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Sparsentan

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Also known as EsparsentanFilspariPS-433540PS433540RE-021

Summary

Sparsentan (CHEMBL539423) is an approved small-molecule angiotensin receptor antagonist (ATC C09XX01) targeting EDNRA and AGTR1; indicated across 3 conditions including iga glomerulonephritis and focal segmental glomerulosclerosis.

At a glance

  • Status: Approved (max clinical phase 4)
  • Modality: Small molecule
  • ATC class: C09XX01
  • Targets: 2 (EDNRA, AGTR1)
  • Indications: 3 conditions
  • Clinical trials: 13
  • Chemistry: 592.8 Da · C32H40N4O5S

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL539423
NameSparsentan
TypeSmall molecule
Max phase4
FDA approvedyes
PubChem CID10257882
ChEBICHEBI:229526
ATCC09XX01
Molecular formulaC32H40N4O5S
Molecular weight592.8
InChIKeyWRFHGDPIDHPWIQ-UHFFFAOYSA-N

SMILES: CCCCC1=NC2(CCCC2)C(=O)N1CC3=CC(=C(C=C3)C4=CC=CC=C4S(=O)(=O)NC5=NOC(=C5C)C)COCC

IUPAC name: 2-[4-[(2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2-(ethoxymethyl)phenyl]-N-(4,5-dimethyl-1,2-oxazol-3-yl)benzenesulfonamide

ChEBI definition: A biphenyl that is 1,1’-biphenyl substituted by (4,5-dimethyl-1,2-oxazol-3-yl)aminosulfonyl, ethoxymethyl, and (2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl groups at positions 2, 2’ and 4’, respectively. It is a dual antagonist of endothelin and angiotensin II receptors approved for the reduction of proteinuria in adults with primary immunoglobulin A nephropathy at risk of rapid disease progression.

Pharmacological roles (ChEBI): angiotensin receptor antagonist, antihypertensive agent, endothelin A receptor antagonist, nephroprotective agent.

Also known as: Esparsentan, Filspari, PS-433540, PS433540, RE-021, Sparsentan, SPARSENTAN

Patent coverage: 140 distinct patent families (354 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 309 (87%) 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
EDNRAETA receptorAntagonist8.030.1%P25101
AGTR1AT1 receptorAntagonist8.440.4%P30556

Broader ChEMBL bioactivity targets: 2 (assay-derived). Sample: Type-1 angiotensin II receptor, Endothelin-1 receptor.

Bioactivity

ChEMBL activities: 4 potent at pChembl ≥ 5 of 4 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

TargetpChemblTypeValueUnitActivity ID
AGTR19.1Ki0.8nMCHEMBL_ACT_12149691
AGTR19.1Ki0.8nMCHEMBL_ACT_1600042
EDNRA8.03Ki9.3nMCHEMBL_ACT_12149690
EDNRA8.03Ki9.3nMCHEMBL_ACT_1600041

Target pathways

Aggregated over 2 target gene(s): EDNRA, AGTR1.

Top Reactome pathways

11 total, by targets touching each:

PathwayTargetsGenes
Peptide ligand-binding receptors2AGTR1, EDNRA
G alpha (q) signalling events2AGTR1, EDNRA
Signal Transduction1AGTR1
Membrane Trafficking1AGTR1
Signaling by GPCR1AGTR1
Class A/1 (Rhodopsin-like receptors)1AGTR1
GPCR downstream signalling1AGTR1
GPCR ligand binding1AGTR1
Vesicle-mediated transport1AGTR1
Cargo recognition for clathrin-mediated endocytosis1AGTR1
Clathrin-mediated endocytosis1AGTR1

