Identification

Name
Somatostatin
Accession Number
DB09099
Type
Small Molecule
Groups
Approved, Investigational
Description

Somatostatin, also known as growth hormone-inhibiting hormone, is a naturally-occurring peptide hormone of 14 or 28 amino acid residues [9] that regulates the endocrine system. It is secreted by the D cells of the islets to inhibit the release of insulin and glucagon, and is also generated in the hypothalamus, where it inhibits the release of growth hormone and thyroid-stimulating hormones from the anterior pituitary [9]. Somatostatin is initially secreted as a 116 amino acid precursor, preprosomatostatin, which undergoes endoproteolytic cleavage to prosomastatin. Prosomastatin is further process into two active forms, somatostatin-14 (SST-14) and somatostatin-28 (SST-28), an extended SST-14 sequence to the N-terminus [1]. The actions of somatostatin are mediated via signalling pathways of G protein-coupled somatostatin receptors.

Antineoplastic effects and potential uses of somatostatin on various tumours, including pituitary adenomas, GEP-NETs, paragangliomas, carcinoids, breast cancers, malignant lymphoma and small-cell lung cancers, have been extensively investigated [1]. Somatostatin has been used in the clinical setting for the diagnosis of acromegaly and gastrointestinal tract tumours. Its analogues have been developed to achieve more favourable kinetics for efficiency use in the management of acute conditions, such as esophageal varices. Octreotide is a long-acting analogue of somatostatin that inhibits the release of a number of hormones, and is clinically used to relieve symptoms of uncommon gastroenteropancreatic endocrine tumours, as well as treat acromegaly [9].

Structure
Thumb
Synonyms
  • Somatostatina
  • Somatostatine
  • Somatostatinum
  • Synthetic growth hormone release-inhibiting hormone
  • Synthetic somatostatin-14
External IDs
SRIF-14
Product Ingredients
IngredientUNIICASInChI Key
Somatostatin acetateF6R2N217HS54472-66-1Not applicable
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Stilamin - Pws IV 3mg/ampPowder, for solution3 mgIntravenousEmd Serono, A Division Of Emd Inc., Canada1997-11-102014-12-12Canada
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Stilamin - Pws Liq IVSomatostatin (250 mcg) + Sodium Chloride (9 mg)Liquid; Powder, for solutionIntravenousEmd Serono, A Division Of Emd Inc., Canada1997-09-162014-12-12Canada
Categories
UNII
6E20216Q0L
CAS number
38916-34-6
Weight
Average: 1637.9
Monoisotopic: 1636.716655549
Chemical Formula
C76H104N18O19S2
InChI Key
NHXLMOGPVYXJNR-ATOGVRKGSA-N
InChI
InChI=1S/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)/t41-,42+,43+,50-,51-,52-,53-,54-,55-,56-,57-,58-,59-,62-,63-/m0/s1
IUPAC Name
(4R,7S,10S,13S,16S,19S,22S,25S,28S,31S,34S,37R)-19,34-bis(4-aminobutyl)-37-{2-[(2S)-2-aminopropanamido]acetamido}-13,25,28-tribenzyl-31-(carbamoylmethyl)-10,16-bis[(1R)-1-hydroxyethyl]-7-(hydroxymethyl)-22-[(1H-indol-3-yl)methyl]-6,9,12,15,18,21,24,27,30,33,36-undecaoxo-1,2-dithia-5,8,11,14,17,20,23,26,29,32,35-undecaazacyclooctatriacontane-4-carboxylic acid
SMILES
C[C@@H](O)[C@@H]1NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC2=CNC3=C2C=CC=C3)NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CSSC[C@H](NC(=O)[C@H](CO)NC1=O)C(O)=O)NC(=O)CNC(=O)[C@H](C)N)[C@@H](C)O

Pharmacology

Indication

For the symptomatic treatment of acute bleeding from esophageal varices. Other treatment options for long-term management of the condition may be considered if necessary, once initial control has been established.

