◎ Sugi Atlas

Atlas / Drug / Ensifentrine

Ensifentrine

drug
On this page

Also known as EnsifentrinaLs-193,855Ls-193855OhtuvayreRPL-554RPL554

Summary

Ensifentrine (CHEMBL4594287) is an approved small molecule targeting PDE3A and PDE4A; indicated across 5 conditions including chronic obstructive pulmonary disease and severe acute respiratory syndrome.

At a glance

  • Status: Approved (max clinical phase 4)
  • Modality: Small molecule
  • Targets: 2 (PDE3A, PDE4A)
  • Indications: 5 conditions
  • Clinical trials: 13
  • Chemistry: 477.6 Da · C26H31N5O4

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL4594287
NameEnsifentrine
TypeSmall molecule
Max phase4
FDA approvedno
PubChem CID9934746
Molecular formulaC26H31N5O4
Molecular weight477.6
InChIKeyCSOBIBXVIYAXFM-UHFFFAOYSA-N

SMILES: CC1=CC(=C(C(=C1)C)N=C2C=C3C4=CC(=C(C=C4CCN3C(=O)N2CCNC(=O)N)OC)OC)C

IUPAC name: 2-[9,10-dimethoxy-4-oxo-2-(2,4,6-trimethylphenyl)imino-6,7-dihydropyrimido[6,1-a]isoquinolin-3-yl]ethylurea

Also known as: Ensifentrina, Ensifentrine, Ls-193,855, Ls-193855, Ohtuvayre, RPL-554, RPL554, ENSIFENTRINE

Patent coverage: 153 distinct patent families (499 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 495 (99%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

GeneTargetActionpAffinityCancer dependencyUniProt
PDE3Aphosphodiesterase 3AInhibition9.40.1%Q14432
PDE4Aphosphodiesterase 4AInhibition5.830.4%P27815

Broader ChEMBL bioactivity targets: 1 (assay-derived). Sample: Phosphodiesterase 4.

Bioactivity

ChEMBL activities: 1 potent at pChembl ≥ 5 of 1 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

TargetpChemblTypeValueUnitActivity ID
PDE4A5.83IC501479nMCHEMBL_ACT_29223629

Target pathways

Aggregated over 2 target gene(s): PDE3A, PDE4A.

Top Reactome pathways

2 total, by targets touching each:

PathwayTargetsGenes
G alpha (s) signalling events2PDE3A, PDE4A
DARPP-32 events1PDE4A

Dominant GO biological processes

GO termTargets
G protein-coupled receptor signaling pathway2
negative regulation of cAMP/PKA signal transduction2
signal transduction2
oocyte maturation1
lipid metabolic process1
response to xenobiotic stimulus1
regulation of meiotic nuclear division1
negative regulation of apoptotic process1
negative regulation of vascular permeability1
positive regulation of vascular permeability1
positive regulation of oocyte development1
regulation of ribonuclease activity1
cellular response to cGMP1
cellular response to transforming growth factor beta stimulus1
apoptotic signaling pathway1

Indications & clinical

Indications

5 indications (2 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

IndicationTrial phaseMONDOEFO
chronic obstructive pulmonary disease4MONDO:0005002EFO:0000341
severe acute respiratory syndrome2MONDO:0005091MONDO:0100096
asthma2MONDO:0004979MONDO:0004979
cystic fibrosis2MONDO:0009061MONDO:0009061

1 further indication record had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 13.

Phase distribution

PhaseTrials
PHASE28
PHASE33
PHASE12

Top trials by phase / activity

NCTPhaseStatusTitle
NCT04535986PHASE3COMPLETEDA Phase 3 Clinical Trial to Evaluate the Safety and Efficacy of Ensifentrine in Patients With COPD
NCT04542057PHASE3COMPLETEDA Phase 3 Trial to Evaluate the Safety and Efficacy of Ensifentrine in Patients With COPD
NCT05743075PHASE3COMPLETEDA Study to Evaluate the Efficacy and Safety of Ensifentrine for 24 Weeks in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease
NCT05270525PHASE2RECRUITINGEffect of Ensifentrine on Sputum Markers of Inflammation in COPD
NCT07016412PHASE2RECRUITINGA Phase IIb Ensifentrine-glycopyrrolate Fixed-dose Combination Dose Ranging Study in Subjects With COPD
NCT02427165PHASE2COMPLETEDComparison of RPL554 With Placebo and Salbutamol in Asthmatic Patients
NCT02542254PHASE2COMPLETEDThe Effects of RPL554 on Top of Standard COPD Reliever Medications
NCT02919995PHASE2COMPLETEDA Study of RPL554 in Patients With Cystic Fibrosis
NCT03443414PHASE2COMPLETEDDose Ranging Study of RPL554 in Chronic Obstructive Pulmonary Disease (COPD) Patients
NCT03673670PHASE2COMPLETEDBronchodilator Effect of RPL554 Administered in Addition to Tiotropium/Olodaterol in Patients With COPD
NCT07132983PHASE2COMPLETEDA Phase II Study to Assess the Pharmacokinetics, Pharmacodynamics, and Safety of Single Inhaled Doses of Ensifentrine-glycopyrrolate Fixed Dose Combination, Ensifentrine, and Glycopyrrolate in Subjects With Chronic Obstructive Pulmonary Disease
NCT02307162PHASE1COMPLETEDSAD/MAD Study of a New Formulation of Nebulised RPL554 in Healthy Subjects and COPD Subjects
NCT05758428PHASE1COMPLETEDA Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Nebulized Ensifentrine in Healthy Chinese Subjects

