Pasireotide
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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.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Management of Acromegaly •••••••••••• ••••••••• Management of Cushing's disease •••••••••••• ••••• ••••••••• ••••••• •• ••• •• •••••• •• ••• ••• •••• •••••••• ••••••••• Management of Cushing's disease •••••••••••• ••••••••• ••••••• •• ••• •• •••••• •• ••• ••• •••• •••••••• ••••••••• - Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- 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.
Target Actions Organism ASomatostatin receptor type 3 inhibitorHumans ASomatostatin receptor type 1 inhibitorHumans ASomatostatin receptor type 2 inhibitorHumans ASomatostatin receptor type 5 inhibitorHumans - 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
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- 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
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbemaciclib The metabolism of Abemaciclib can be decreased when combined with Pasireotide. Acalabrutinib The metabolism of Acalabrutinib can be decreased when combined with Pasireotide. Acarbose The therapeutic efficacy of Acarbose can be decreased when used in combination with Pasireotide. Acebutolol Acebutolol may increase the bradycardic activities of Pasireotide. Acenocoumarol The serum concentration of Acenocoumarol can be increased when it is combined with Pasireotide. - Food Interactions
- No interactions found.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Product Ingredients
Ingredient UNII CAS InChI Key Pasireotide acetate 662X0VFR9L 396091-76-2 WFKFNBBHVLMWQH-QKXVGOHISA-N Pasireotide diaspartate I4P76SY3N4 820232-50-6 NEEFMPSSNFRRNC-HQUONIRXSA-N Pasireotide pamoate 04F55A7UZ3 396091-79-5 HSXBEUMRBMAVDP-QKXVGOHISA-N - International/Other Brands
- Signifor / Signifor LAR
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Signifor Injection, powder, for suspension 60 mg Intramuscular Recordati Rare Diseases 2016-09-20 Not applicable EU Signifor Injection, solution 0.3 mg Subcutaneous Recordati Rare Diseases 2016-09-20 Not applicable EU Signifor Injection, powder, for suspension 40 mg Intramuscular Recordati Rare Diseases 2016-09-20 Not applicable EU Signifor Solution 0.6 mg / mL Subcutaneous Recordati Rare Diseases 2013-11-26 Not applicable Canada Signifor Injection, solution 0.9 mg Subcutaneous Recordati Rare Diseases 2016-09-20 Not applicable EU
Categories
- ATC Codes
- H01CB05 — Pasireotide
- Drug Categories
- Amino Acids, Peptides, and Proteins
- Bradycardia-Causing Agents
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (weak)
- Cytochrome P-450 Enzyme Inhibitors
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Hyperglycemia-Associated Agents
- Hypoglycemia-Associated Agents
- Hypothalamic Hormones
- Nerve Tissue Proteins
- Neuropeptides
- Pancreatic Hormones
- Peptide Hormones
- Peptides
- Pituitary and Hypothalamic Hormones and Analogues
- Pituitary Hormone Release Inhibiting Hormones
- Potential QTc-Prolonging Agents
- Proteins
- QTc Prolonging Agents
- Somatostatin Agonists
- Somatostatin and Analogues
- Somatostatin Receptor Agonists
- Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins
- 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
- 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]
- External Links
- KEGG Drug
- D10147
- PubChem Compound
- 9941444
- PubChem Substance
- 175427082
- ChemSpider
- 8117062
- BindingDB
- 50474236
- 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
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Approved for Marketing Not Available Acromegaly 1 somestatus stop reason just information to hide Not Available Completed Not Available Surgical Complications 1 somestatus stop reason just information to hide Not Available No Longer Available Not Available Congenital Hyperinsulinism (CHI) 1 somestatus stop reason just information to hide 4 Active Not Recruiting Prevention Pancreatic Fistula / Pancreatic Neoplasms 1 somestatus stop reason just information to hide 4 Completed Supportive Care Acromegaly / Cushing's Disease 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection Subcutaneous 0.3 mg/1mL Injection Subcutaneous 0.6 mg/1mL Injection Subcutaneous 0.9 mg/1mL Injection, powder, for suspension Intramuscular 10 mg Injection, powder, for suspension Intramuscular 30 mg Injection, powder, for suspension Intramuscular; Parenteral 10 MG Injection, powder, for suspension Intramuscular; Parenteral 20 MG Injection, powder, for suspension Intramuscular; Parenteral 30 MG Injection, powder, for suspension Intramuscular; Parenteral 40 MG Injection, powder, for suspension Intramuscular; Parenteral 60 MG Solution Subcutaneous 0.3 mg / mL Solution Subcutaneous 0.6 mg / mL Solution Subcutaneous 0.9 mg / mL Solution 0.3 mg/1ml Solution 0.6 mg/1ml Solution 0.9 mg/1ml Injection Subcutaneous Injection, solution Subcutaneous 0.3 mg/1ml Injection Subcutaneous 0.375 mg/ml Solution Oral 0.3 mg/1ml Injection, solution Subcutaneous 0.6 mg/1ml Solution Oral 0.6 mg/1ml Injection, solution Subcutaneous 0.9 mg/1ml Solution Oral 0.9 mg/1ml Injection, powder, for suspension, extended release; kit Intramuscular 10 mg Injection, powder, for suspension, extended release; kit Intramuscular 20 mg Injection, powder, for suspension, extended release; kit Intramuscular 30 mg Injection, powder, for suspension, extended release; kit Intramuscular 40 mg Injection, powder, for