Pharmacodynamics

Somatostatin is an endogenous peptide hormone that is secreted by the central nervous system, gastrointestinal tract, retina, peripheral neurons and pancreatic D cells of the islets of Langerhans. It exhibits several biological roles but predominantly exerts an inhibitory effect on secretion of other hormones and transmitters [1]. While distribution of two active isoforms of somatostatin is similar, SST-14 is more predominant in the enteric neurons and peripheral nerves whereas SST-28 is more prominent in the retina and intestinal mucosal cells [1].

Anterior pituitary gland and brain: It inhibits the release of growth hormones and thyroid-stimulating hormones, such as thyroid stimulating hormone (TSH) and thyrotrophin, from the anterior pituitary while inhibiting the release of dopamine from the midbrain, norepinephrine, TRH and corticotrophin-releasing hormone in the brain [1].

Pancreas: In the pancreas, somatostatin reduces the secretion of glucagon and insulin as well as bicarbonate ions and other enzymes [1, 9].

Thyroid gland: Somatosatin reduces secretion of T3, T4, and calcitonin [1]. Somatostatin regulates the thyroid function by reducing basal TSH release [9].

Gastrointestinal tract: It attenuates the release of most gastrointestinal hormones such as gastrin, secretin, motilin, gastric acid, enteroglucagon, cholecystokinin (CCK), vasoactive intestinal peptide (VIP), gastric inhibitory polypeptide (GIP), intrinsic factor, pepsin, neurotensin, as well as bile secretion and colonic fluid secretion [1].

Adrenal gland: It inhibits angiotensin II-stimulated aldosterone secretion and acetylcholine-induced medullary catecholamine secretion [1].

Eye/retina: Somatostatin inhibits the production of vascular endothelial growth factor [1].

Inflammatory cells and sensory nerves: The expression of somatostatin has been found in inflammatory cells such as lymphocytes, monocytes, macrophages and endothelial cells to act as an autocrine or paracrine regulator in local immune responses. Findings suggest that somatostatin may play a role in exerting local and systemic anti-inflammatory and antinociceptive effects [1]. On primary afferent neurons, somatostatin reduces the responses to thermal stimulation in C-mechanoheat sensitive fibers in a dose-dependent fashion and reduces the responses of C-mechanoheat fibers to bradykinin-induced excitation and sensitization to heat [6]. Somatostatin is reported to elicit an analgesic effect when applied intrathecally; there is evidence supporting that similar effects may occur when systemically used to treat endocrine disorders [9].

Somatostatin is thought to reduce bleeding from esophageal varices by causing splanchnic vasoconstriction [2]. Somatostatin elicits anti-neoplastic actions on various tumours via direct or indirect effects, or a combination of both [4].

Mechanism of action

Somatostatin binds to 5 subtypes of somatostatin receptors (SSTRs), which are all Gi-protein-coupled transmembrane receptors that inhibits adenylyl cyclase upon activation [1]. By inhibiting intracellular cyclic AMP and Ca2+ and by a receptor-linked distal effect on exocytosis, SSTRs block cell secretion [3]. The common pathway shared by the receptors involve the activation of phosphotyrosine phosphatase (PTP), and modulation of mitogen-activated protein kinase (MAPK) [3]. With the exception of SSTR3, activation of SSTRs lead to activation of voltage-gated potassium channels accompanied by increased K+ currents. This result in membrane hyperpolarization and inhibits depolarization-induced Ca2+ influx through voltage-sensitive Ca2+ channels [1]. Depending on the receptor subtype, signalling cascades involve activation of other downstream targets such as Na+/H+ exchanger, Rho GTPase, and nitric oxide synthase (NOS) [1]. SSTRs 1 to 4 bind both somatostatin isoforms with equal nanomolar binding affinity whereas SSTR5 exhibits a 5- to 10-fold higher binding affinity for SST-28 [1].

