Sivelestat

Summary

Sivelestat (CHEMBL76688) is a phase-3 clinical-stage small molecule targeting ELANE; indicated across 2 conditions including heart disorder.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 1 (ELANE)
• Indications: 2 conditions
• Clinical trials: 8
• Chemistry: 434.5 Da · C20H22N2O7S

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL76688
Name	Sivelestat
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	107706
Molecular formula	C20H22N2O7S
Molecular weight	434.5
InChIKey	BTGNGJJLZOIYID-UHFFFAOYSA-N

SMILES: CC(C)(C)C(=O)OC1=CC=C(C=C1)S(=O)(=O)NC2=CC=CC=C2C(=O)NCC(=O)O

IUPAC name: 2-[[2-[[4-(2,2-dimethylpropanoyloxy)phenyl]sulfonylamino]benzoyl]amino]acetic acid

Also known as: LY-544349, LY544349, ONO-5046, Sivelestat, SIVELESTAT, sivelestat, SID174006339, US9073833, Sivelestat (sodium tetrahydrate), Sivelastat

Parent form; salt/anhydrous children: CHEMBL2107493, CHEMBL3182314

Patent coverage: 509 distinct patent families (1,769 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 1,759 (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).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
ELANE	elastase, neutrophil expressed	Inhibition	7.4	0.1%	P08246

Broader ChEMBL bioactivity targets: 5 (assay-derived). Sample: Pancreatic elastase, Neutrophil elastase, Myeloblastin, Prolyl endopeptidase FAP, Neutrophil elastase.

Bioactivity

ChEMBL activities: 23 potent at pChembl ≥ 5 of 25 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
ELANE	8.46	IC50	3.5	nM	CHEMBL_ACT_25047283
ELANE	8	IC50	10	nM	CHEMBL_ACT_13849555
ELANE	7.62	Ki	24	nM	CHEMBL_ACT_24506157
ELANE	7.43	Ki	37	nM	CHEMBL_ACT_18707912
ELANE	7.39	IC50	40.97	nM	CHEMBL_ACT_26035320
ELANE	7.36	IC50	44	nM	CHEMBL_ACT_1109364
ELANE	7.36	IC50	44	nM	CHEMBL_ACT_22398015
ELANE	7.36	IC50	44	nM	CHEMBL_ACT_25718697
ELANE	7.36	IC50	44	nM	CHEMBL_ACT_6301194
ELANE	7.36	IC50	44	nM	CHEMBL_ACT_654828
ELANE	7.3	IC50	50	nM	CHEMBL_ACT_17690661
ELANE	7.3	IC50	50	nM	CHEMBL_ACT_22437815
ELANE	7.16	IC50	70	nM	CHEMBL_ACT_15159044
ELANE	6.89	IC50	128	nM	CHEMBL_ACT_25047299
ELANE	6.87	IC50	136	nM	CHEMBL_ACT_12674706
Q3UP87	6.84	IC50	145.4	nM	CHEMBL_ACT_15159160
ELANE	6.7	Ki	200	nM	CHEMBL_ACT_22398016
ELANE	6.7	Ki	200	nM	CHEMBL_ACT_654827
PRTN3	6.47	IC50	340	nM	CHEMBL_ACT_15159070
FAP	6.23	Ki	590	nM	CHEMBL_ACT_29108086
ELANE	6.15	IC50	704	nM	CHEMBL_ACT_24392858
FAP	5.89	IC50	1300	nM	CHEMBL_ACT_29108103
P00772	5.66	IC50	2185	nM	CHEMBL_ACT_15159162

Target pathways

Aggregated over 1 target gene(s): ELANE.

Top Reactome pathways

8 total, by targets touching each:

Pathway	Targets	Genes
Collagen degradation	1	ELANE
Degradation of the extracellular matrix	1	ELANE
Activation of Matrix Metalloproteinases	1	ELANE
Pyroptosis	1	ELANE
Neutrophil degranulation	1	ELANE
Antimicrobial peptides	1	ELANE
Regulation of Complement cascade	1	ELANE
Expression of NOTCH2NL genes	1	ELANE

Dominant GO biological processes

GO term	Targets
negative regulation of transcription by RNA polymerase II	1
response to yeast	1
acute inflammatory response to antigenic stimulus	1
leukocyte migration involved in inflammatory response	1
biosynthetic process of antibacterial peptides active against Gram-negative bacteria	1
proteolysis	1
intracellular calcium ion homeostasis	1
phagocytosis	1
response to UV	1
extracellular matrix disassembly	1
protein catabolic process	1
response to lipopolysaccharide	1
negative regulation of chemokine production	1
negative regulation of interleukin-8 production	1
positive regulation of interleukin-8 production	1

Indications & clinical

Indications

2 indications (0 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).

Indication	Trial phase	MONDO	EFO
heart disorder	3	MONDO:0005267	EFO:0003777

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

Clinical trials

Total trials: 8.

Phase distribution

Phase	Trials
Not specified	4
PHASE2	2
PHASE3	1
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06276569	PHASE3	COMPLETED	Efficacy and Safety of Sivelestat in Preventing Postoperative Acute Lung Injury or Acute Respiratory Distress Syndrome After Cardiac Surgery
NCT06381661	PHASE2	NOT_YET_RECRUITING	Adaptive Platform Trial for Personnalisation of Sepsis Treatment in Children and Adults: a Multi-national, Treatable Traits-guided, Adaptive, Exploratory, Bayesian Basket Trial
NCT07118930	PHASE2	RECRUITING	Study of Sivelestat Sodium in OPCABG
NCT00036062	PHASE1/PHASE2	COMPLETED	A Phase II Study to Determine the Efficacy and Safety of Sivelestat in Subjects With Acute Lung Injury
NCT06195267	Not specified	RECRUITING	Protective Effect of Sivelestat Against Negative Pulmonary Function and Organ Dysfunction After Cardiovascular Surgery (PANDA VI)
NCT06387823	Not specified	RECRUITING	Efficacy and Safety of Sivelestat Sodium and Dexamethasone in the Treatment of ARDS
NCT05874700	Not specified	UNKNOWN	A Pilot Study of Sivelestat Sodium to Shorten Mechanical Ventilation in Acute Aortic Dissection
NCT07196605	Not specified	COMPLETED	Sodium Sivelestat With Mechanical Thrombectomy for Acute Stroke: A Pilot Study

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

Related molecules

Related molecules

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.

10 molecules share ≥1 primary target. Top 10 by shared-target count:

Molecule	Source	Status	Shared targets
BOCEPREVIR	ChEMBL	Phase 4 (approved)	ELANE
BORTEZOMIB	ChEMBL	Phase 4 (approved)	ELANE
TELAPREVIR	ChEMBL	Phase 4 (approved)	ELANE
EPIGALOCATECHIN GALLATE	ChEMBL	Phase 3	ELANE
QUERCETIN	ChEMBL	Phase 3	ELANE
ALVELESTAT	ChEMBL	Phase 2	ELANE
DELANZOMIB	ChEMBL	Phase 2	ELANE
FRESELESTAT	ChEMBL	Phase 2	ELANE
LUTEOLIN	ChEMBL	Phase 2	ELANE
MIDESTEINE	ChEMBL	Phase 2	ELANE