Unoprostone

Identification

Name
Unoprostone
Accession Number
DB06826
Type
Small Molecule
Groups
Approved, Investigational
Description

Unoprostone isopropyl is a prostaglandin analogue. Ophthalmic Solution 0.15% is a synthetic docosanoid. Unoprostone isopropyl has the chemical name isopropyl (+)-(Z)-7-[(1R,2R,3R,5S)-3,5 dihydroxy-2-(3-oxodecyl)cyclopentyl]-5-heptenoate. The main indication of Unoprostane is treatment of glucoma.

Structure
Thumb
Synonyms
  • 13,14-dihydro-15-keto-20-ethyl PGF2α
External IDs
UF 021 / UF-021 / UF021
Product Ingredients
IngredientUNIICASInChI Key
Unoprostone isopropyl5M161S5O5P120373-24-2XXUPXHKCPIKWLR-JHUOEJJVSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ResculaSolution0.15 %OphthalmicNovartis Ophthalmics Novartis Pharmaceuticals (Canada) Inc2002-05-272006-01-18Canada
ResculaSolution / drops1.5 mg/1mLOphthalmicSucampo Pharma Americas, Llc2013-01-072014-12-31Us
Categories
UNII
6X4F561V3W
CAS number
120373-36-6
Weight
Average: 382.541
Monoisotopic: 382.271924324
Chemical Formula
C22H38O5
InChI Key
TVHAZVBUYQMHBC-SNHXEXRGSA-N
InChI
InChI=1S/C22H38O5/c1-2-3-4-5-8-11-17(23)14-15-19-18(20(24)16-21(19)25)12-9-6-7-10-13-22(26)27/h6,9,18-21,24-25H,2-5,7-8,10-16H2,1H3,(H,26,27)/b9-6-/t18-,19-,20+,21-/m1/s1
IUPAC Name
(5Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-(3-oxodecyl)cyclopentyl]hept-5-enoic acid
SMILES
CCCCCCCC(=O)CC[C@H]1[C@H](O)C[C@H](O)[C@@H]1C\C=C/CCCC(O)=O

Pharmacology

Indication

For the lowering of intraocular pressure in patients with open-angle glaucoma or ocular hypertension who are intolerant of other intraocular pressure lowering medications or insufficiently responsive (failed to achieve target IOP determined after multiple measurements over time) to another intraocular pressure lowering medication.

Associated Conditions
Pharmacodynamics

Unoprostone will begin to reduce IOP 30 minutes after ocular instillation.

Mechanism of action

Unoprostone is believed to reduce elevated intraocular pressure (IOP), by increasing the outflow of aqueous humor. The mechanism of action for the IOP-lowering effect of unoprostone is controversial. Early studies showed that unoprostone increases aqueous humor outflow through the uveoscleral pathway similar to the 20-carbon prostaglandin analogs, such as latanoprost.8 More recent evidence, however, shows that it may work, at least in part, through stimulation of Ca2+-activated BK and CIC-2 type channels, leading to increased trabecular meshwork outflow.

Absorption

After application to the eye, unoprostone isopropyl is absorbed through the cornea and conjunctival epithelium where it is hydrolyzed by esterases to unoprostone free acid. mean peak unoprostone free acid plasma concentration was <1.5 ng/mL and dro pped below the lower limit of quantitation (<0.250 ng/mL) 1 hour following instillation, indicating low systemic absorption and rapid plasma excretion.

Volume of distribution

Intended for local use only, very low systemic absorption.

Protein binding

Intended for local use only, very low systemic absorption.

Metabolism

After ocular application, unoprostone isopropyl is hydrolyzed by esterases in the cornea to its biological active metabolite, unoprostone free acid. Unoprostone free acid is then metabolized to several inactive metabolites with lower molecular weight and increased polarity via ε- or β-oxidation. No secondary conjugation is found and no significant effect on hepatic microsomal enzyme activity has been observed.