Effects of SSTR1: Upon biding of somatostatin and activation, SSTR1 mediates an antisecretory effect on growth hormone, prolactin and calcitonin [1].

Effects of SSTR2: SSTR2 subtype dominates in endocrine tissues. By binding to SST2 receptors, somatostatin exerts paracrine inhibitory actions on gastrin release from G cells, histamine release from ECL cells, and directly on parietal cell acid output [9]. SSTR2 receptor signalling cascades also inhibit the secretion of growth hormone and that of adrenocorticotropin, glucagon, insulin, and interferon-γ [1].

Effects of SSTR3: Activation of these receptors lead to reduction in cell proliferation [1]. SSTR3 triggers PTP-dependent cell apoptosis accompanied by activation of p53 and the pro-apoptotic protein Bax [3]. A study of the matrigel sponge assay suggests that through SSTR3-mediated inhibition of both NOS and MAPK activities may lead to the antitumor effects of somatostatin in inhibiting tumor angiogenesis [8].

Effects of SSTR4: The functions of SSTR4 remain largely unknown [1].

Effects of SSTR5: Like SSTR2, SSTR5 subtype also predominates in endocrine tissues. Upon activation, SSTR5 signalling cascades exert an inhibitory action on growth hormone, adrenocorticotropin, insulin, and glucagon-like peptide-1 as well as the secretion of amylase [1].

The presence of somatostatin receptors has been identified in most neuroendocrine tumours, endocrine gastroenteropancreatic (GEP) tumors, paragangliomas, pheochromocytomas, medullary thyroid carcinomas (MTC) and small cell lung carcinomas [7]. The antitumor effects of somatostatin were also effective in various malignant lymphomas and breast tumours [7]. Gastrointestinal hormones, such as gastrin, secretin, and cholecystokinin (CCK), as well as growth hormones and growth factors are thought to be elevated in gastrointestinal tract and neuroendocrine tumours and are inhibited by somatostatin [4]. In vitro, somatostatin inhibited epidermal growth factor (EGF)-induced DNA synthesis and replication following which suggest that somatostatin may have direct anti-proliferative effects via SSTR signalling [4]. Acromegaly is characterized as the endocrine disorder caused by a functioning tumour of cells that secrete growth hormone from the anterior pituitary [9]. Somatostatin analogue therapies serve to normalize the elevated levels of GH and insulin-like growth factor 1 (IGF-1) and attenuate tumour growth.

In the vascular system this likely produces vasoconstriction by inhibiting adenylate cyclase leading to a lowering the concentration of cyclic adenosine monophosphate in the endothelial cells which ultimately blocks vasodilation through this pathway. This vasoconstriction is though the be responsible for reducing blood flow to the esophageal tissues and so reduces bleeding from esophageal varices [2].

Somatostatin mediates an analgesic activity by reducing vascular and nociceptive components of inflammation [6]. Studies indicate that somatostatin may be present in nociceptive DRG neurons with C-fibers and primary afferent neurons to inhibit the release of transmitters at the presynaptic junctions of the sensory-efferent nerve terminals [1]. Exogenous somatostatin has shown to inhibit the release of Substance P from central and peripheral nerve ending [1].

TargetActionsOrganism
ASomatostatin receptor type 1
agonist
Human
ASomatostatin receptor type 2
agonist
Human
ASomatostatin receptor type 3
agonist
Human
ASomatostatin receptor type 4
agonist
Human
ASomatostatin receptor type 5
agonist
Human
Absorption

This pharmacokinetic data is irrelevant.

Volume of distribution

This pharmacokinetic data is irrelevant.

Protein binding

This pharmacokinetic data is irrelevant.

Metabolism

Somatostatin is rapidly degraded by peptidase enzymes present in cells and plasma [1].

Route of elimination

As a polypeptide chain, somatostatin is primarily eliminated via metabolism by peptidase enzymes [1].