Dominant GO biological processes

GO termTargets
signal transduction2
G protein-coupled receptor signaling pathway2
phospholipase C-activating G protein-coupled receptor signaling pathway2
positive regulation of cytosolic calcium ion concentration2
mitotic cell cycle1
branching involved in blood vessel morphogenesis1
response to hypoxia1
in utero embryonic development1
blood vessel remodeling1
response to amphetamine1
regulation of heart rate1
glomerular filtration1
cardiac chamber formation1
left ventricular cardiac muscle tissue morphogenesis1
atrial cardiac muscle tissue development1

Indications & clinical

Indications

3 indications (1 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
IgA glomerulonephritis4MONDO:0005342EFO:0004194
focal segmental glomerulosclerosis3MONDO:0100313EFO:0004236
hypertensive disorder2MONDO:0005044EFO:0000537

Clinical trials

Total trials: 13.

Phase distribution

PhaseTrials
PHASE27
PHASE32
PHASE12
PHASE41
Not specified1

Top trials by phase / activity

NCTPhaseStatusTitle
NCT07219121PHASE4RECRUITINGSparsentan in Posttransplant Immunoglobulin A Nephropathy or Focal Segmental Glomerulosclerosis
NCT03762850PHASE3ACTIVE_NOT_RECRUITINGA Study of the Effect and Safety of Sparsentan in the Treatment of Patients With IgA Nephropathy
NCT03493685PHASE3COMPLETEDStudy of Sparsentan in Patients With Primary Focal Segmental Glomerulosclerosis (FSGS)
NCT04663204PHASE2ACTIVE_NOT_RECRUITINGA Study of the Safety and Activity of Sparsentan for the Treatment of Incident Patients With Immunoglobulin A Nephropathy
NCT05003986PHASE2RECRUITINGStudy of Sparsentan Treatment in Pediatrics With Proteinuric Glomerular Diseases
NCT05630612PHASE2ACTIVE_NOT_RECRUITINGETA and AT1 Antagonism in ANCA-vasculitis (SPARVASC)
NCT00522925PHASE2COMPLETEDA Trial to Evaluate the Safety and Efficacy of PS433540 to Treat Hypertension
NCT00635232PHASE2COMPLETEDA Study To Evaluate The Dose-Related Efficacy and Safety of PS433540 in Subjects With Hypertension
NCT01613118PHASE2COMPLETEDRandomized, Double-Blind, Safety and Efficacy Study of RE-021 (Sparsentan) in Focal Segmental Glomerulosclerosis
NCT05856760PHASE2COMPLETEDA Study to Investigate Safety and Effect of Sparsentan in Combination With SGLT2 Inhibition in Participants With IgAN
NCT07224776PHASE1NOT_YET_RECRUITINGSparsentan for the Treatment of VEGF Signaling Pathway Inhibitor-Associated Proteinuria
NCT05562362PHASE1COMPLETEDStudy to Evaluate the Pharmacokinetics of Oral Sparsentan Suspension
NCT07555301Not specifiedNOT_YET_RECRUITINGClinical Experience With Sparsentan in Switzerland in IgA Nephropathy

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.

