unoprostone isopropyl   Click here for help

GtoPdb Ligand ID: 8282

Synonyms: Rescula® (proposed trade name) | UF 021 | UF-021
Approved drug
unoprostone isopropyl is an approved drug (FDA (2000))
Compound class: Synthetic organic
Comment: Note that the INN for this compound is for the carboxylic acid, whereas the compound used clinically is the isopropyl ester.
Unoprostone was originally developed as an intraocular pressure-reducing agent for use in glaucoma, however use for this indication has been discontinued. The focus is now on unoprostone's ability to treat retinal disease [3,5].
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2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 5
Hydrogen bond donors 2
Rotatable bonds 17
Topological polar surface area 83.83
Molecular weight 424.32
XLogP 5.39
No. Lipinski's rules broken 2

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES CCCCCCCC(=O)CCC1C(O)CC(C1CC=CCCCC(=O)OC(C)C)O
Isomeric SMILES CCCCCCCC(=O)CC[C@H]1[C@H](O)C[C@@H]([C@@H]1C/C=C\CCCC(=O)OC(C)C)O
InChI InChI=1S/C25H44O5/c1-4-5-6-7-10-13-20(26)16-17-22-21(23(27)18-24(22)28)14-11-8-9-12-15-25(29)30-19(2)3/h8,11,19,21-24,27-28H,4-7,9-10,12-18H2,1-3H3/b11-8-/t21-,22-,23+,24-/m1/s1
InChI Key XXUPXHKCPIKWLR-JHUOEJJVSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
No information available.
Summary of Clinical Use Click here for help
Both the EMA and FDA have granted unoprostone isopropyl orphan drug status for the treatment of the rare condition retinitis pigmentosa (RP) [7]. A Phase 2I clinical trial assessing unoprostone isopropyl as a treatment for RP is ongoing. A Phase 2 study in patients with dry age-related macular degeneration has been completed.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Unoprostone isopropyl is a topically applied prostaglandin analogue, with a docosanoid-like structure. Docosanoids are signaling molecules with neuroprotective and anti-inflammatory actions [1]. The reported affinity of unoprostone for prostaglandin receptors is very low [4], suggesting an alternative mechanism of action. The beneficial effects of unoprostone in RP appear to be mediated by activation of Ca2+-activated K+ (BK) channels [6], with an EC50 for activation of BK channels by unoprostone of approximately 0.6 nM in human cortical cells [2].