Half life

The half-life of endogenous somatostatin is 1-3 minutes due to rapid degradation by peptidase enzymes present in the plasma and tissues [1].

Clearance

Following intravenous administration of 3H-labeld endogenous somatostatin, the total body clearance was approximately 50 mL/min [5]. In man, the value was calculated to be as high as 3000 mL/minutes, which is greatly exceeds the hepatic blood flow. This suggests that rapid enzymatic breakdown in the circulation and other tissues serves as a critical route of elimination [5].

Toxicity

Data is not available.

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AcetaminophenThe serum concentration of Somatostatin can be increased when it is combined with Acetaminophen.
AlbendazoleThe serum concentration of Somatostatin can be increased when it is combined with Albendazole.
AlclometasoneThe metabolism of Alclometasone can be decreased when combined with Somatostatin.
AlfentanilThe metabolism of Alfentanil can be decreased when combined with Somatostatin.
AlfuzosinThe metabolism of Alfuzosin can be decreased when combined with Somatostatin.
AlmotriptanThe metabolism of Almotriptan can be decreased when combined with Somatostatin.
AlosetronThe metabolism of Alosetron can be decreased when combined with Somatostatin.
AlprazolamThe metabolism of Alprazolam can be decreased when combined with Somatostatin.
AmcinonideThe metabolism of Amcinonide can be decreased when combined with Somatostatin.
AmiodaroneThe serum concentration of Somatostatin can be increased when it is combined with Amiodarone.
Food Interactions
Not Available

