ELANE

Summary

ELANE (elastase, neutrophil expressed, HGNC:3309) is a protein-coding gene on chromosome 19p13.3, encoding Neutrophil elastase (P08246). Serine protease that modifies the functions of natural killer cells, monocytes and granulocytes.

Elastases form a subfamily of serine proteases that hydrolyze many proteins in addition to elastin. Humans have six elastase genes which encode structurally similar proteins. The encoded preproprotein is proteolytically processed to generate the active protease. Following activation, this protease hydrolyzes proteins within specialized neutrophil lysosomes, called azurophil granules, as well as proteins of the extracellular matrix. The enzyme may play a role in degenerative and inflammatory diseases through proteolysis of collagen-IV and elastin. This protein also degrades the outer membrane protein A (OmpA) of E. coli as well as the virulence factors of such bacteria as Shigella, Salmonella and Yersinia. Mutations in this gene are associated with cyclic neutropenia and severe congenital neutropenia (SCN). This gene is present in a gene cluster on chromosome 19.

Source: NCBI Gene 1991 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neutropenia (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 908 total — 44 pathogenic, 56 likely-pathogenic
• Phenotypes (HPO): 64
• Druggable target: yes — 11 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001972

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3309
Approved symbol	ELANE
Name	elastase, neutrophil expressed
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	NE, HNE, HLE, PMN-E
Ensembl gene	ENSG00000197561
Ensembl biotype	protein_coding
OMIM	130130
Entrez	1991

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000263621, ENST00000590230, ENST00000958526

RefSeq mRNA: 1 — MANE Select: NM_001972 NM_001972

CCDS: CCDS12045

Canonical transcript exons

ENST00000263621 — 5 exons

Exon	Start	End
ENSE00000892229	852303	852395
ENSE00000892230	855958	856243
ENSE00003889691	852876	853032
ENSE00003895551	855564	855794
ENSE00003896037	853262	853403

Expression profiles

Bgee: expression breadth ubiquitous, 124 present calls, max score 99.31.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 93.9664 / max 60511.3017, expressed in 182 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
172790	93.2987	90
172792	0.1546	19
172787	0.1153	17
172793	0.0961	7
172789	0.0766	42
172788	0.0623	24
208624	0.0508	20
172795	0.0355	4
172794	0.0344	7
172796	0.0228	6

Top tissues by expression

134 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
bone marrow	UBERON:0002371	99.31	gold quality
bone marrow cell	CL:0002092	98.82	gold quality
monocyte	CL:0000576	87.65	gold quality
leukocyte	CL:0000738	86.37	gold quality
blood	UBERON:0000178	85.20	gold quality
spleen	UBERON:0002106	81.37	gold quality
granulocyte	CL:0000094	78.86	gold quality
right lung	UBERON:0002167	76.22	gold quality
vastus lateralis	UBERON:0001379	75.80	gold quality
apex of heart	UBERON:0002098	73.95	gold quality
mucosa of stomach	UBERON:0001199	71.84	gold quality
upper lobe of left lung	UBERON:0008952	69.91	gold quality
right atrium auricular region	UBERON:0006631	69.41	gold quality
subcutaneous adipose tissue	UBERON:0002190	69.08	gold quality
adipose tissue	UBERON:0001013	68.37	gold quality
omental fat pad	UBERON:0010414	67.72	gold quality
skin of abdomen	UBERON:0001416	67.58	gold quality
heart left ventricle	UBERON:0002084	67.38	gold quality
lower esophagus muscularis layer	UBERON:0035833	67.31	gold quality
lower esophagus	UBERON:0013473	67.19	gold quality
right lobe of thyroid gland	UBERON:0001119	67.08	gold quality
zone of skin	UBERON:0000014	67.04	gold quality
skin of leg	UBERON:0001511	66.95	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	66.87	gold quality
left lobe of thyroid gland	UBERON:0001120	66.10	gold quality
heart	UBERON:0000948	65.05	gold quality
left uterine tube	UBERON:0001303	64.60	gold quality
thoracic mammary gland	UBERON:0005200	64.55	gold quality
thyroid gland	UBERON:0002046	64.33	gold quality
gastrocnemius	UBERON:0001388	63.93	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-GEOD-89232	yes	9564.45
E-HCAD-6	yes	2471.09
E-MTAB-9801	yes	1477.70
E-HCAD-4	yes	1135.40
E-HCAD-9	yes	965.33
E-MTAB-9067	yes	15.24
E-CURD-122	yes	12.29
E-ANND-3	yes	7.64

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF4, CEBPA, CEBPB, CEBPD, CEBPE, CEBPG, ETS1, GABPA, GFI1, LEF1, MYB, NFE2L2, RUNX1, RUNX2, RUNX3, SP1, SPI1, TBP

Literature-anchored findings (GeneRIF, showing 40)