suspension, extended release; kit Intramuscular 60 mg Injection, powder, for suspension; kit Intramuscular 10 mg/1mL Injection, powder, for suspension; kit Intramuscular 15 mg/1mL Injection, powder, for suspension; kit Intramuscular 20 mg/1mL Injection, powder, for suspension; kit Intramuscular 30 mg/1mL Injection, powder, for suspension; kit Intramuscular 5 mg/1mL Kit Intramuscular 5 mg/1mL Injection, powder, for suspension 10 mg/1vial Injection, powder, for suspension 20 mg/1vial Injection, powder, for suspension 30 mg/1vial Injection, powder, for suspension 40 mg/1vial Powder, for solution Oral 20 mg Powder, for solution Oral 40 mg Powder, for solution Oral 60 mg Injection, powder, for suspension Intramuscular 20 mg Injection, powder, for suspension Intramuscular 40 mg Injection, powder, for suspension Intramuscular 60 mg Injection, powder, for suspension 60 mg/1vial Injection, solution Subcutaneous 0.3 mg Injection, solution Subcutaneous 0.6 mg Injection, solution Subcutaneous 0.9 mg Solution Subcutaneous 0.3 mg Solution Subcutaneous 0.6 mg Solution Subcutaneous 0.9 mg Injection, powder, for suspension Intramuscular 27.42 mg - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US6225284 No 2001-05-01 2016-06-28 US US7473761 No 2009-01-06 2025-07-29 US US8299209 No 2012-10-30 2025-12-27 US US8822637 No 2014-09-02 2023-08-06 US US7759308 No 2010-07-20 2026-10-25 US US9351923 No 2016-05-31 2028-05-23 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source water solubility Soluble in water. From The Merck Index. - Predicted Properties
Property Value Source Water Solubility 0.00203 mg/mL ALOGPS logP 3.03 ALOGPS logP 2.67 Chemaxon logS -5.7 ALOGPS pKa (Strongest Acidic) 9.08 Chemaxon pKa (Strongest Basic) 10.41 Chemaxon Physiological Charge 2 Chemaxon Hydrogen Acceptor Count 10 Chemaxon Hydrogen Donor Count 9 Chemaxon Polar Surface Area 281.2 Å2 Chemaxon Rotatable Bond Count 18 Chemaxon Refractivity 286.66 m3·mol-1 Chemaxon Polarizability 111.08 Å3 Chemaxon Number of Rings 8 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9926 Blood Brain Barrier - 0.5389 Caco-2 permeable - 0.8325 P-glycoprotein substrate Substrate 0.656 P-glycoprotein inhibitor I Non-inhibitor 0.6717 P-glycoprotein inhibitor II Non-inhibitor 0.6843 Renal organic cation transporter Non-inhibitor 0.777 CYP450 2C9 substrate Non-substrate 0.8878 CYP450 2D6 substrate Non-substrate 0.758 CYP450 3A4 substrate Substrate 0.521 CYP450 1A2 substrate Non-inhibitor 0.7641 CYP450 2C9 inhibitor Non-inhibitor 0.7676 CYP450 2D6 inhibitor Non-inhibitor 0.8704 CYP450 2C19 inhibitor Inhibitor 0.5307 CYP450 3A4 inhibitor Inhibitor 0.575 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.6561 Ames test Non AMES toxic 0.7722 Carcinogenicity Non-carcinogens 0.8568 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 2.4609 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.8711 hERG inhibition (predictor II) Inhibitor 0.7476
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 306.73254 predictedDeepCCS 1.0 (2019) [M+H]+ 308.3857 predictedDeepCCS 1.0 (2019) [M+Na]+ 314.54257 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Receptor for somatostatin-14 and -28. This receptor is coupled via pertussis toxin sensitive G proteins to inhibition of adenylyl cyclase
- Specific Function
- G protein-coupled receptor activity
- Gene Name
- SSTR3
- Uniprot ID
- P32745
- Uniprot Name
- Somatostatin receptor type 3
- Molecular Weight
- 45846.995 Da
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. [Article]
- 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]
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General 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
- Specific Function
- neuropeptide binding
- Gene Name
- SSTR1
- Uniprot ID
- P30872
- Uniprot Name
- Somatostatin receptor type 1
- Molecular Weight
- 42685.77 Da
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. [Article]
- 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]
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General 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 in pancreatic alpha- and beta-cells where it mediates the inhibitory effect of somatostatin-14 on hormone secretion. Inhibits cell growth through enhancement of MAPK1 and MAPK2 phosphorylation and subsequent up-regulation of CDKN1B. Stimulates neuronal migration and axon outgrowth and may participate in neuron development and maturation during brain development. Mediates negative regulation of insulin receptor signaling through PTPN6. Inactivates SSTR3 receptor function following heterodimerization
- Specific Function
- neuropeptide binding
- Gene Name
- SSTR2
- Uniprot ID
- P30874
- Uniprot Name
- Somatostatin receptor type 2
- Molecular Weight
- 41332.37 Da
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. [Article]
- 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]
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General 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
- Specific Function
- neuropeptide binding
- Gene Name
- SSTR5
- Uniprot ID
- P35346
- Uniprot Name
- Somatostatin receptor type 5
- Molecular Weight
- 39201.925 Da
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. [Article]
- 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]
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
- Specific Function
- 1,8-cineole 2-exo-monooxygenase activity
- 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 August 26, 2024 19:24