Identification

Name
Pasireotide
Accession Number
DB06663
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.

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 1047.2062
Monoisotopic: 1046.50142376
Chemical Formula
C58H66N10O9
Synonyms
  • cyclo((4R)-4-(2-aminoethylcarbamoyloxy)-L-prolyl-L-phenylglycyl-D-tryptophyl-L-lysyl-4-O-benzyl-L-tyrosyl-L- phenylalanyl-)
  • Pasireotida
  • Pasiréotide
  • Pasireotide
  • Pasireotidum
External IDs
  • SOM 230
  • SOM-230
  • SOM230

Pharmacology

Indication

For the treatment of Cushing’s disease, specifically for those patients whom pituitary surgery has not been curative or is not an option.

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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Pharmacodynamics

Signifor® is an analogue of somatostatin that promotes reduced levels of cortisol secretion in Cushing's disease patients.

Mechanism of action

Pasireotide 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.

TargetActionsOrganism
USomatostatin receptor type 1Not AvailableHumans
USomatostatin receptor type 2Not AvailableHumans
USomatostatin receptor type 3Not AvailableHumans
USomatostatin receptor type 5Not AvailableHumans
Absorption

The 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 binding

Plasma protein binding is 88%.

Metabolism

Metabolism is minimal.

Route of elimination

Pasireotide is eliminated mostly by hepatic clearance (biliary excretion)(about 48%) with some minor renal clearance (about 7.63%).

Half-life

The 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.

Adverse Effects
Learn about our commercial Adverse Effects data.
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Toxicity

The most common toxic effects observed are hyperglycemia, cholelithiasis, diarrhea, nausea, headache, abdominal pain, fatigue, and diabetes mellitus.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbemaciclibThe metabolism of Abemaciclib can be decreased when combined with Pasireotide.
AcalabrutinibThe metabolism of Acalabrutinib can be decreased when combined with Pasireotide.
AcarboseThe therapeutic efficacy of Acarbose can be decreased when used in combination with Pasireotide.
AcebutololThe risk or severity of QTc prolongation can be increased when Pasireotide is combined with Acebutolol.
AcenocoumarolThe serum concentration of Acenocoumarol can be increased when it is combined with Pasireotide.
AcetohexamideThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Pasireotide.
AcrivastineThe risk or severity of QTc prolongation can be increased when Pasireotide is combined with Acrivastine.
AdenosineThe risk or severity of QTc prolongation can be increased when Pasireotide is combined with Adenosine.
AjmalineThe risk or severity of QTc prolongation can be increased when Ajmaline is combined with Pasireotide.
AlbendazoleThe metabolism of Albendazole can be decreased when combined with Pasireotide.
Additional Data Available
  • Extended Description
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    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity
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    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level
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  • Action
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Food Interactions
No interactions found.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Pasireotide acetate662X0VFR9L396091-76-2WFKFNBBHVLMWQH-QKXVGOHISA-N
Pasireotide diaspartateI4P76SY3N4820232-50-6NEEFMPSSNFRRNC-HQUONIRXSA-N
Pasireotide pamoate04F55A7UZ3396091-79-5HSXBEUMRBMAVDP-QKXVGOHISA-N
International/Other Brands
Signifor / Signifor LAR
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
SigniforInjection, powder, for suspension60 mgIntramuscularNovartis Europharm Limited2012-04-24Not applicableEU flag
SigniforInjection0.3 mg/1mLSubcutaneousNovartis Pharmaceuticals Corporation2012-12-14Not applicableUS flag
SigniforInjection0.6 mg/1mLSubcutaneousRECORDATI RARE DISEASES, INC.2012-12-14Not applicableUS flag
SigniforInjection, solution0.6 mgSubcutaneousNovartis Europharm Limited2012-04-24Not applicableEU flag
SigniforInjection, powder, for suspension20 mgIntramuscularNovartis Europharm Limited2012-04-24Not applicableEU flag
SigniforInjection, solution0.9 mgSubcutaneousNovartis Europharm Limited2012-04-24Not applicableEU flag
SigniforInjection, solution0.6 mgSubcutaneousNovartis Europharm Limited2012-04-24Not applicableEU flag
SigniforSolution0.3 mgSubcutaneousNovartis2013-11-26Not applicableCanada flag
SigniforInjection, solution0.3 mgSubcutaneousNovartis Europharm Limited2012-04-24Not applicableEU flag
SigniforInjection, powder, for suspension40 mgIntramuscularNovartis Europharm Limited2012-04-24Not applicableEU flag
Additional Data Available
  • Application Number
    Application Number
    Available for Purchase

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code
    Available for Purchase

