latanoprostene bunod   Click here for help

GtoPdb Ligand ID: 9635

Synonyms: BOL-303259-X | NCX-116 | PF-3187207 | Vyzulta®
Approved drug
latanoprostene bunod is an approved drug (FDA (2017))
Compound class: Synthetic organic
Comment: Latanoprostene bunod is a NO-donating analogue of the prostaglandin F2α agonist latanoprost (isopropyl ester) [3]. This compound benefits from the additive hypotensive actions of both the prostaglandin agonist and NO. Latanoprostene bunod is the first NO-donating prostaglandin analogue to be granted FDA marketing approval [2,4].
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species

latanoprostene bunod is commercially available from our sponsors

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 3
Rotatable bonds 19
Topological polar surface area 139.36
Molecular weight 507.28
XLogP 4.47
No. Lipinski's rules broken 1

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 OC(CCc1ccccc1)CCC1C(O)CC(C1CC=CCCCC(=O)OCCCCO[N+](=O)[O-])O
Isomeric SMILES O[C@@H](CCc1ccccc1)CC[C@H]1[C@H](O)C[C@@H]([C@@H]1C/C=C\CCCC(=O)OCCCCO[N+](=O)[O-])O
InChI InChI=1S/C27H41NO8/c29-22(15-14-21-10-4-3-5-11-21)16-17-24-23(25(30)20-26(24)31)12-6-1-2-7-13-27(32)35-18-8-9-19-36-28(33)34/h1,3-6,10-11,22-26,29-31H,2,7-9,12-20H2/b6-1-/t22-,23+,24+,25-,26+/m0/s1
InChI Key LOVMMUBRQUFEAH-UIEAZXIASA-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/)
Bioactivity Comments
In vitro, BOL-303259-X increases guanylyl cyclase activity (NO-mediated cGMP formation) in PC12 (rat) and HEK293 (human) cells [3]. It is active in a variety of preclinical animal models [3]. Bioactivity vs. soluble guanylyl cyclase has been mapped to guanylyl cyclase α1β1 (GC-1), but as enzyme isoform is not specified, activation of the GC-2 isoform cannot be discounted. The value ascribed for agonist activity at the prostanoid FP receptor is derived from the published affinity of the parent compound active metabolite, latanoprost (free acid form).
Selectivity at GPCRs
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
FP receptor Hs Agonist Agonist ~8.6 pKi - 1,3
⤷ pKi ~8.6 (Ki ~2.51x10-9 M) [1,3]
Description: Value based on agonist activity of latanoprost.