• Mutant neutrophil elastase induces accelerated apoptosis of promyelocytes, leading to maturation arrest in congenital and cyclic neutropenia. (PMID:11846296)
• UVA light stimulates the production of neutrophil elastase by dermal fibroblasts: a possible contribution to the remodeling of elastotic areas in sun-damaged skin. (PMID:11928814)
• Elastase is mainly responsible for cartilage damage by stimulated human neutrophils, as demonstrated by the use of selective elastase inhibitors. (PMID:12020136)
• Neutrophil elastase-induced overexpression of mucin genes in cultured tumor cells is inhibited by a retinoic acid receptor alpha antagonist. (PMID:12042033)
• degraded scu-PA and also tcu-PA, t-PA and plasmin, resulting in loss of fibrinolytic activity (PMID:12083479)
• Precursor cells containing the ELA2 mutation are selectively lost during myelopoiesis or fail to develop into neutrophils, confirming the pathogenic nature of elastase mutations in humans. (PMID:12091371)
• HNE plays a role in neutrophil response to inflammation (PMID:12114510)
• plasma levels are increased during G-CSF induced hematopoietic stem cell mobilization (PMID:12183836)
• Treatment of human gingival fibroblasts with human leukocyte elastase down-regulated CD40 expression & binding to CD40 ligand. CD40 reduction by direct proteolysis by HLE was seen in skin & lung fibroblasts (not monocytes, macrophages, & dendritic cells). (PMID:12223522)
• Neutrophil elastase plays a role in providing negative feedback to granulopoiesis by direct antagonism of G-CSF. (PMID:12393522)
• Protease entry results in direct cleavage of p65 NF-kappaB in the N-terminal region by PR3 and in the C-terminal region by HNE. PR3 and HNE have specific, fundamental roles in endothelial responses during inflammation. (PMID:12444202)
• REVIEW: role of ela2 germline mutations in inherited neutropenia, gene feedback circuits, signalling genetics, and proposal that neutrophil elastase acts as an inhibitor of myelopoiesis (PMID:12483111)
• adherent PMNs induce a localized, sequential disassembly of endothelial adherens junctions, which is partially mediated by PMN-derived elastase (PMID:12700588)
• Review. Heterozygous mutations in the ELA2 gene have been described in cyclical & congenital neutropenia. A case of paternal mosaicism has provided genetic “proof” of the pathogenicity of such mutations. (PMID:12745650)
• Fibrous and atheromatous plaques but not normal arteries contained NE; NE abounded in the macrophage-rich shoulders of atheromatous plaques with features of vulnerability. Neutrophil elastase and macrophages colocalized in such vulnerable plaques (PMID:12771009)
• Mutations in proto-oncogene GFI1 cause human neutropenia and target ELA2 (PMID:12778173)
• Neutrophil elastase up-regulates interleukin-8 via toll-like receptor 4 (PMID:12782302)
• Multimeric SFTPD was partially digested by ELA2 dose- and time-dependently with loss of its carbohydrate recognition domain. (PMID:12853121)
• in vitro challenge of neutrophils in asthmatic patients with allergens to which the patients were sensitive elicited a release of elastase by these cells. The in vitro activation of neutrophils was highly allergen specific. (PMID:12876407)
• the effect of kininogen degradation by human neutrophil elastase (HNE) on kinin generation (PMID:12887060)
• elastase overproduction by the leukemic clone can change the growth environment by digesting growth factors, thereby giving advantage to Ph+ hematopoiesis (PMID:12893759)
• NE levels in infected lobes were higher than those in uninvolved lobes, and NE levels were significantly elevated in both, compared with that in control lobes in community acquired pneumonia (PMID:12934194)
• NE-induced degradation of G-CSG and G-CSFR correlates with a reduction in the biologic activity of the cytokine and a decrease in the signaling function of the receptor because of decreased G-CSFR surface expression. (PMID:14587040)
• Since NE is maximally produced in promyelocytes, this protease may play a role in APL pathogenesis by facilitating the leukemogenic potential of PML-RARalpha (PMID:14636558)
• Serine proteinases neutrophil elastase and cathepsin G cooperate for the proteolytic regulation of CD87/urokinase receptor on monocytic cells. (PMID:14688365)
• An important part of the antimicrobial mechanism of neutrophil elastase may be a periplasmic bacteriostatic effect of protease that has translocated across the damaged outer membrane. (PMID:14705961)
• Results indicate that neutrophil elastase activates p38 MAP kinase which upregulates NF-kappaB and AP-1 activities, thus inducing interleukin-8 mRNA expression and protein synthesis. (PMID:14730209)
• the expression of neutropenia in cyclic and severe congenital neutropenia may be either homogeneous or variable according to the type of mutations, suggesting different pathogenetic mechanisms. (PMID:14962902)
• Results demonstrate that human neutrophil elastase is mitogenic for airway smooth muscle cells by increasing cyclin D1 activity through the mitogen-activated protein kinase signaling pathway. (PMID:15010259)
• neutrophil elastase mutations play a role in human hereditary neutropenia, as shown in a dog model [review] (PMID:15059607)
• neutrophil elastase and cathepsin G are inhibited by PAI-1 mutants (PMID:15131125)
• Release of human leukocyte elastase from neutrophils specifically down-regulates the responsiveness of neutrophils to C5a, and this effect may play a role in the down-regulation of acute inflammation. (PMID:15140022)
• elastase released by polymorphonuclear leukocytes trapped within the mural thrombus impairs the spontaneous anchorage of mesenchymal cells to a fibrin matrix (PMID:15161642)
• secreted E coliO78 OmpA can play a role in protection of bacteria from NE by competitive inhibition (PMID:15595387)
• Neutrophil elastase has a role in PML-retinoic acid receptor alpha activities in early myeloid cells (PMID:15601827)
• Neutrophil elastase, MIP-2, and TLR-4 have roles in progression of human sepsis and murine peritonitis (PMID:15614130)
• data suggest mechanisms by which NE mutations cause neutropenia and suggest that abnormal protein trafficking and accelerated apoptosis of differentiating myeloid cells contribute to the severe congenital neutropenia phenotype of the G185R mutation. (PMID:15657182)
• elastase binds to the beta(2)-integrin CD11b and induces a conformational alteration of CD11b (PMID:15718918)
• human AML cells constitutively secrete and express SDF-1-dependent cell-surface elastase, which regulates their migration and proliferation (PMID:15941909)
• Patients with cyclic neutropenia and agranulocytosis showed mutations in this enzyme. (PMID:16079102)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Elane	ENSMUSG00000020125
rattus_norvegicus	Elane	ENSRNOG00000033685

