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Identification
NamePasireotide
Accession NumberDB06663
TypeSmall Molecule
GroupsApproved
Description

Pasireotide is a synthetic long-acting cyclic hexapeptide with somatostatin-like activity. It is marketed as a diaspartate salt called Signifor®, which is used in the treatment of Cushing’s disease.

Structure
Thumb
Synonyms
cyclo((4R)-4-(2-Aminoethylcarbamoyloxy)-L-prolyl-L-phenylglycyl-D-tryptophyl-L-lysyl-4-O-benzyl-L-tyrosyl-L- phenylalanyl-)
Pasireotida
Pasireotidum
SOM 230
SOM-230
SOM230
External Identifiers
  • SOM230
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Signiforinjection.3 mg/mLsubcutaneousNovartis Pharmaceuticals Corporation2012-12-14Not applicableUs
Signiforsolution0.3 mgsubcutaneousNovartis Pharmaceuticals Canada Inc2013-11-26Not applicableCanada
Signiforinjection.9 mg/mLsubcutaneousNovartis Pharmaceuticals Corporation2012-12-14Not applicableUs
Signiforsolution0.9 mgsubcutaneousNovartis Pharmaceuticals Canada Inc2013-11-28Not applicableCanada
Signiforinjection.6 mg/mLsubcutaneousNovartis Pharmaceuticals Corporation2012-12-14Not applicableUs
Signiforsolution0.6 mgsubcutaneousNovartis Pharmaceuticals Canada Inc2013-11-26Not applicableCanada
Signifor LarkitNovartis Pharmaceuticals Corporation2014-12-15Not applicableUs
Signifor Larpowder for suspension; kit20 mgintramuscularNovartis Pharmaceuticals Canada Inc2016-01-28Not applicableCanada
Signifor LarkitNovartis Pharmaceuticals Corporation2014-12-15Not applicableUs
Signifor Larpowder for suspension; kit40 mgintramuscularNovartis Pharmaceuticals Canada Inc2015-08-04Not applicableCanada
Signifor LarkitNovartis Pharmaceuticals Corporation2014-12-15Not applicableUs
Signifor Larpowder for suspension; kit60 mgintramuscularNovartis Pharmaceuticals Canada Inc2015-08-04Not applicableCanada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Pasireotide diaspartate
Thumb
  • InChI Key: NEEFMPSSNFRRNC-HQUONIRXSA-N
  • Monoisotopic Mass: 1312.576439194
  • Average Mass: 1313.4116
DBSALT000134
Pasireotide pamoate
ThumbNot applicableDBSALT001332
Categories
UNII98H1T17066
CAS number396091-73-9
WeightAverage: 1047.2062
Monoisotopic: 1046.50142376
Chemical FormulaC58H66N10O9
InChI KeyInChIKey=VMZMNAABQBOLAK-DBILLSOUSA-N
InChI
InChI=1S/C58H66N10O9/c59-27-13-12-22-46-52(69)64-47(30-38-23-25-42(26-24-38)76-36-39-16-6-2-7-17-39)53(70)66-49(31-37-14-4-1-5-15-37)57(74)68-35-43(77-58(75)61-29-28-60)33-50(68)55(72)67-51(40-18-8-3-9-19-40)56(73)65-48(54(71)63-46)32-41-34-62-45-21-11-10-20-44(41)45/h1-11,14-21,23-26,34,43,46-51,62H,12-13,22,27-33,35-36,59-60H2,(H,61,75)(H,63,71)(H,64,69)(H,65,73)(H,66,70)(H,67,72)/t43-,46+,47+,48-,49+,50+,51+/m1/s1
IUPAC Name
(3S,6R,9S,12S,15S,19R,20aS)-9-(4-aminobutyl)-15-benzyl-12-{[4-(benzyloxy)phenyl]methyl}-6-(1H-indol-3-ylmethyl)-1,4,7,10,13,16-hexaoxo-3-phenyl-icosahydropyrrolo[1,2-a]1,4,7,10,13,16-hexaazacyclooctadecan-19-yl N-(2-aminoethyl)carbamate
SMILES
NCCCC[C@@H]1NC(=O)[C@@H](CC2=CNC3=C2C=CC=C3)NC(=O)[C@@H](NC(=O)[C@@H]2C[[email protected]](CN2C(=O)[[email protected]](CC2=CC=CC=C2)NC(=O)[[email protected]](CC2=CC=C(OCC3=CC=CC=C3)C=C2)NC1=O)OC(=O)NCCN)C1=CC=CC=C1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as cyclic peptides. These are compounds containing a cyclic moiety bearing a peptide backbone.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentCyclic peptides
Alternative Parents
Substituents
  • Cyclic alpha peptide
  • Macrolactam
  • Indole or derivatives
  • Indole
  • Phenol ether
  • Alkyl aryl ether
  • Benzenoid
  • Substituted pyrrole
  • Monocyclic benzene moiety
  • Heteroaromatic compound
  • Tertiary carboxylic acid amide
  • Pyrrolidine
  • Pyrrole
  • Tertiary amine
  • Secondary carboxylic acid amide
  • Lactam
  • Carboxamide group
  • Azacycle
  • Organoheterocyclic compound
  • Monocarboxylic acid or derivatives
  • Ether
  • Carboxylic acid amide
  • Hydrocarbon derivative
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Primary aliphatic amine
  • Carbonyl group
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationFor the treatment of Cushing’s disease, specifically for those patients whom pituitary surgery has not been curative or is not an option.
PharmacodynamicsSignifor® is an analogue of somatostatin that promotes reduced levels of cortisol secretion in Cushing's disease patients.
Mechanism of actionPasireotide activates a broad spectrum of somatostatin receptors, exhbiting a much higher binding affinity for somatostatin receptors 1, 3, and 5 than octreotide in vitro, as well as a comparable binding affinity for somatostatin receptor 2. The binding and activation of the somatostatin receptors causes inhibition of ACTH secretion and results in reduced cortisol secretion in Cushing's disease patients. Also this agent is more potent than somatostatin in inhibiting the release of human growth hormone (HGH), glucagon, and insulin.
Related Articles
AbsorptionThe peak plasma concentration of pasireotide occurs in 0.25-0.5 hours. After administration of single and multiple doses, there is dose-proportionoal increases in Cmax and AUC.
Volume of distribution