Route of elimination

Elimination of unoprostone free acid from human plasma is rapid. Plasma levels of unoprostone free acid dropped below the lower limit of quantitation ( < 0.25 ng/mL) 1 hour following ocular instillation. Urinary elimination is the predominant elimination route.

Half life

Half-life of Unoprostone is 14 minutes.

Clearance

Intended for local use only, very low systemic absorption.

Toxicity

LD50 in rats: 1g/Kg (subcutaneous), 93500 µg/Kg (IV).

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

Interactions

Drug Interactions
DrugInteraction
1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid may increase the hypotensive activities of Unoprostone.
AcebutololAcebutolol may increase the hypotensive activities of Unoprostone.
AceclofenacThe therapeutic efficacy of Unoprostone can be decreased when used in combination with Aceclofenac.
AcemetacinThe therapeutic efficacy of Unoprostone can be decreased when used in combination with Acemetacin.
Acetylsalicylic acidThe therapeutic efficacy of Unoprostone can be decreased when used in combination with Acetylsalicylic acid.
AlclofenacThe therapeutic efficacy of Unoprostone can be decreased when used in combination with Alclofenac.
AliskirenUnoprostone may increase the hypotensive activities of Aliskiren.
AlminoprofenThe therapeutic efficacy of Unoprostone can be decreased when used in combination with Alminoprofen.
AlprenololAlprenolol may increase the hypotensive activities of Unoprostone.
AmbrisentanAmbrisentan may increase the hypotensive activities of Unoprostone.
Food Interactions
Not Available

References

General References
  1. article [Link]
  2. Monogragh [Link]
External Links
PubChem Compound
5311236
PubChem Substance
347827802
ChemSpider
4470755
ChEBI
39455
ChEMBL
CHEMBL1201407
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Unoprostone
ATC Codes
S01EE02 — Unoprostone
FDA label
Download (36.9 KB)
MSDS
Download (32.4 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentDry Age-related Macular Degeneration1
3TerminatedTreatmentRetinitis Pigmentosa (RP)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
SolutionOphthalmic0.15 %
Solution / dropsOphthalmic1.5 mg/1mL
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6458836No2002-10-012021-07-09Us
US6770675No2004-08-032018-11-24Us

Properties

State
Liquid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0306 mg/mLALOGPS
logP3.99ALOGPS
logP3.91ChemAxon
logS-4.1ALOGPS
pKa (Strongest Acidic)4.31ChemAxon
pKa (Strongest Basic)-2.9ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area94.83 Å2ChemAxon
Rotatable Bond Count15ChemAxon
Refractivity107.68 m3·mol-1ChemAxon
Polarizability45.47 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

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

Taxonomy

Description
This compound belongs to the class of organic compounds known as prostaglandins and related compounds. These are unsaturated carboxylic acids consisting of a 20 carbon skeleton that also contains a five member ring, and are based upon the fatty acid arachidonic acid.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Fatty Acyls
Sub Class
Eicosanoids
Direct Parent
Prostaglandins and related compounds
Alternative Parents
Long-chain fatty acids / Hydroxy fatty acids / Unsaturated fatty acids / Cyclopentanols / Ketones / Cyclic alcohols and derivatives / Monocarboxylic acids and derivatives / Carboxylic acids / Organic oxides / Hydrocarbon derivatives
Substituents
Prostaglandin skeleton / Long-chain fatty acid / Hydroxy fatty acid / Cyclopentanol / Fatty acid / Unsaturated fatty acid / Cyclic alcohol / Ketone / Secondary alcohol / Carboxylic acid
Molecular Framework
Aliphatic homomonocyclic compounds
External Descriptors
oxo monocarboxylic acid, prostaglandins Falpha, ketone (CHEBI:39455) / Prostaglandins (LMFA03010204)

Drug created on September 14, 2010 10:21 / Updated on November 02, 2018 08:56