Paralogs (6): CELA1 (ENSG00000139610), CELA2A (ENSG00000142615), CELA3A (ENSG00000142789), PRTN3 (ENSG00000196415), CELA2B (ENSG00000215704), CELA3B (ENSG00000219073)

Protein

Protein identifiers

Neutrophil elastase — P08246 (reviewed: P08246)

Alternative names: Bone marrow serine protease, Elastase-2, Human leukocyte elastase, Medullasin, PMN elastase

All UniProt accessions (1): P08246

UniProt curated annotations — full annotation on UniProt →

Function. Serine protease that modifies the functions of natural killer cells, monocytes and granulocytes. Inhibits C5a-dependent neutrophil enzyme release and chemotaxis. Promotes cleavage of GSDMB, thereby inhibiting pyroptosis. Promotes blood coagulation. Through the activation of the platelet fibrinogen receptor integrin alpha-IIb/beta-3, potentiates platelet aggregation induced by a threshold concentration of cathepsin G (CTSG). Cleaves and thus inactivates tissue factor pathway inhibitor (TFPI). Capable of killing E.coli but not S.aureus in vitro; digests outer membrane protein A (ompA) in E.coli and K.pneumoniae.

Subunit / interactions. Interacts with NOTCH2NL. Interacts with agaphelin, an antihemostatic protein from Anopheles gambiae.

Subcellular location. Cytoplasmic vesicle. Phagosome.

Tissue specificity. Bone marrow cells. Neutrophil.

Disease relevance. Cyclic haematopoiesis (CH) [MIM:162800] Autosomal dominant disease in which blood-cell production from the bone marrow oscillates with 21-day periodicity. Circulating neutrophils vary between almost normal numbers and zero. During intervals of neutropenia, affected individuals are at risk for opportunistic infection. Monocytes, platelets, lymphocytes and reticulocytes also cycle with the same frequency. The disease is caused by variants affecting the gene represented in this entry. Neutropenia, severe congenital 1, autosomal dominant (SCN1) [MIM:202700] A disorder of hematopoiesis characterized by maturation arrest of granulopoiesis at the level of promyelocytes with peripheral blood absolute neutrophil counts below 0.5 x 10(9)/l and early onset of severe bacterial infections. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the peptidase S1 family. Elastase subfamily.

RefSeq proteins (1): NP_001963* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001254	Trypsin_dom	Domain
IPR001314	Peptidase_S1A	Family
IPR009003	Peptidase_S1_PA	Homologous_superfamily
IPR018114	TRYPSIN_HIS	Active_site
IPR033116	TRYPSIN_SER	Active_site
IPR043504
IPR050850	Peptidase_S1_Elastase_sf	Family

Pfam: PF00089

Enzyme classification (BRENDA):

• EC 3.4.21.37 — leukocyte elastase (BRENDA: 12 organisms, 316 substrates, 1178 inhibitors, 60 Km, 55 kcat entries)

Substrate kinetics (BRENDA)

29 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
N-METHOXYSUCCINYL-ALA-ALA-PRO-VAL-4-NITROANILIDE	0.06–5.02	8
METHOXYSUCCINYL-ALA-ALA-PRO-VAL-4-NITROANILIDE	0.05–1.82	7
N-SUCCINYL-ALA-ALA-ALA 4-NITROANILIDE	1.1–27.8	6
TOSYL-ALA-3-HYDROXY-5-PHENYLPYRROLE	0.016–0.08	5
BENZYLOXYCARBONYL-ALA-3-HYDROXY-5-PHENYLPYRROLE	0.016–0.022	3
BENZYLOXYCARBONYL-ALA-4-NITROPHENOL	0.046–0.065	3
TERT-BUTYLOXYCARBONYL-ALA-4-NITROPHENYL ESTER	0.02–0.27	3
METHOXYSUCCINYL-ALA-ALA-PRO-MET-4-NITROANILIDE	2.4	2
TOSYL-ALA-4-NITROPHENOL	0.028–0.035	2
ACETYL-ALA-ALA-PRO-VAL-4-NITROANILIDE	0.31	1
HEPARIN-ANTITHROMBIN COMPLEX	0.001	1
METHOXYSUCCINYL-ALA-ALA-PRO-ALA-4-NITROANILIDE	0.833	1
METHOXYSUCCINYL-ALA-ALA-PRO-ALA-THIOBENZYL ESTER	0.013	1
METHOXYSUCCINYL-ALA-ALA-PRO-VAL-THIOBENZYL ESTER	0.0023	1
METHOXYSUCCINYL-ALA-ILE-PRO-MET-4-NITROANILIDE	1.7	1

UniProt features (130 total): sequence variant 93, strand 18, disulfide bond 4, helix 4, active site 3, glycosylation site 3, signal peptide 1, propeptide 1, turn 1, chain 1, domain 1

Structure

Experimental structures (PDB)