Pasireotide is widely distributed and has a volume of distribution of >100L.

Protein bindingPlasma protein binding is 88%.
Metabolism

Metabolism is minimal.

Route of eliminationPasireotide is eliminated mostly by hepatic clearance (biliary excretion)(about 48%) with some minor renal clearance (about 7.63%).
Half lifeThe half-life is 12 hours.
Clearance

The clearance in healthy patient is ~7.6 L/h and in Cushing’s disease patients is ~3.8 L/h.

ToxicityThe most common toxic effects observed are hyperglycemia, cholelithiasis, diarrhea, nausea, headache, abdominal pain, fatigue, and diabetes mellitus.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9926
Blood Brain Barrier-0.5389
Caco-2 permeable-0.8325
P-glycoprotein substrateSubstrate0.656
P-glycoprotein inhibitor INon-inhibitor0.6717
P-glycoprotein inhibitor IINon-inhibitor0.6843
Renal organic cation transporterNon-inhibitor0.777
CYP450 2C9 substrateNon-substrate0.8878
CYP450 2D6 substrateNon-substrate0.758
CYP450 3A4 substrateSubstrate0.521
CYP450 1A2 substrateNon-inhibitor0.7641
CYP450 2C9 inhibitorNon-inhibitor0.7676
CYP450 2D6 inhibitorNon-inhibitor0.8704
CYP450 2C19 inhibitorInhibitor0.5307
CYP450 3A4 inhibitorInhibitor0.575
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6561
Ames testNon AMES toxic0.7722
CarcinogenicityNon-carcinogens0.8568
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.4609 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8711
hERG inhibition (predictor II)Inhibitor0.7476
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Injectionsubcutaneous.3 mg/mL
Injectionsubcutaneous.6 mg/mL
Injectionsubcutaneous.9 mg/mL
Solutionsubcutaneous0.3 mg
Solutionsubcutaneous0.6 mg
Solutionsubcutaneous0.9 mg
Kit
Powder for suspension; kitintramuscular20 mg
Powder for suspension; kitintramuscular40 mg
Powder for suspension; kitintramuscular60 mg
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6225284 No1996-06-282016-06-28Us
US7473761 No2005-07-292025-07-29Us
US7759308 No2006-10-252026-10-25Us
US8299209 No2005-12-272025-12-27Us
US8822637 No2003-08-062023-08-06Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
water solubilitySoluble in water.From The Merck Index.
Predicted Properties
PropertyValueSource
Water Solubility0.00203 mg/mLALOGPS
logP3.03ALOGPS
logP2.68ChemAxon
logS-5.7ALOGPS
pKa (Strongest Acidic)9.09ChemAxon
pKa (Strongest Basic)10.43ChemAxon
Physiological Charge2ChemAxon
Hydrogen Acceptor Count10ChemAxon
Hydrogen Donor Count9ChemAxon
Polar Surface Area281.2 Å2ChemAxon
Rotatable Bond Count18ChemAxon
Refractivity286.66 m3·mol-1ChemAxon
Polarizability111.29 Å3ChemAxon
Number of Rings8ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

Bruns C, Lewis I, Briner U, Meno-Tetang G, Weckbecker G: SOM230: a novel somatostatin peptidomimetic with broad somatotropin release inhibiting factor (SRIF) receptor binding and a unique antisecretory profile. Eur J Endocrinol. 2002 May;146(5):707-16.

