51110-01-1 Usage
Description
Somatostatin, also known as somatotropin release-inhibiting factor (SRIF), is a 14-amino acid oligopeptide hormone that was originally isolated from hypothalamic tissue. It is primarily involved in regulating the endocrine system by inhibiting the release of growth hormone (GH) from the pituitary gland. Additionally, somatostatin suppresses the release of insulin and glucagon, decreases cAMP levels and adenylate cyclase activity, and modulates calcium and potassium ion permeability in pituitary cells and the pancreas, respectively.
Uses
Used in Endocrinology:
Somatostatin is used as a therapeutic agent for regulating hormone release in the endocrine system. Its primary application is the inhibition of growth hormone (GH) release from the pituitary gland. It also plays a role in suppressing the secretion of insulin and glucagon, making it useful for managing conditions related to hormone imbalances.
Used in Pharmaceutical Research:
Somatostatin and its analogues, such as SOM230 and PT R3173, are used as research tools for studying the function and regulation of somatostatin receptor subtypes (sst1 to sst5). These analogues have shown selectivity for specific receptor subtypes and have potential applications in developing targeted therapies for various endocrine-related disorders.
Used in Diagnostic Imaging:
Somatostatin receptor scintigraphy (SRS) is a diagnostic imaging technique that utilizes radiolabeled somatostatin analogues to visualize tumors expressing somatostatin receptors. This method is particularly useful for detecting neuroendocrine tumors and other cancers that overexpress these receptors, aiding in the diagnosis and monitoring of disease progression.
Used in Oncology:
Somatostatin analogues, such as SOM230, have shown potential in the treatment of certain types of cancer by effectively decreasing plasma GH and insulin-like growth factor-1 (IGF-1) levels. This can help in controlling tumor growth and progression, as these growth factors are often involved in cancer development.
Discovery
This is a tetradecapeptide exerting a growth hormone
(GH) release-inhibiting activity. SS also has a large variety
of neuromodulatory and gastrointestinal actions, mostly as
an inhibitory hormone.?SS of 14 aa residues (SS-14) was first isolated from
ovine hypothalamic extracts by Roger Guillemin’s group
in 1973 and was originally named GH inhibiting factor. An N-terminally extended form of 28 aa residues (SS-28)
was isolated later from the porcine gut. SS cDNA that
encodes a precursor for SS-14 and SS-28, a product of
the SS1 gene (approved symbol SST), was first cloned
from the anglerfish pancreas in 1980. In this report,
another SS cDNA encoding a different precursor (formerly called SSII), a product of the SS3 gene, was also isolated. Subsequently, cDNAs and genes encoding SS
precursors have been identified in many animals by
molecular cloning and bioinformatic analyses, and so
far six paralogous genes (SS1, SS2, SS3, SS4, SS5, and
SS6) have been identified in vertebrates. Accordingly,
two SS-related peptides, cortistatin (CST)5 and
neuronostatin, have been identified.
Structure
SS-14 and SS-28 contain a disulfide bridge and have a
cyclic structure. CST, a product of the SS2/CST
gene, is 14–17 aa residues in length, depending on the
species, and contains the SS2 signature, a proline residue
at position 2. CST in placental mammals exhibits an
additional lysine residue at its C-terminal extremity. Neuronostatin is a 13-residue amidated peptide that is
flanked with the signal peptide of the SS1 precursor, and is an acyclic peptide.? The aa sequence of SS-14 is fully conserved in vertebrates. SS-28 in mammals that contains the SS-14 moiety
at its C-terminal shares 40%–66% sequence identity with
its counterparts in fish. Mr 1638 (SS-14), 3149 (SS-28). Soluble in water, acid,
and methanol. Stable in solution at -80°C for more than
a year. Plasma half-life is <3min.
Gene, mRNA, and precursor
The human preproSS gene (SS1), SST, location 3q28,
consists of two exons. Mammalian SS-14 and SS-28 are
derived from preproSS1 of 116 aa residues by specific
proprotein convertases (PCs) through tissue-specific
posttranslational processing. In vertebrates, six SS genes
have been identified, and all these paralogs are present in
teleost fish while only SS1 and SS2/CST are present in tetrapods. Phylogenetic and comparative genomic analyses
showed that whole-genome duplications, local duplications, and gene losses contribute to the divergent evolution of SS genes.
Clinical implications
Somatostatinoma is a malignant tumor that arises
from transformed D cells in the pancreatic islets or
duodenum. Somatostatinomas are associated with malabsorption, diabetes mellitus, steatorrhea, and cholelithiasis. In gastroenteropancreatic tumors, high levels of SS
receptor expression have been found, and specifically
designed analogs are used for tumor imaging and radiotherapy. SS deficiency causes persistent Helicobacter pylori
infection in the patient with chronic gastritis.
Receptors
SS receptors belong to the family of seventransmembrane-domain GPCRs. There are five subtypes
(sst1–sst5), and all these receptors bind to SS and CST with
high affinity.7 The structural and functional characteristics of these receptors in humans, including signal transduction pathways, agonists, and antagonists.