38 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
9SI4	X-RAY DIFFRACTION	1.14
8VK5	X-RAY DIFFRACTION	1.56
5ABW	X-RAY DIFFRACTION	1.6
4WVP	X-RAY DIFFRACTION	1.63
2Z7F	X-RAY DIFFRACTION	1.7
9ASS	X-RAY DIFFRACTION	1.75
5A0A	X-RAY DIFFRACTION	1.78
1PPF	X-RAY DIFFRACTION	1.8
2RG3	X-RAY DIFFRACTION	1.8
8G25	X-RAY DIFFRACTION	1.8
5A09	X-RAY DIFFRACTION	1.81
8G24	X-RAY DIFFRACTION	1.82
1HNE	X-RAY DIFFRACTION	1.84
4NZL	X-RAY DIFFRACTION	1.85
8G26	X-RAY DIFFRACTION	1.85
3Q76	X-RAY DIFFRACTION	1.86
5A8Y	X-RAY DIFFRACTION	1.9
8D4U	X-RAY DIFFRACTION	1.9
9ASX	X-RAY DIFFRACTION	1.96
3Q77	X-RAY DIFFRACTION	2
1H1B	X-RAY DIFFRACTION	2
5A8Z	X-RAY DIFFRACTION	2
9ATU	X-RAY DIFFRACTION	2.05
5A0C	X-RAY DIFFRACTION	2.1
9ATK	X-RAY DIFFRACTION	2.11
8D4Q	X-RAY DIFFRACTION	2.2
5A0B	X-RAY DIFFRACTION	2.23
5A8X	X-RAY DIFFRACTION	2.23
1PPG	X-RAY DIFFRACTION	2.3
8QGX	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P08246-F1	88.42	0.76

Antibody-complex structures (SAbDab): 1 — 8QGX

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (3): 70 (charge relay system); 117 (charge relay system); 202 (charge relay system)

Disulfide bonds (4): 55–71, 151–208, 181–187, 198–223

Glycosylation sites (3): 88, 124, 173

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-1442490	Collagen degradation
R-HSA-1474228	Degradation of the extracellular matrix
R-HSA-1592389	Activation of Matrix Metalloproteinases
R-HSA-5620971	Pyroptosis
R-HSA-6798695	Neutrophil degranulation
R-HSA-6803157	Antimicrobial peptides
R-HSA-977606	Regulation of Complement cascade
R-HSA-9911233	Expression of NOTCH2NL genes

MSigDB gene sets: 436 (showing top): VERHAAK_AML_WITH_NPM1_MUTATED_DN, REACTOME_SIGNALING_BY_NOTCH, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_INFLAMMATORY_RESPONSE, GOBP_POSITIVE_REGULATION_OF_INTERLEUKIN_8_PRODUCTION, BROWNE_HCMV_INFECTION_8HR_UP, GOCC_SECRETORY_GRANULE, MATTIOLI_MGUS_VS_PCL, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOCC_CELL_SURFACE, GOBP_LEUKOCYTE_MEDIATED_CYTOTOXICITY, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY

GO Biological Process (27): negative regulation of transcription by RNA polymerase II (GO:0000122), response to yeast (GO:0001878), acute inflammatory response to antigenic stimulus (GO:0002438), leukocyte migration involved in inflammatory response (GO:0002523), biosynthetic process of antibacterial peptides active against Gram-negative bacteria (GO:0002812), proteolysis (GO:0006508), intracellular calcium ion homeostasis (GO:0006874), phagocytosis (GO:0006909), response to UV (GO:0009411), extracellular matrix disassembly (GO:0022617), protein catabolic process (GO:0030163), response to lipopolysaccharide (GO:0032496), negative regulation of chemokine production (GO:0032682), negative regulation of interleukin-8 production (GO:0032717), positive regulation of interleukin-8 production (GO:0032757), defense response to bacterium (GO:0042742), positive regulation of MAP kinase activity (GO:0043406), positive regulation of smooth muscle cell proliferation (GO:0048661), negative regulation of inflammatory response (GO:0050728), positive regulation of immune response (GO:0050778), negative regulation of chemotaxis (GO:0050922), pyroptotic inflammatory response (GO:0070269), neutrophil-mediated killing of gram-negative bacterium (GO:0070945), neutrophil-mediated killing of fungus (GO:0070947), positive regulation of leukocyte tethering or rolling (GO:1903238), defense response to fungus (GO:0050832), leukocyte migration (GO:0050900)

GO Molecular Function (10): protease binding (GO:0002020), transcription corepressor activity (GO:0003714), endopeptidase activity (GO:0004175), serine-type endopeptidase activity (GO:0004252), heparin binding (GO:0008201), peptidase activity (GO:0008233), cytokine binding (GO:0019955), protein binding (GO:0005515), serine-type peptidase activity (GO:0008236), hydrolase activity (GO:0016787)

