DT-Web

DB06663 - Pasireotide


Identification
Name Pasireotide
Accession Number DB06663
Type small molecule
Description Pasireotide is a synthetic long-acting cyclic hexapeptide with somatostatin-like activity. It is marketed as a diaspartate salt called Signifor(R), which is used in the treatment of Cushing's disease.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight Not Available
Groups approved
Monoisotopic Weight Not Available
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.
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.
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.
Protein binding Plasma protein binding is 88%.
Biotransformation 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%).
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
Interactions
Drug Interactions
Drug Mechanism of interaction
Mifepristone Avoid combination with mifepristone and other moderate to high risk QTc prolonging agents. The combinaton may enhance the QTc-prolonging effect of these drugs.
Food Interactions
  • Since Signifor(R) is administered subcutaneously, food has no effect.

Targets


Somatostatin receptor type 1
Name Somatostatin receptor type 1
Gene Name SSTR1
Pharmacological action unknown
Actions Not Available
References
  • 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
  • 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
DTHybrid score 1.3485
Somatostatin receptor type 2
Name Somatostatin receptor type 2
Gene Name SSTR2
Pharmacological action unknown
Actions Not Available
References
  • 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
  • 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
DTHybrid score 1.6541
Somatostatin receptor type 3
Name Somatostatin receptor type 3
Gene Name SSTR3
Pharmacological action unknown
Actions Not Available
References
  • 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
  • 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
DTHybrid score 1.0516
Somatostatin receptor type 5
Name Somatostatin receptor type 5
Gene Name SSTR5
Pharmacological action unknown
Actions Not Available
References
  • 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
  • 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
DTHybrid score 1.6533

Predictions


Id Partner name Gene Name Score
427 Substance-P receptor TACR1 0.277
1757 Myeloperoxidase MPO 0.2226
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