Biological functions
In the anterior pituitary, SS inhibits the
release of GH and thyroid-stimulating hormone (TSH).
Pulsatile GH secretion reflects the pulsatile release of both
SS and GHRH in a reciprocal fashion. In fish, SS-14
inhibits the release of GH, prolactin, and insulin. In the
brain, SS has a variety of neuromodulatory roles in learning, cognitive functions, locomotor activity, anxiety, and
depression. CST has physiological functions, such as
depression of neuronal activity and induction of slowwave sleep. Moreover, SS exerts inhibitory effects on
various gastrointestinal functions, including gastric acid
secretion, gastric emptying, intestinal motility, and
release of insulin, glucagon, and various gastrointestinal
hormones.
Regulation of synthesis and release
SS secretion in the gastrointestinal tract is regulated by
the autonomous nervous system and various gut regulatory peptides including gastrin, cholecystokinin (CCK),?and substance P. The synthesis and release of hypothalamic SS are regulated by GH, growth hormone-releasing
hormone (GHRH), and glucose.
Indications
Somatostatin (or somatotropin release–inhibiting factor
[SRIF]) occurs primarily as a 14–amino acid peptide,
although a 28–amino acid form also exists.As with
the other hypothalamic peptides, it is formed by proteolytic
cleavage of a larger precursor. Somatostatin, originally
isolated from the hypothalamus, is also in many
other locations, including the cerebral cortex, brainstem,
spinal cord, gut, urinary system, and skin.
Somatostatin inhibits the secretion of many substances
in addition to growth hormone.
Clinical Use
Somatostatin has a very brief half-life in serum and
is not useful clinically.An 8–amino acid analogue with 2
D-amino acids substituted for the naturally occurring
L-amino acids is more stable, and monthly injections of
a depot form of this analogue (octreotide, Sandostatin
LAR) have several uses. Long-acting octreotide is used
to treat acromegaly, as described earlier. It is also used
to counteract unpleasant effects caused by overproduction
of secreted bioactive substances produced by neuroendocrine
tumors, including hyperinsulinemia from
insulinomas and secretions from carcinoid tumors that
cause severe diarrhea. Octreotide may also control severe
diarrhea associated with AIDS that has not responded
to other treatments.
Clinical Use
Extensive SS analogs with improved pharmacokinetics, bioavailability, and receptor subtype selectivity have
been developed. These include nonpeptidergic analogs and octapeptides such as octreotide
and lanreotide. Octreotide and lanreotide are long-acting
sst2-preferring agonists, and are used for the treatment of
acromegaly, gastroenteropancreatic tumors, neuroendocrine tumors, and other gastrointestinal disorders such
as secretory diarrhea and gastrointestinal bleeding.
Side effects
Somatostatin analogues (SSA) are a common treatment for some forms of neuroendocrine tumours (NETs). Somatostatin analogues are usually well tolerated which means you may not have many side effects.The main side effects areLoss of appetiteFeeling sickFeeling bloatedStomach painFatigue (tiredness)Increased diarrhoea (this is rare)Soreness at the injection siteUncommon side effects include sinus bradycardia, asthenia, headache,pruritus, decreased libido, increased serum bilirubin, and constipation.Transient side effects, gastrointestinal discomfort and decreased glucose tolerance, usually last only a few weeks after initiation of therapy. The most significant side effect associated with prolonged use of octreotide is formation of gallstones resulting from reduced bile flow.
Check Digit Verification of cas no
The CAS Registry Mumber 51110-01-1 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 5,1,1,1 and 0 respectively; the second part has 2 digits, 0 and 1 respectively.
Calculate Digit Verification of CAS Registry Number 51110-01:
(7*5)+(6*1)+(5*1)+(4*1)+(3*0)+(2*0)+(1*1)=51
51 % 10 = 1
So 51110-01-1 is a valid CAS Registry Number.
InChI:InChI=1/C76H104N18O19S2/c1-41(79)64(100)82-37-61(99)83-58-39-114-115-40-59(76(112)113)92-72(108)57(38-95)91-75(111)63(43(3)97)94-71(107)54(33-46-23-11-6-12-24-46)90-74(110)62(42(2)96)93-66(102)51(28-16-18-30-78)84-69(105)55(34-47-36-81-49-26-14-13-25-48(47)49)88-68(104)53(32-45-21-9-5-10-22-45)86-67(103)52(31-44-19-7-4-8-20-44)87-70(106)56(35-60(80)98)89-65(101)50(85-73(58)109)27-15-17-29-77/h4-14,19-26,36,41-43,50-59,62-63,81,95-97H,15-18,27-35,37-40,77-79H2,1-3H3,(H2,80,98)(H,82,100)(H,83,99)(H,84,105)(H,85,109)(H,86,103)(H,87,106)(H,88,104)(H,89,101)(H,90,110)(H,91,111)(H,92,108)(H,93,102)(H,94,107)(H,112,113)
