ensifentrine   Click here for help

GtoPdb Ligand ID: 11865

Synonyms: Ohtuvayre® | RPL554 | VMX 554 | VMX-554 | VMX554
Approved drug Immunopharmacology Ligand
ensifentrine is an approved drug (FDA (2024))
Compound class: Synthetic organic
Comment: Ensifentrine (RPL-554) is an inhibitor of phosphodiesterases 3 and 4 (PDE3 and PDE4) [3]. It has bronchodilatory action that is mediated by inhibition of PDE3 in airway smooth muscle [9,11] that is associated with short-term improvement in lung function [5]. Ensifentrine was developed for therapeutic potential in asthma and chronic obstructive pulmonary disease (COPD) [6-7]. It also also has anti-inflammatory effects in vitro (e.g. reducing TNFα release from human monocytes) and in vivo, likely through inhibtion of PDE4 expressed by inflammatory cells in the lungs [10]. Ensifentrine is active when delivered orally or by inhalation (nebulised) [2].

COVID-19: A pilot study of ensifentrine in hospitalised COVID-19 patients was initiated in mid-late 2020, but by 2024 no results had been published.

FDA approval of ensifentrine in 2024 made this the first COPD inhalation drug with a new mechanism of action to reach the clinic in more than 20 years.
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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
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 4
Hydrogen bond donors 2
Rotatable bonds 7
Topological polar surface area 112.87
Molecular weight 477.24
XLogP 3.7
No. Lipinski's rules broken 0

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 COc1cc2c(cc1OC)CCn1c2cc(=Nc2c(C)cc(cc2C)C)n(c1=O)CCNC(=O)N
Isomeric SMILES Cc1cc(c(c(c1)C)N=c1cc2c3cc(c(cc3CCn2c(=O)n1CCNC(=O)N)OC)OC)C
InChI InChI=1S/C26H31N5O4/c1-15-10-16(2)24(17(3)11-15)29-23-14-20-19-13-22(35-5)21(34-4)12-18(19)6-8-30(20)26(33)31(23)9-7-28-25(27)32/h10-14H,6-9H2,1-5H3,(H3,27,28,32)
InChI Key CSOBIBXVIYAXFM-UHFFFAOYSA-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/)
Classification Click here for help
Compound class Synthetic organic
Approved drug? Yes (FDA (2024))
IUPAC Name Click here for help
2-[9,10-dimethoxy-4-oxo-2-(2,4,6-trimethylphenyl)imino-6,7-dihydropyrimido[6,1-a]isoquinolin-3-yl]ethylurea
International Nonproprietary Names Click here for help
INN number INN
10726 ensifentrine
Synonyms Click here for help
Ohtuvayre® | RPL554 | VMX 554 | VMX-554 | VMX554
Database Links Click here for help
ChEMBL Ligand CHEMBL4594287
GtoPdb PubChem SID 461663421
PubChem CID 9934746
Search Google for chemical match using the InChIKey CSOBIBXVIYAXFM-UHFFFAOYSA-N
Search Google for chemicals with the same backbone CSOBIBXVIYAXFM
Search PubMed clinical trials ensifentrine
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Search PubMed titles/abstracts ensifentrine
UniChem Compound Search for chemical match using the InChIKey CSOBIBXVIYAXFM-UHFFFAOYSA-N
UniChem Connectivity Search for chemical match using the InChIKey CSOBIBXVIYAXFM-UHFFFAOYSA-N