cas no
The CAS Registry Mumber 83150-76-9 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 8,3,1,5 and 0 respectively; the second part has 2 digits, 7 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 83150-76:
(7*8)+(6*3)+(5*1)+(4*5)+(3*0)+(2*7)+(1*6)=119
119 % 10 = 9
So 83150-76-9 is a valid CAS Registry Number.
InChI:InChI=1/C49H66N10O10S2.C2H4O2/c1-28(61)39(25-60)56-48(68)41-27-71-70-26-40(57-43(63)34(51)21-30-13-5-3-6-14-30)47(67)54-37(22-31-15-7-4-8-16-31)45(65)55-38(23-32-24-52-35-18-10-9-17-33(32)35)46(66)53-36(19-11-12-20-50)44(64)59-42(29(2)62)49(69)58-41;1-2(3)4/h3-10,13-18,24,28-29,34,36-42,52,60-62H,11-12,19-23,25-27,50-51H2,1-2H3,(H,53,66)(H,54,67)(H,55,65)(H,56,68)(H,57,63)(H,58,69)(H,59,64);1H3,(H,3,4)/t28-,29-,34-,36+,37+,38-,39-,40+,41+,42+;/m1./s1
83150-76-9Relevant articles and documents
Use of trichloroacetimidate linker in solid-phase peptide synthesis
Yan, Liang Zeng,Mayer, John P.
, p. 1161 - 1162 (2003)
A solid-phase method for the preparation of C-terminal amino-alcohol-containing peptides using activated Wang resin is presented. A diverse set of (fluorenylmethoxy)carbonyl (Fmoc) protected amino alcohols was found to load rapidly and efficiently. The synthetic utility of this approach was demonstrated through the direct synthesis of the peptide drug octreotide with excellent yield and purity. These results suggest that the use of trichloroacetimidate activated resins offers an attractive alternative in the preparation of this class of peptides.
METHOD FOR PRODUCTION OF OCTREOTIDE
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Paragraph 0060, (2016/10/08)
PROBLEM TO BE SOLVED: To provide a method for producing high-purity octreotide with high yields in a liquid phase synthesis method. SOLUTION: The present invention provides a method for producing octreotide or a salt thereof by using an acetal compound represented by formula (3) or a salt thereof as an intermediate, desorbing the amino protective group R1a, repeating condensation reaction with a protected amino acid and desorption of a protective group, and further performing oxidation reaction thereof. SELECTED DRAWING: None COPYRIGHT: (C)2016,JPOandINPIT
Electrophilic S-trifluoromethylation of cysteine side chains in α- and β-peptides: Isolation of trifluoromethylated sandostatin (octreotide) derivatives
Caponea, Stefania,Kieltschb, Iris,Floegela, Oliver,Lelaisa, Gerald,Togni, Antonio,Seebach, Dieter
body text, p. 2035 - 2056 (2009/02/08)
The new electrophilic trifluoromethylating 1-(trifluoromethyl)-benziodoxole reagents A and B (Scheme 1) have been used to selectively attach CF3 groups to the S-atom of cysteine side chains of α- and β-peptides (up to 13-residues-long; products 7-14). Other functional groups in the substrates (amino, amido, carbamate, carboxylate, hydroxy, phenyl) are not attacked by these soft reagents. Depending on the conditions, the indole ring of a Trp residue may also be trifluoromethylated (in the 2-position). The products are purified by chromatography, and identified by 1H-, 13C-, and 19F-NMR spectroscopy, by CD spectroscopy, and by high-resolution mass spectrometry. The CF3 groups, thus introduced, may be replaced by H (Na/NH3), an overall Cys/Ala conversion. The importance of trifluoromethylations in medicinal chemistry and possible applications of the method (spin-labelling, imaging, PET) are discussed.