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

MoleculeSourceStatusShared targets
ACYCLOVIRChEMBL + PubChemPhase 4 (approved)AGTR1, EDNRA
BOSENTANChEMBL + PubChemPhase 4 (approved)AGTR1, EDNRA
IRBESARTANChEMBLPhase 4 (approved)AGTR1, EDNRA
NITAZOXANIDEChEMBLPhase 4 (approved)AGTR1, EDNRA
SUNITINIBChEMBLPhase 4 (approved)AGTR1, EDNRA
AfatinibPubChemApprovedAGTR1, EDNRA
ApixabanPubChemApprovedAGTR1, EDNRA
BinimetinibPubChemApprovedAGTR1, EDNRA
chenodiolPubChemApprovedAGTR1, EDNRA
DihydroergotaminePubChemApprovedAGTR1, EDNRA
FidaxomicinPubChemApprovedAGTR1, EDNRA
FulvestrantPubChemApprovedAGTR1, EDNRA
ImipenemPubChemApprovedAGTR1, EDNRA
PropoxyphenePubChemApprovedAGTR1, EDNRA
PyrazinamidePubChemApprovedAGTR1, EDNRA
TafamidisPubChemApprovedAGTR1, EDNRA
CRIZOTINIBChEMBL + PubChemPhase 4 (approved)AGTR1
LOSARTANChEMBL + PubChemPhase 4 (approved)AGTR1
OLMESARTAN MEDOXOMILChEMBL + PubChemPhase 4 (approved)AGTR1
RIFAMPINChEMBL + PubChemPhase 4 (approved)AGTR1
TEGASERODChEMBL + PubChemPhase 4 (approved)AGTR1
ALFACALCIDOLChEMBLPhase 4 (approved)AGTR1
AMBRISENTANChEMBLPhase 4 (approved)EDNRA
AMIODARONEChEMBLPhase 4 (approved)EDNRA
AMITRIPTYLINEChEMBLPhase 4 (approved)AGTR1
ANGIOTENSIN IIChEMBLPhase 4 (approved)AGTR1
APROCITENTANChEMBLPhase 4 (approved)EDNRA
ARIPIPRAZOLEChEMBLPhase 4 (approved)AGTR1
BALSALAZIDEChEMBLPhase 4 (approved)AGTR1
BENZBROMARONEChEMBLPhase 4 (approved)AGTR1
BUTOCONAZOLEChEMBLPhase 4 (approved)AGTR1
CALCITRIOLChEMBLPhase 4 (approved)AGTR1
CANDESARTAN CILEXETILChEMBLPhase 4 (approved)AGTR1
CARVEDILOLChEMBLPhase 4 (approved)AGTR1
CLOTRIMAZOLEChEMBLPhase 4 (approved)AGTR1
DABIGATRAN ETEXILATEChEMBLPhase 4 (approved)AGTR1
DESOGESTRELChEMBLPhase 4 (approved)AGTR1
DISULFIRAMChEMBLPhase 4 (approved)AGTR1
DOFETILIDEChEMBLPhase 4 (approved)AGTR1
DONEPEZILChEMBLPhase 4 (approved)AGTR1
EFAVIRENZChEMBLPhase 4 (approved)AGTR1
ENOXACINChEMBLPhase 4 (approved)EDNRA
EPALRESTATChEMBLPhase 4 (approved)AGTR1
EPROSARTANChEMBLPhase 4 (approved)AGTR1
FELODIPINEChEMBLPhase 4 (approved)AGTR1
FENTICONAZOLEChEMBLPhase 4 (approved)AGTR1
FLUOXETINEChEMBLPhase 4 (approved)EDNRA
GRAMICIDINChEMBLPhase 4 (approved)EDNRA
GUAIFENESINChEMBLPhase 4 (approved)AGTR1
HALOPERIDOLChEMBLPhase 4 (approved)AGTR1
IBANDRONIC ACIDChEMBLPhase 4 (approved)AGTR1
INDOCYANINE GREEN ACID FORMChEMBLPhase 4 (approved)AGTR1
IVACAFTORChEMBLPhase 4 (approved)AGTR1
LEFLUNOMIDEChEMBLPhase 4 (approved)AGTR1
LOVASTATINChEMBLPhase 4 (approved)AGTR1
MACITENTANChEMBLPhase 4 (approved)EDNRA
MELOXICAMChEMBLPhase 4 (approved)EDNRA
MILTEFOSINEChEMBLPhase 4 (approved)AGTR1
NIFEDIPINEChEMBLPhase 4 (approved)AGTR1
NIMESULIDEChEMBLPhase 4 (approved)AGTR1

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 29

This page pulls from 29 datasets indexed by BioBTree:

chebichembl_activitychembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsdepmapefoensemblentrezgogoparentgtopdbgtopdb_interactiongtopdb_ligandhgncmondomsigdbpatent_compoundpharmgkbpharmgkb_guidelinepubchempubchem_activityreactomereactomeparentrefseqtranscriptuniprot