References

General References
  1. Rai U, Thrimawithana TR, Valery C, Young SA: Therapeutic uses of somatostatin and its analogues: Current view and potential applications. Pharmacol Ther. 2015 Aug;152:98-110. doi: 10.1016/j.pharmthera.2015.05.007. Epub 2015 May 5. [PubMed:25956467]
  2. Hanisch E, Doertenbach J, Usadel KH: Somatostatin in acute bleeding oesophageal varices. Pharmacology and rationale for use. Drugs. 1992;44 Suppl 2:24-35; discussion 70-2. [PubMed:1385068]
  3. Patel YC: Somatostatin and its receptor family. Front Neuroendocrinol. 1999 Jul;20(3):157-98. [PubMed:10433861]
  4. Lamberts SW, de Herder WW, Hofland LJ: Somatostatin analogs in the diagnosis and treatment of cancer. Trends Endocrinol Metab. 2002 Dec;13(10):451-7. [PubMed:12431842]
  5. Marbach P, Briner U, Lemaire M, Schweitzer A, Terasaki T: From somatostatin to sandostatin: pharmacodynamics and pharmacokinetics. Metabolism. 1992 Sep;41(9 Suppl 2):7-10. [PubMed:1355590]
  6. Carlton SM, Du J, Davidson E, Zhou S, Coggeshall RE: Somatostatin receptors on peripheral primary afferent terminals: inhibition of sensitized nociceptors. Pain. 2001 Feb 15;90(3):233-44. [PubMed:11207395]
  7. Reubi JC, Laissue J, Krenning E, Lamberts SW: Somatostatin receptors in human cancer: incidence, characteristics, functional correlates and clinical implications. J Steroid Biochem Mol Biol. 1992 Sep;43(1-3):27-35. [PubMed:1356016]
  8. Florio T, Morini M, Villa V, Arena S, Corsaro A, Thellung S, Culler MD, Pfeffer U, Noonan DM, Schettini G, Albini A: Somatostatin inhibits tumor angiogenesis and growth via somatostatin receptor-3-mediated regulation of endothelial nitric oxide synthase and mitogen-activated protein kinase activities. Endocrinology. 2003 Apr;144(4):1574-84. doi: 10.1210/en.2002-220949. [PubMed:12639942]
  9. 29, 30, 32, 33, 41, . (2012). In Rang and Dale's Pharmacology (7th ed., pp. 362, 372, 377, 394-395, 412, 522). Edinburgh: Elsevier/Churchill Livingstone. [ISBN:978-0-7020-3471-8]
External Links
KEGG Drug
D07431
PubChem Compound
16129681
PubChem Substance
310265025
ChemSpider
17286507
BindingDB
81767
ChEBI
64628
ChEMBL
CHEMBL1823872
Wikipedia
Somatostatin
ATC Codes
H01CB01 — Somatostatin
MSDS
Download (21.9 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableHealthy Volunteers1
1CompletedBasic ScienceNormal Healthy Volunteers1
1CompletedTreatmentLiver Transplant With Clinically Significant Portal Hypertension1
1Not Yet RecruitingTreatmentProstatic Neoplasms1
3CompletedTreatmentAutosomal Dominant Polycystic Kidney Disease (ADPKD)1
3CompletedTreatmentGallbladder Neoplasms1
3CompletedTreatmentHepatocellular,Carcinoma1
3RecruitingPreventionHepatocellular,Carcinoma1
3RecruitingTreatmentHepatic Failure1
3RecruitingTreatmentPancreatic Surgery1
3Unknown StatusPreventionAcute Pancreatitis (AP)1
4CompletedTreatmentGastric Cancer After D2 Lymph Node Dissection1
4CompletedTreatmentHaemorrhage / Varices, Esophageal1
4CompletedTreatmentSmall intestinal obstruction1
4CompletedTreatmentVariceal Bleeding, Cirrhosis1
4CompletedTreatmentVasoconstrictor Choice on Acute Variceal Bleeding1
4Unknown StatusTreatmentPancreatitis,Acute Necrotizing1
Not AvailableActive Not RecruitingBasic ScienceNormal Cellular Metabolism1
Not AvailableCompletedNot AvailableDiabetes, Diabetes Mellitus Type 1 / Hypoglycemia Unawareness1
Not AvailableCompletedBasic ScienceAcromegaly / Diabetes Mellitus (DM) / Growth Hormone Deficiency (GHD)1
Not AvailableCompletedOtherDiabetes, Diabetes Mellitus Type 11
Not AvailableCompletedTreatmentAcute Bleeding Esophageal Varices / Liver Cirrhosis / Portal Hypertension1
Not AvailableCompletedTreatmentFatty Acids, Nonesterified / Glomerular Filtration Rate (GFR) / Renal Circulation / Renal Plasma Flow1
Not AvailableRecruitingNot AvailableHemorrhage / Liver Cirrhosis / Portal Vein / Thrombosis, Venous / Varicosities of the great saphenous vein1
Not AvailableRecruitingDiagnosticDumping Syndrome / Gastric Resection / Hypoglycemia / Oesophagectomy1
Not AvailableUnknown StatusNot AvailableEsophageal and Gastric Varices / Hemorrhage / Liver Cirrhosis1
Not AvailableUnknown StatusBasic ScienceEsophageal Varices Secondary to Cirrhosis of Liver1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Powder, for solutionIntravenous3 mg
Liquid; powder, for solutionIntravenous
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0205 mg/mLALOGPS
logP-1.8ALOGPS
logP-8.2ChemAxon
logS-4.9ALOGPS
pKa (Strongest Acidic)2.88ChemAxon
pKa (Strongest Basic)10.47ChemAxon
Physiological Charge2ChemAxon
Hydrogen Acceptor Count22ChemAxon
Hydrogen Donor Count22ChemAxon
Polar Surface Area613.23 Å2ChemAxon
Rotatable Bond Count26ChemAxon
Refractivity420.26 m3·mol-1ChemAxon
Polarizability165.8 Å3ChemAxon
Number of Rings6ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Classification
Not classified