GO Cellular Component (14): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), cytosol (GO:0005829), cell surface (GO:0009986), transcription repressor complex (GO:0017053), secretory granule (GO:0030141), extracellular matrix (GO:0031012), azurophil granule lumen (GO:0035578), specific granule lumen (GO:0035580), phagocytic vesicle (GO:0045335), extracellular exosome (GO:0070062), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Degradation of the extracellular matrix	2
Innate Immune System	2
Extracellular matrix organization	1
Regulated Necrosis	1
Complement cascade	1
Pre-NOTCH Transcription and Translation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cytoplasm	3
negative regulation of DNA-templated transcription	2
inflammatory response	2
protein metabolic process	2
negative regulation of cytokine production	2
interleukin-8 production	2
regulation of interleukin-8 production	2
peptidase activity	2
endomembrane system	2
secretory granule lumen	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
response to fungus	1
inflammatory response to antigenic stimulus	1
acute inflammatory response	1
leukocyte migration	1
antibacterial peptide biosynthetic process	1
defense response to Gram-negative bacterium	1
intracellular monoatomic cation homeostasis	1
calcium ion homeostasis	1
endocytosis	1
response to light stimulus	1
cellular component disassembly	1
extracellular matrix organization	1
macromolecule catabolic process	1
response to molecule of bacterial origin	1
response to lipid	1
response to oxygen-containing compound	1
chemokine production	1
regulation of chemokine production	1
positive regulation of cytokine production	1
defense response	1
response to bacterium	1
MAP kinase activity	1
regulation of MAP kinase activity	1
positive regulation of MAPK cascade	1
positive regulation of protein serine/threonine kinase activity	1
positive regulation of cell population proliferation	1
smooth muscle cell proliferation	1

Protein interactions and networks

STRING

2702 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ELANE	MPO	P05164	999
ELANE	SERPINA1	P01009	999
ELANE	LTF	P02788	996
ELANE	CTSG	P08311	985
ELANE	CAMP	P49913	983
ELANE	SLPI	P03973	981
ELANE	PRTN3	P15637	978
ELANE	MMP9	P14780	973
ELANE	SERPINB1	P30740	963
ELANE	BPI	P17213	897
ELANE	CTSS	P25774	875
ELANE	ELN	P15502	871
ELANE	HMGB1	P09429	869
ELANE	PADI4	Q9UM07	860
ELANE	HAX1	O00165	857

IntAct

28 interactions, top by confidence:

A	B	Type	Score
SERPINA1	ELANE	psi-mi:“MI:0407”(direct interaction)	0.590
ELANE	ITIH2	psi-mi:“MI:0914”(association)	0.530
EGFL8	MPO	psi-mi:“MI:0914”(association)	0.530
SLPI	ELANE	psi-mi:“MI:0407”(direct interaction)	0.440
ELANE	CFP	psi-mi:“MI:0407”(direct interaction)	0.440
ELANE	S	psi-mi:“MI:0570”(protein cleavage)	0.440
	ELANE	psi-mi:“MI:0570”(protein cleavage)	0.440
ELANE	Col17a1	psi-mi:“MI:0570”(protein cleavage)	0.440
	ELANE	psi-mi:“MI:0407”(direct interaction)	0.440
ELANE	GZMB	psi-mi:“MI:0915”(physical association)	0.400
OCRL	LTF	psi-mi:“MI:0914”(association)	0.350
IRAK2	LTF	psi-mi:“MI:0914”(association)	0.350
SRPK1	SNRPGP15	psi-mi:“MI:0914”(association)	0.350
	ENO1	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
GNG8	POTEF	psi-mi:“MI:0914”(association)	0.350
RHBDD1	A2ML1	psi-mi:“MI:0914”(association)	0.350
KLK10	IGLL5	psi-mi:“MI:0914”(association)	0.350
C9orf85	MPO	psi-mi:“MI:0914”(association)	0.350
CACNG4	F13A1	psi-mi:“MI:0914”(association)	0.350
ELANE	SERPINC1	psi-mi:“MI:0914”(association)	0.350
RSRP1	A2ML1	psi-mi:“MI:0914”(association)	0.350
TRIM16L	IGLL5	psi-mi:“MI:0914”(association)	0.350
P/V/C	KPNA3	psi-mi:“MI:0914”(association)	0.350

BioGRID (28): NOTCH2NL (Two-hybrid), NOTCH2NL (Affinity Capture-Western), ELANE (Reconstituted Complex), ELANE (Affinity Capture-MS), ELANE (Co-fractionation), ELANE (Co-fractionation), ELANE (Co-fractionation), SERPINA3 (Biochemical Activity), SERPINF2 (Biochemical Activity), SERPING1 (Biochemical Activity), ELANE (Affinity Capture-MS), MIB2 (Affinity Capture-MS), FKRP (Affinity Capture-MS), ELANE (Affinity Capture-MS), SERPINI1 (Affinity Capture-MS)

ESM2 similar proteins: A7LAC6, A7LAC7, B5U6Y3, B8V7S0, D8MIA2, D8MIA3, E0Y421, E5L0E6, J3RYA3, O13063, O35164, O35453, O73800, O93267, P03953, P05981, P08246, P08884, P09872, P0CG03, P0DJF6, P12323, P17977, P20160, P22457, P28293, P32038, P35034, P47796, P80015, P85109, Q00356, Q05511, Q17004, Q28380, Q3T0A3, Q3UP87, Q5R5E8, Q5W958, Q71QI3

Diamond homologs: A7WPL7, O35164, O35205, O46683, O60259, O88780, P00746, P00759, P00760, P00761, P00762, P00763, P00764, P00770, P00773, P04187, P06868, P06871, P07146, P07647, P08217, P08246, P08311, P08426, P08882, P08883, P08884, P09582, P09650, P10144, P11032, P11033, P11034, P12544, P13366, P15119, P17977, P18291, P19799, P20160

SIGNOR signaling

21 interactions.