General References
  1. Weckbecker G, Briner U, Lewis I, Bruns C: SOM230: a new somatostatin peptidomimetic with potent inhibitory effects on the growth hormone/insulin-like growth factor-I axis in rats, primates, and dogs. Endocrinology. 2002 Oct;143(10):4123-30. [PubMed:12239124 ]
External Links
ATC CodesH01CB05
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (567 KB)
MSDSDownload (567 KB)
Interactions
Drug Interactions
Drug
AcetohexamideAcetohexamide may increase the hypoglycemic activities of Pasireotide.
Acetylsalicylic acidAcetylsalicylic acid may increase the hypoglycemic activities of Pasireotide.
AlogliptinAlogliptin may increase the hypoglycemic activities of Pasireotide.
BretyliumBretylium may increase the bradycardic activities of Pasireotide.
BromocriptineThe serum concentration of Bromocriptine can be increased when it is combined with Pasireotide.
CanagliflozinCanagliflozin may increase the hypoglycemic activities of Pasireotide.
CeritinibPasireotide may increase the bradycardic activities of Ceritinib.
ChlorpropamideChlorpropamide may increase the hypoglycemic activities of Pasireotide.
CitalopramPasireotide may increase the QTc-prolonging activities of Citalopram.
CodeineThe metabolism of Codeine can be decreased when combined with Pasireotide.
CyclosporineThe serum concentration of Cyclosporine can be decreased when it is combined with Pasireotide.
DihydrotestosteroneDihydrotestosterone may increase the hypoglycemic activities of Pasireotide.
DofetilidePasireotide may increase the QTc-prolonging activities of Dofetilide.
EsmololEsmolol may increase the bradycardic activities of Pasireotide.
GliclazideGliclazide may increase the hypoglycemic activities of Pasireotide.
GlimepirideGlimepiride may increase the hypoglycemic activities of Pasireotide.
GliquidoneGliquidone may increase the hypoglycemic activities of Pasireotide.
GlyburideGlyburide may increase the hypoglycemic activities of Pasireotide.
GoserelinPasireotide may increase the QTc-prolonging activities of Goserelin.
Insulin AspartInsulin Aspart may increase the hypoglycemic activities of Pasireotide.
Insulin DetemirInsulin Detemir may increase the hypoglycemic activities of Pasireotide.
Insulin GlargineInsulin Glargine may increase the hypoglycemic activities of Pasireotide.
Insulin GlulisineInsulin Glulisine may increase the hypoglycemic activities of Pasireotide.
Insulin HumanInsulin Regular may increase the hypoglycemic activities of Pasireotide.
Insulin LisproInsulin Lispro may increase the hypoglycemic activities of Pasireotide.
IvabradinePasireotide may increase the bradycardic activities of Ivabradine.
LacosamidePasireotide may increase the atrioventricular blocking (AV block) activities of Lacosamide.
LeuprolidePasireotide may increase the QTc-prolonging activities of Leuprolide.
LinagliptinLinagliptin may increase the hypoglycemic activities of Pasireotide.
MetforminMetformin may increase the hypoglycemic activities of Pasireotide.
MifepristoneMifepristone may increase the QTc-prolonging activities of Pasireotide.
OctreotideOctreotide may increase the bradycardic activities of Pasireotide.
OxandroloneOxandrolone may increase the hypoglycemic activities of Pasireotide.
ParoxetineParoxetine may increase the hypoglycemic activities of Pasireotide.
PegvisomantThe risk or severity of adverse effects can be increased when Pasireotide is combined with Pegvisomant.
PhenelzinePhenelzine may increase the hypoglycemic activities of Pasireotide.
RepaglinideRepaglinide may increase the hypoglycemic activities of Pasireotide.
RuxolitinibRuxolitinib may increase the bradycardic activities of Pasireotide.
SaxagliptinSaxagliptin may increase the hypoglycemic activities of Pasireotide.
SparfloxacinSparfloxacin may increase the hypoglycemic activities of Pasireotide.
TestosteroneTestosterone may increase the hypoglycemic activities of Pasireotide.
TofacitinibTofacitinib may increase the bradycardic activities of Pasireotide.
TolbutamideTolbutamide may increase the hypoglycemic activities of Pasireotide.
TranylcypromineTranylcypromine may increase the hypoglycemic activities of Pasireotide.
VildagliptinVildagliptin may increase the hypoglycemic activities of Pasireotide.
Food Interactions
  • Since Signifor® is administered subcutaneously, food has no effect.