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Somatostatin receptor activity
Specific Function
Receptor for somatostatin with higher affinity for somatostatin-14 than -28. This receptor is coupled via pertussis toxin sensitive G proteins to inhibition of adenylyl cyclase. In addition it stim...
Gene Name
SSTR1
Uniprot ID
P30872
Uniprot Name
Somatostatin receptor type 1
Molecular Weight
42685.77 Da
References
  1. Rai U, Thrimawithana TR, Valery C, Young SA: Therapeutic uses of somatostatin and its analogues: Current view and potential applications. Pharmacol Ther. 2015 Aug;152:98-110. doi: 10.1016/j.pharmthera.2015.05.007. Epub 2015 May 5. [PubMed:25956467]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Somatostatin receptor activity
Specific Function
Receptor for somatostatin-14 and -28. This receptor is coupled via pertussis toxin sensitive G proteins to inhibition of adenylyl cyclase. In addition it stimulates phosphotyrosine phosphatase and ...
Gene Name
SSTR2
Uniprot ID
P30874
Uniprot Name
Somatostatin receptor type 2
Molecular Weight
41332.37 Da
References
  1. Rai U, Thrimawithana TR, Valery C, Young SA: Therapeutic uses of somatostatin and its analogues: Current view and potential applications. Pharmacol Ther. 2015 Aug;152:98-110. doi: 10.1016/j.pharmthera.2015.05.007. Epub 2015 May 5. [PubMed:25956467]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Somatostatin receptor activity
Specific Function
Receptor for somatostatin-14 and -28. This receptor is coupled via pertussis toxin sensitive G proteins to inhibition of adenylyl cyclase.
Gene Name
SSTR3
Uniprot ID
P32745
Uniprot Name
Somatostatin receptor type 3
Molecular Weight
45846.995 Da
References
  1. Rai U, Thrimawithana TR, Valery C, Young SA: Therapeutic uses of somatostatin and its analogues: Current view and potential applications. Pharmacol Ther. 2015 Aug;152:98-110. doi: 10.1016/j.pharmthera.2015.05.007. Epub 2015 May 5. [PubMed:25956467]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Receptor for somatostatin-14. The activity of this receptor is mediated by G proteins which inhibits adenylyl cyclase. It is functionally coupled not only to inhibition of adenylate cyclase, but also to activation of both arachidonate release and mitogen-activated protein (MAP) kinase cascade. Mediates antiproliferative action of somatostatin in tumor cells.
Specific Function
Neuropeptide binding
Gene Name
SSTR4
Uniprot ID
P31391
Uniprot Name
Somatostatin receptor type 4
Molecular Weight
42002.245 Da
References
  1. Rai U, Thrimawithana TR, Valery C, Young SA: Therapeutic uses of somatostatin and its analogues: Current view and potential applications. Pharmacol Ther. 2015 Aug;152:98-110. doi: 10.1016/j.pharmthera.2015.05.007. Epub 2015 May 5. [PubMed:25956467]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Somatostatin receptor activity
Specific Function
Receptor for somatostatin 28 and to a lesser extent for somatostatin-14. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase. Increases cell growth inhibition act...
Gene Name
SSTR5
Uniprot ID
P35346
Uniprot Name
Somatostatin receptor type 5
Molecular Weight
39201.925 Da
References
  1. Rai U, Thrimawithana TR, Valery C, Young SA: Therapeutic uses of somatostatin and its analogues: Current view and potential applications. Pharmacol Ther. 2015 Aug;152:98-110. doi: 10.1016/j.pharmthera.2015.05.007. Epub 2015 May 5. [PubMed:25956467]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Uchiyama-Kokubu N, Naito M, Nakajima M, Tsuruo T: Transport of somatostatin and substance P by human P-glycoprotein. FEBS Lett. 2004 Sep 10;574(1-3):55-61. doi: 10.1016/j.febslet.2004.07.084. [PubMed:15358539]

Drug created on September 16, 2015 14:56 / Updated on October 01, 2018 16:34