A	Effect	B	Mechanism
CEBPA	“up-regulates quantity by expression”	ELANE	“transcriptional regulation”
LEF1	“up-regulates quantity by expression”	ELANE	“transcriptional regulation”
RUNX2	“up-regulates quantity by expression”	ELANE	“transcriptional regulation”
RUNX1	“up-regulates quantity by expression”	ELANE	“transcriptional regulation”
RUNX3	“up-regulates quantity by expression”	ELANE	“transcriptional regulation”
ELANE	“up-regulates activity”	AGT	cleavage
ELANE	“down-regulates activity”	SERPIND1	cleavage
ELANE	“up-regulates activity”	F2R	cleavage
ELANE	“down-regulates activity”	F2R	cleavage
ELANE	“down-regulates activity”	F2RL1	cleavage
ELANE	“up-regulates activity”	F5	cleavage
ELANE	“down-regulates activity”	F5	cleavage

Disease & clinical

Clinical variants and AI predictions

ClinVar

908 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	44
Likely pathogenic	56
Uncertain significance	415
Likely benign	250
Benign	46

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1052483	NM_001972.4(ELANE):c.723G>A (p.Trp241Ter)	Pathogenic
1069597	NM_001972.4(ELANE):c.597+5G>T	Pathogenic
1069598	NM_001972.4(ELANE):c.687del (p.Asp230fs)	Pathogenic
1335314	NM_001972.4(ELANE):c.544del (p.Arg182fs)	Pathogenic
1339552	NM_001972.4(ELANE):c.452G>C (p.Cys151Ser)	Pathogenic
1339651	NM_001972.4(ELANE):c.574_583del (p.Gly192fs)	Pathogenic
1343367	NM_001972.4(ELANE):c.1A>G (p.Met1Val)	Pathogenic
1372707	NM_001972.4(ELANE):c.461T>G (p.Met154Arg)	Pathogenic
1402531	NM_001972.4(ELANE):c.367-8C>A	Pathogenic
1495615	NM_001972.4(ELANE):c.169G>A (p.Ala57Thr)	Pathogenic
16746	NM_001972.4(ELANE):c.211T>C (p.Cys71Arg)	Pathogenic
16748	NM_001972.4(ELANE):c.640G>A (p.Gly214Arg)	Pathogenic
1693275	NM_001972.4(ELANE):c.289_300dup (p.Ala100_Val101insGlnValPheAla)	Pathogenic
1918199	NM_001972.4(ELANE):c.538del (p.Leu180fs)	Pathogenic
208494	NM_001972.4(ELANE):c.561C>A (p.Cys187Ter)	Pathogenic
2138169	NM_001972.4(ELANE):c.197T>G (p.Met66Arg)	Pathogenic
2138170	NM_001972.4(ELANE):c.416C>G (p.Pro139Arg)	Pathogenic
242284	NM_001972.4(ELANE):c.452G>T (p.Cys151Phe)	Pathogenic
242287	NM_001972.4(ELANE):c.597+1G>A	Pathogenic
242289	NM_001972.4(ELANE):c.140T>C (p.Leu47Pro)	Pathogenic
242297	NM_001972.4(ELANE):c.336_359del (p.Asn113_Ile120del)	Pathogenic
245598	NM_001972.4(ELANE):c.597+5G>A	Pathogenic
245599	NM_001972.4(ELANE):c.597+1G>C	Pathogenic
2925630	NM_001972.4(ELANE):c.164G>A (p.Cys55Tyr)	Pathogenic
2942789	NM_001972.4(ELANE):c.639del (p.His213fs)	Pathogenic
2947200	NM_001972.4(ELANE):c.129C>G (p.Phe43Leu)	Pathogenic
372362	NM_001972.4(ELANE):c.137C>T (p.Ser46Phe)	Pathogenic
373070	NM_001972.2(ELANE):c.600_601dupGG	Pathogenic
3759509	NM_001972.4(ELANE):c.597+1G>T	Pathogenic
3771868	NM_001972.4(ELANE):c.179T>C (p.Ile60Thr)	Pathogenic

SpliceAI

1016 predictions. Top by Δscore:

Variant	Effect	Δscore
19:853031:GT:G	donor_gain	1.0000
19:853033:G:GG	donor_gain	1.0000
19:855790:GTTTC:G	donor_gain	1.0000
19:855795:G:GG	donor_gain	1.0000
19:851259:GCA:G	donor_gain	0.9900
19:851262:G:GG	donor_gain	0.9900
19:853030:TGTGT:T	donor_loss	0.9900
19:853033:G:A	donor_loss	0.9900
19:853034:TGA:T	donor_loss	0.9900
19:853036:A:AC	donor_loss	0.9900
19:853256:C:A	acceptor_gain	0.9900
19:853256:CGGCA:C	acceptor_loss	0.9900
19:853257:GGCA:G	acceptor_loss	0.9900
19:853258:GCA:G	acceptor_loss	0.9900
19:853259:CAG:C	acceptor_loss	0.9900
19:853260:A:AG	acceptor_gain	0.9900
19:853260:A:C	acceptor_loss	0.9900
19:853261:G:GG	acceptor_gain	0.9900
19:853261:GA:G	acceptor_gain	0.9900
19:853261:GAA:G	acceptor_gain	0.9900
19:853261:GAAAC:G	acceptor_gain	0.9900
19:853402:AGGTG:A	donor_loss	0.9900
19:853403:GG:G	donor_loss	0.9900
19:853404:G:GG	donor_loss	0.9900
19:853993:G:GT	donor_gain	0.9900
19:853994:G:T	donor_gain	0.9900
19:855556:C:A	acceptor_gain	0.9900
19:855559:CACA:C	acceptor_loss	0.9900
19:855562:A:AC	acceptor_loss	0.9900
19:855562:A:AG	acceptor_gain	0.9900