Targets

Kind
Protein
Organism
Human
Pharmacological action
unknown
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 stimulates phosphotyrosine phosphatase and Na(+)/H(+) exchanger via pertussis toxin insensitive G proteins.
Gene Name:
SSTR1
Uniprot ID:
P30872
Molecular Weight:
42685.77 Da
References
  1. Zatelli MC, Piccin D, Vignali C, Tagliati F, Ambrosio MR, Bondanelli M, Cimino V, Bianchi A, Schmid HA, Scanarini M, Pontecorvi A, De Marinis L, Maira G, degli Uberti EC: Pasireotide, a multiple somatostatin receptor subtypes ligand, reduces cell viability in non-functioning pituitary adenomas by inhibiting vascular endothelial growth factor secretion. Endocr Relat Cancer. 2007 Mar;14(1):91-102. [PubMed:17395978 ]
  2. Bruns C, Lewis I, Briner U, Meno-Tetang G, Weckbecker G: SOM230: a novel somatostatin peptidomimetic with broad somatotropin release inhibiting factor (SRIF) receptor binding and a unique antisecretory profile. Eur J Endocrinol. 2002 May;146(5):707-16. [PubMed:11980628 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
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 PLC via pertussis toxin insensitive as well as sensitive G proteins. Inhibits calcium entry by suppressing voltage-dependent calcium channels. Acts as the functionally dominant somatostatin receptor i...
Gene Name:
SSTR2
Uniprot ID:
P30874
Molecular Weight:
41332.37 Da
References
  1. Zatelli MC, Piccin D, Vignali C, Tagliati F, Ambrosio MR, Bondanelli M, Cimino V, Bianchi A, Schmid HA, Scanarini M, Pontecorvi A, De Marinis L, Maira G, degli Uberti EC: Pasireotide, a multiple somatostatin receptor subtypes ligand, reduces cell viability in non-functioning pituitary adenomas by inhibiting vascular endothelial growth factor secretion. Endocr Relat Cancer. 2007 Mar;14(1):91-102. [PubMed:17395978 ]
  2. Bruns C, Lewis I, Briner U, Meno-Tetang G, Weckbecker G: SOM230: a novel somatostatin peptidomimetic with broad somatotropin release inhibiting factor (SRIF) receptor binding and a unique antisecretory profile. Eur J Endocrinol. 2002 May;146(5):707-16. [PubMed:11980628 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
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
Molecular Weight:
45846.995 Da
References
  1. Zatelli MC, Piccin D, Vignali C, Tagliati F, Ambrosio MR, Bondanelli M, Cimino V, Bianchi A, Schmid HA, Scanarini M, Pontecorvi A, De Marinis L, Maira G, degli Uberti EC: Pasireotide, a multiple somatostatin receptor subtypes ligand, reduces cell viability in non-functioning pituitary adenomas by inhibiting vascular endothelial growth factor secretion. Endocr Relat Cancer. 2007 Mar;14(1):91-102. [PubMed:17395978 ]
  2. Bruns C, Lewis I, Briner U, Meno-Tetang G, Weckbecker G: SOM230: a novel somatostatin peptidomimetic with broad somatotropin release inhibiting factor (SRIF) receptor binding and a unique antisecretory profile. Eur J Endocrinol. 2002 May;146(5):707-16. [PubMed:11980628 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
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 activity of SSTR2 following heterodimerization.
Gene Name:
SSTR5
Uniprot ID:
P35346
Molecular Weight:
39201.925 Da
References
  1. Zatelli MC, Piccin D, Vignali C, Tagliati F, Ambrosio MR, Bondanelli M, Cimino V, Bianchi A, Schmid HA, Scanarini M, Pontecorvi A, De Marinis L, Maira G, degli Uberti EC: Pasireotide, a multiple somatostatin receptor subtypes ligand, reduces cell viability in non-functioning pituitary adenomas by inhibiting vascular endothelial growth factor secretion. Endocr Relat Cancer. 2007 Mar;14(1):91-102. [PubMed:17395978 ]
  2. Bruns C, Lewis I, Briner U, Meno-Tetang G, Weckbecker G: SOM230: a novel somatostatin peptidomimetic with broad somatotropin release inhibiting factor (SRIF) receptor binding and a unique antisecretory profile. Eur J Endocrinol. 2002 May;146(5):707-16. [PubMed:11980628 ]
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Drug created on March 19, 2008 10:46 / Updated on August 24, 2016 01:53