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

300 molecules share ≥1 primary target. Top 60 by shared-target count:

MoleculeSourceStatusShared targets
ApremilastChEMBL + PubChemPhase 4 (approved)PDE3A, PDE4A
gentian violetChEMBL + PubChemPhase 4 (approved)PDE3A, PDE4A
LOSARTANChEMBL + PubChemPhase 4 (approved)PDE3A, PDE4A
TadalafilChEMBL + PubChemPhase 4 (approved)PDE3A, PDE4A
UmeclidiniumChEMBL + PubChemPhase 4 (approved)PDE3A, PDE4A
ACARBOSEChEMBLPhase 4 (approved)PDE3A, PDE4A
ALECTINIBChEMBLPhase 4 (approved)PDE3A, PDE4A
CRISABOROLEChEMBLPhase 4 (approved)PDE3A, PDE4A
DEQUALINIUMChEMBLPhase 4 (approved)PDE3A, PDE4A
DIPYRIDAMOLEChEMBLPhase 4 (approved)PDE3A, PDE4A
ENOXIMONEChEMBLPhase 4 (approved)PDE3A, PDE4A
ESTRADIOL CYPIONATEChEMBLPhase 4 (approved)PDE3A, PDE4A
ETHINYL ESTRADIOLChEMBLPhase 4 (approved)PDE3A, PDE4A
FEXOFENADINEChEMBLPhase 4 (approved)PDE3A, PDE4A
HEXACHLOROPHENEChEMBLPhase 4 (approved)PDE3A, PDE4A
IBUDILASTChEMBLPhase 4 (approved)PDE3A, PDE4A
INAMRINONEChEMBLPhase 4 (approved)PDE3A, PDE4A
MILRINONEChEMBLPhase 4 (approved)PDE3A, PDE4A
PHENAZOPYRIDINEChEMBLPhase 4 (approved)PDE3A, PDE4A
PHYTONADIONEChEMBLPhase 4 (approved)PDE3A, PDE4A
PRIMAQUINEChEMBLPhase 4 (approved)PDE3A, PDE4A
SILDENAFILChEMBLPhase 4 (approved)PDE3A, PDE4A
TELMISARTANChEMBLPhase 4 (approved)PDE3A, PDE4A
TICAGRELORChEMBLPhase 4 (approved)PDE3A, PDE4A
TRIMETREXATEChEMBLPhase 4 (approved)PDE3A, PDE4A
TROGLITAZONEChEMBLPhase 4 (approved)PDE3A, PDE4A
VARDENAFILChEMBLPhase 4 (approved)PDE3A, PDE4A
MENATETRENONEChEMBLPhase 3PDE3A, PDE4A
PAPAVERINEChEMBLPhase 3PDE3A, PDE4A
ADIBENDANChEMBLPhase 2PDE3A, PDE4A
BUCLADESINEChEMBLPhase 2PDE3A, PDE4A
CLOFOCTOLChEMBLPhase 2PDE3A, PDE4A
ENPROFYLLINEChEMBLPhase 2PDE3A, PDE4A
ETHAVERINEChEMBLPhase 2PDE3A, PDE4A
IMAZODANChEMBLPhase 2PDE3A, PDE4A
INDOLIDANChEMBLPhase 2PDE3A, PDE4A
LIXAZINONEChEMBLPhase 2PDE3A, PDE4A
OLPRINONEChEMBLPhase 2PDE3A, PDE4A
ORISMILASTChEMBLPhase 2PDE3A, PDE4A
TOFISOPAMChEMBLPhase 2PDE3A, PDE4A
TRICLOCARBANChEMBLPhase 2PDE3A, PDE4A
ZARDAVERINEChEMBLPhase 2PDE3A, PDE4A
EchothiophatePubChemApprovedPDE3A, PDE4A
levocarnitinePubChemApprovedPDE3A, PDE4A
PerindoprilPubChemApprovedPDE3A, PDE4A
PimavanserinPubChemApprovedPDE3A, PDE4A
podofiloxPubChemApprovedPDE3A, PDE4A
Propylene GlycolPubChemApprovedPDE3A, PDE4A
PyrazinamidePubChemApprovedPDE3A, PDE4A
PyridoxinePubChemApprovedPDE3A, PDE4A
QuinaprilatPubChemApprovedPDE3A, PDE4A
VorapaxarPubChemApprovedPDE3A, PDE4A
CLOFARABINEChEMBL + PubChemPhase 4 (approved)PDE3A
IDELALISIBChEMBL + PubChemPhase 4 (approved)PDE3A
TAFAMIDISChEMBL + PubChemPhase 4 (approved)PDE3A
TAVABOROLEChEMBL + PubChemPhase 4 (approved)PDE3A
2-MERCAPTOETHANESULFONIC ACIDChEMBLPhase 4 (approved)PDE4A
ADENOSINEChEMBLPhase 4 (approved)PDE3A
ALENDRONIC ACIDChEMBLPhase 4 (approved)PDE3A
AMINOGLUTETHIMIDEChEMBLPhase 4 (approved)PDE3A

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 30

This page pulls from 30 datasets indexed by BioBTree:

chebichembl_activitychembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsdepmapefoensemblentrezgogoparentgtopdbgtopdb_interactiongtopdb_ligandhgncmeshmondomsigdbpatent_compoundpharmgkbpharmgkb_guidelinepubchempubchem_activityreactomereactomeparentrefseqtranscriptuniprot