AlphaMissense

1705 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:855665:G:C	W156C	0.999
19:855665:G:T	W156C	0.999
19:853387:A:C	D117A	0.998
19:853387:A:T	D117V	0.998
19:853386:G:C	D117H	0.996
19:853387:A:G	D117G	0.996
19:856083:G:C	W241C	0.996
19:856083:G:T	W241C	0.996
19:853002:T:A	V65D	0.995
19:855650:C:G	C151W	0.995
19:855962:A:T	D201V	0.995
19:856054:T:C	F232L	0.995
19:856056:T:A	F232L	0.995
19:856056:T:G	F232L	0.995
19:852935:T:C	F43L	0.994
19:852937:C:A	F43L	0.994
19:852937:C:G	F43L	0.994
19:853386:G:T	D117Y	0.994
19:855660:G:T	G155C	0.994
19:855666:G:T	G157C	0.994
19:855967:G:T	G203C	0.994
19:855970:A:C	S204R	0.994
19:855972:C:A	S204R	0.994
19:855972:C:G	S204R	0.994
19:856055:T:G	F232C	0.994
19:852972:G:A	C55Y	0.993
19:853020:G:A	C71Y	0.993
19:855962:A:C	D201A	0.993
19:855968:G:T	G203V	0.993
19:856012:T:C	F218L	0.993

dbSNP variants (sampled 300 via entrez): RS1000290721 (19:853407 C>T), RS1000641220 (19:853164 C>G,T), RS1001030002 (19:852590 GGGGA>G), RS1001394472 (19:852242 G>A), RS1002148179 (19:853086 A>C,G,T), RS1002179256 (19:852820 G>A,C,T), RS1002465026 (19:855900 G>A,C,T), RS1002488420 (19:850402 TG>T), RS1002637859 (19:851180 G>A), RS1002848956 (19:855077 T>C), RS1003203721 (19:854862 A>G), RS1003714799 (19:853630 C>T), RS1004221551 (19:850543 C>A), RS1004780968 (19:852926 G>A,C), RS1005041908 (19:854628 G>A,C)

Disease associations

OMIM: gene MIM:130130 | disease phenotypes: MIM:162800, MIM:202700, MIM:300299

GenCC curated gene-disease

Disease	Classification	Inheritance
neutropenia	Definitive	Autosomal dominant
cyclic hematopoiesis	Strong	Autosomal dominant
autosomal dominant severe congenital neutropenia	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
neutropenia	Definitive	AD

Mondo (7): cyclic hematopoiesis (MONDO:0008090), neutropenia, severe congenital, 1, autosomal dominant (MONDO:0042490), autoinflammatory syndrome (MONDO:0019751), neutropenia (MONDO:0001475), X-linked severe congenital neutropenia (MONDO:0010294), autosomal dominant severe congenital neutropenia (MONDO:0008742), hereditary angioedema with normal C1Inh (MONDO:0100567)

Orphanet (5): Cyclic neutropenia (Orphanet:2686), Autoinflammatory syndrome (Orphanet:93665), X-linked severe congenital neutropenia (Orphanet:86788), Autosomal dominant severe congenital neutropenia (Orphanet:486), Hereditary angioedema with normal C1Inh (Orphanet:528647)

HPO phenotypes

64 total (30 of 64 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000155	Oral ulcer
HP:0000230	Gingivitis
HP:0000246	Sinusitis
HP:0000388	Otitis media
HP:0000704	Periodontitis
HP:0000938	Osteopenia
HP:0001028	Hemangioma
HP:0001507	Growth abnormality
HP:0001581	Recurrent skin infections
HP:0001873	Thrombocytopenia
HP:0001875	Decreased total neutrophil count
HP:0001880	Increased total eosinophil count
HP:0001888	Decreased total lymphocyte count
HP:0001894	Thrombocytosis
HP:0001903	Anemia
HP:0001909	Leukemia
HP:0001915	Aplastic anemia
HP:0001945	Fever
HP:0001954	Recurrent fever
HP:0002014	Diarrhea
HP:0002027	Abdominal pain
HP:0002090	Pneumonia
HP:0002315	Headache
HP:0002586	Peritonitis
HP:0002653	Bone pain
HP:0002716	Lymphadenopathy
HP:0002718	Recurrent bacterial infections
HP:0002863	Myelodysplasia
HP:0003453	Antineutrophil antibody positivity

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006585_2698	Blood protein levels	2.000000e-06

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D009503	Neutropenia	C15.378.243.750.184.564; C15.378.553.546.184.564
C536227	Cyclic neutropenia (supp.)
C565969	Neutropenia, Severe Congenital, Autosomal Dominant 1 (supp.)
C564539	Neutropenia, Severe Congenital, X-Linked (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL248 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

11 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 144,205 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL218394	BOCEPREVIR	4	2,760
CHEMBL231813	TELAPREVIR	4	3,301
CHEMBL325041	BORTEZOMIB	4	13,120
CHEMBL297453	EPIGALOCATECHIN GALLATE	3	22,804
CHEMBL50	QUERCETIN	3	74,559
CHEMBL76688	SIVELESTAT	3	1,769
CHEMBL151	LUTEOLIN	2	23,523
CHEMBL1808549	MIDESTEINE	2	183
CHEMBL25892	FRESELESTAT	2	43
CHEMBL270515	DELANZOMIB	2	1,883
CHEMBL3617964	ALVELESTAT	2	260