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories

ATC Codes
H01CB05 — Pasireotide
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as oligopeptides. These are organic compounds containing a sequence of between three and ten alpha-amino acids joined by peptide bonds.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Oligopeptides
Alternative Parents
Cyclic peptides / Macrolactams / 3-alkylindoles / Alpha amino acids and derivatives / Phenol ethers / Phenoxy compounds / Alkyl aryl ethers / Substituted pyrroles / Pyrrolidines / Heteroaromatic compounds
show 11 more
Substituents
3-alkylindole / Alkyl aryl ether / Alpha-amino acid or derivatives / Alpha-oligopeptide / Amine / Amino acid or derivatives / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Carbamic acid ester
show 28 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
homodetic cyclic peptide, peptide hormone (CHEBI:72312)

Chemical Identifiers

UNII
98H1T17066
CAS number
396091-73-9
InChI Key
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[[email protected]@H]1NC(=O)[[email protected]@H](CC2=CNC3=C2C=CC=C3)NC(=O)[[email protected]@H](NC(=O)[[email protected]@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

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]
KEGG Drug
D10147
PubChem Compound
9941444
PubChem Substance
175427082
ChemSpider
8117062
RxNav
1364105
ChEBI
72312
ChEMBL
CHEMBL3349607
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Pasireotide
AHFS Codes
  • 68:29.04 — Somatostatin Agonists
FDA label
Download (567 KB)
MSDS
Download (567 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingPreventionNeoplasms, Pancreatic / Pancreatic Fistula1
4Active Not RecruitingTreatmentAcromegaly / Cushing's Disease / Dumping Syndrome / Ectopic ACTH Secreting (EAS) Tumors / Melanoma Negative for bRAF / Melanoma Negative for nRAS / Neuroendocrine Tumors / Pituitary Neoplasms / Prostate Cancer1
4CompletedSupportive CareAcromegaly / Cushing's Disease1
4CompletedTreatmentBMI >30 kg/m2 / General Surgery / Hypoglycemia1
4CompletedTreatmentCushing's Disease1
4Unknown StatusTreatmentAcromegaly1
4Unknown StatusTreatmentReactive Hypoglycemia1
4WithdrawnTreatmentGastro-enteropancreatic Neuroendocrine Tumor1
3CompletedTreatmentAcromegaly3
3CompletedTreatmentCushing's Disease3

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
InjectionSubcutaneous0.3 mg/1mL
InjectionSubcutaneous0.6 mg/1mL
InjectionSubcutaneous0.9 mg/1mL
Injection, powder, for suspensionIntramuscular10 MG
Injection, powder, for suspensionIntramuscular20 mg
Injection, powder, for suspensionIntramuscular30 MG
Injection, powder, for suspensionIntramuscular40 mg
Injection, powder, for suspensionIntramuscular60 mg
Injection, solutionCutaneous; Parenteral0.3 MG
Injection, solutionCutaneous; Parenteral0.6 MG
Injection, solutionCutaneous; Parenteral0.9 MG
Injection, solutionSubcutaneous0.3 mg
Injection, solutionSubcutaneous0.6 mg
Injection, solutionSubcutaneous0.9 mg
Injection, solutionSubcutaneous300 mcg/1mL
Injection, solutionSubcutaneous600 mcg/1mL
Injection, solutionSubcutaneous900 mcg/1mL
SolutionSubcutaneous0.3 mg
SolutionSubcutaneous0.6 mg
SolutionSubcutaneous0.9 mg
InjectionSubcutaneous0.375 mg/ml
SolutionOral0.3 mg/1ml
SolutionOral0.6 mg/1ml
SolutionOral0.9 mg/1ml
Injection, powder, for suspension, extended release; kitIntramuscular10 mg
Injection, powder, for suspension, extended release; kitIntramuscular20 mg
Injection, powder, for suspension, extended release; kitIntramuscular30 mg
Injection, powder, for suspension, extended release; kitIntramuscular40 mg
Injection, powder, for suspension, extended release; kitIntramuscular60 mg
KitIntramuscular5 mg/1mL
Powder, for solutionOral20 mg
Powder, for solutionOral40 mg
Powder, for solutionOral60 mg
Injection, powder, for suspensionIntramuscular27.42 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US6225284No2001-05-012016-06-28US flag
US7473761No2009-01-062025-07-29US flag
US8299209No2012-10-302025-12-27US flag
US8822637No2014-09-022023-08-06US flag
US7759308No2010-07-202026-10-25US flag
US9351923No2016-05-312028-05-23US flag
Additional Data Available
  • Filed On
    Filed On
    Available for Purchase

    The date on which a patent was filed with the relevant government.

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Properties

State
Solid
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 FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Kind
Protein
Organism
Humans
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 stim...
Gene Name
SSTR1
Uniprot ID
P30872
Uniprot Name
Somatostatin receptor type 1
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
Humans
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 ...
Gene Name
SSTR2
Uniprot ID
P30874
Uniprot Name
Somatostatin receptor type 2
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
Humans
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
Uniprot Name
Somatostatin receptor type 3
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
Humans
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 act...
Gene Name
SSTR5
Uniprot ID
P35346
Uniprot Name
Somatostatin receptor type 5
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]

Enzymes

Kind
Protein
Organism
Humans
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

Drug created on March 19, 2008 10:46 / Updated on November 30, 2020 13:38

Pbdb medl 1