Pasireotide

Identification

Summary

Pasireotide is a somatostatin analog used in the treatment of Cushing’s disease, specifically for those patients whom pituitary surgery is not appropriate.

Brand Names
Signifor
Generic Name
Pasireotide
DrugBank Accession Number
DB06663
Background

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
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.

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Management ofAcromegaly•••••••••••••••••••••
Management ofCushing's disease•••••••••••••••••••••••••• ••••••• •• ••• •• •••••• •• ••• ••• •••• •••••••••••••••••
Management ofCushing's disease••••••••••••••••••••• ••••••• •• ••• •• •••••• •• ••• ••• •••• •••••••••••••••••
Contraindications & Blackbox Warnings
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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
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Toxicity

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

Pathways
Not Available
Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Not Available

Interactions

Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
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.
AcebutololAcebutolol may increase the bradycardic activities of Pasireotide.
AcenocoumarolThe serum concentration of Acenocoumarol can be increased when it is combined with Pasireotide.
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
SigniforInjection0.9 mg/1mLSubcutaneousRECORDATI RARE DISEASES, INC.2012-12-14Not applicableUS flag
SigniforSolution0.3 mg / mLSubcutaneousRecordati Rare Diseases Canada Inc2013-11-26Not applicableCanada flag
SigniforInjection, solution0.9 mgSubcutaneousRecordati Rare Diseases2016-09-20Not applicableEU flag
SigniforInjection0.6 mg/1mLSubcutaneousNovartis Pharmaceuticals Corporation2012-12-142022-09-30US flag
SigniforInjection, solution0.6 mgSubcutaneousRecordati Rare Diseases2016-09-20Not applicableEU flag

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)
Affected organisms
  • Humans and other mammals

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-yl)methyl]-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[C@H](CN2C(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](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. [Article]
KEGG Drug
D10147
PubChem Compound
9941444
PubChem Substance
175427082
ChemSpider
8117062
BindingDB
50474236
RxNav
1364105
ChEBI
72312
ChEMBL
CHEMBL3349607
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Pasireotide
FDA label
Download (567 KB)
MSDS
Download (567 KB)

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">

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 suspensionIntramuscular30 mg
Injection, powder, for suspensionIntramuscular; Parenteral10 MG
Injection, powder, for suspensionIntramuscular; Parenteral20 MG
Injection, powder, for suspensionIntramuscular; Parenteral30 MG
Injection, powder, for suspensionIntramuscular; Parenteral40 MG
Injection, powder, for suspensionIntramuscular; Parenteral60 MG
SolutionSubcutaneous0.3 mg / mL
SolutionSubcutaneous0.6 mg / mL
SolutionSubcutaneous0.9 mg / mL
Solution0.3 mg/1ml
Solution0.6 mg/1ml
Solution0.9 mg/1ml
InjectionSubcutaneous
Injection, solutionSubcutaneous0.3 mg/1ml
InjectionSubcutaneous0.375 mg/ml
SolutionOral0.3 mg/1ml
Injection, solutionSubcutaneous0.6 mg/1ml
SolutionOral0.6 mg/1ml
Injection, solutionSubcutaneous0.9 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
Injection, powder, for suspension; kitIntramuscular10 mg/1mL
Injection, powder, for suspension; kitIntramuscular15 mg/1mL
Injection, powder, for suspension; kitIntramuscular20 mg/1mL
Injection, powder, for suspension; kitIntramuscular30 mg/1mL
Injection, powder, for suspension; kitIntramuscular5 mg/1mL
KitIntramuscular5 mg/1mL
Injection, powder, for suspension10 mg/1vial
Injection, powder, for suspension20 mg/1vial
Injection, powder, for suspension30 mg/1vial
Injection, powder, for suspension40 mg/1vial
Powder, for solutionOral20 mg
Powder, for solutionOral40 mg
Powder, for solutionOral60 mg
Injection, powder, for suspensionIntramuscular20 mg
Injection, powder, for suspensionIntramuscular40 mg
Injection, powder, for suspensionIntramuscular60 mg
Injection, powder, for suspension60 mg/1vial
Injection, solutionSubcutaneous0.3 mg
Injection, solutionSubcutaneous0.6 mg
Injection, solutionSubcutaneous0.9 mg
SolutionSubcutaneous0.3 mg
SolutionSubcutaneous0.6 mg
SolutionSubcutaneous0.9 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

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilitySoluble in water.From The Merck Index.
Predicted Properties
PropertyValueSource
Water Solubility0.00203 mg/mLALOGPS
logP3.03ALOGPS
logP2.67Chemaxon
logS-5.7ALOGPS
pKa (Strongest Acidic)9.08Chemaxon
pKa (Strongest Basic)10.41Chemaxon
Physiological Charge2Chemaxon
Hydrogen Acceptor Count10Chemaxon
Hydrogen Donor Count9Chemaxon
Polar Surface Area281.2 Å2Chemaxon
Rotatable Bond Count18Chemaxon
Refractivity286.66 m3·mol-1Chemaxon
Polarizability111.08 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/MSsplash10-0002-9000000000-2d2587a5c0b657999431
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-002g-7000000098-52563fb45096d2a54ae5
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-03dm-9000000007-c2eaf9d88c2003b7b4db
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-014i-2000000090-0e1b753c035bc6356f92
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-000y-9700000002-cf92039463fd5d115d0b
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-00ng-5400000092-0ecfeb30018c197ba456
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-306.73254
predicted
DeepCCS 1.0 (2019)
[M+H]+308.3857
predicted
DeepCCS 1.0 (2019)
[M+Na]+314.54257
predicted
DeepCCS 1.0 (2019)

Targets

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insights and accelerate drug research.
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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. [Article]
  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. [Article]
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. [Article]
  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. [Article]
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. [Article]
  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. [Article]
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. [Article]
  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. [Article]

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 at March 19, 2008 16:46 / Updated at February 02, 2024 22:53