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — S1: Chymotrypsin

Most potent curated ligand interactions (7 total), top 7:

Ligand	Action	Affinity	Parameter
alvelestat	Inhibition	8.0	pKi
BAY-678	Inhibition	7.82	pKi
CHF6333	Inhibition	7.7	pIC50
sivelestat	Inhibition	7.4	pIC50
compound 10l [PMID: 24556381]	Inhibition	6.2	pIC50
compound 10f [PMID: 24556381]	Inhibition	5.37	pIC50
compound 4g [PMID: 22595175]	Inhibition	4.99	pIC50

Binding affinities (BindingDB)

978 measured of 1373 human assays (1399 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
5-[2-(4-cyanophenyl)pyrazol-3-yl]-N-[3-[[5-[2-(4-cyanophenyl)pyrazol-3-yl]-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]pyridine-3-carbonyl]amino]-2-hydroxypropyl]-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]pyridine-3-carboxamide	IC50	0.011 nM	US-12415819: Cu- and Ni-catalyzed decarboxylative borylation reactions
2-[[4-[[(2S)-1-[(2S)-2-[[(1R)-1-borono-2-methylpropyl]carbamoyl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]carbamoyl]benzoyl]amino]acetic acid	IC50	0.015 nM	US-12415819: Cu- and Ni-catalyzed decarboxylative borylation reactions
[(1R)-1-[[(2S)-1-[(2S)-2-[[4-[(4-chlorophenyl)sulfonylcarbamoyl]benzoyl]amino]-3-methylbutanoyl]pyrrolidine-2-carbonyl]amino]-2-methylpropyl]boronic acid	IC50	0.03 nM	US-12415819: Cu- and Ni-catalyzed decarboxylative borylation reactions
POL6014	IC50	0.093 nM	US-12415819: Cu- and Ni-catalyzed decarboxylative borylation reactions
4-[(6R)-5-isocyano-4-methyl-2-oxo-3-[3-(trifluoromethyl)phenyl]-1,6-dihydropyrimidin-6-yl]-3-[(S)-methylsulfinyl]benzonitrile	IC50	0.3 nM	US-9174997: 4-(4-cyano-2-thioaryl)dihydropyrimidinones and use thereof
2-[5-acetyl-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-4H-pyrimidin-4-yl]-5-cyano-N-methyl-N-(pyrazolidin-4-ylmethyl)benzamide	IC50	0.3 nM	US-9290457: Substituted dihydropyrimidinones and their use as inhibitors of neutrophil elastase activity
2-[(4R)-4-(4-cyano-2-methylsulfonylphenyl)-5-isocyano-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-4H-pyrimidin-3-yl]acetamide	IC50	0.45 nM	US-9174997: 4-(4-cyano-2-thioaryl)dihydropyrimidinones and use thereof
4-[(6R)-5-isocyano-4-methyl-2-oxo-3-[3-(trifluoromethyl)phenyl]-1,6-dihydropyrimidin-6-yl]-3-methylsulfonylbenzonitrile	IC50	0.5 nM	US-9174997: 4-(4-cyano-2-thioaryl)dihydropyrimidinones and use thereof
4-oxo-β-lactam (3)	KI	0.63 nM
2,6-Dichloro-benzoic acid 3,3,5-trioxo-3lambda6-thia-4-aza-tricyclo[5.2.1.02,6]dec-2(6)-en-4-ylmethyl ester	KI	0.8 nM
4-[(4R)-5-isocyano-6-methyl-2-oxo-3-(4-pyridin-2-ylpiperazine-1-carbonyl)-1-[3-(trifluoromethyl)phenyl]-4H-pyrimidin-4-yl]-3-methylsulfonylbenzonitrile	IC50	0.9 nM	US-9174997: 4-(4-cyano-2-thioaryl)dihydropyrimidinones and use thereof
3-[[2-[5-(4-cyanophenyl)-6-methoxycarbonyl-7-methyl-3-oxo-8-[3-(trifluoromethyl)phenyl]-5H-[1,2,4]triazolo[4,3-a]pyrimidin-2-yl]acetyl]-methylamino]propyl-trimethylazanium	IC50	0.99 nM	US-12415819: Cu- and Ni-catalyzed decarboxylative borylation reactions
4-(4-cyano-2-methoxyphenyl)-N-ethyl-2,5-dioxo-1-[3-(trifluoromethyl)phenyl]-6,7-dihydro-4H-cyclopenta[d]pyrimidine-3-carboxamide	IC50	1 nM	US-9670166: Substituted bicyclic dihydropyrimidinones and their use as inhibitors of neutrophil elastase activity
2-[5-acetyl-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-4H-pyrimidin-4-yl]-N-(1-bicyclo[1.1.1]pentanyl)-5-cyanobenzamide	IC50	1 nM	US-9290457: Substituted dihydropyrimidinones and their use as inhibitors of neutrophil elastase activity
2-[5-acetyl-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-4H-pyrimidin-4-yl]-N-benzyl-5-cyanobenzamide	IC50	1 nM	US-9290457: Substituted dihydropyrimidinones and their use as inhibitors of neutrophil elastase activity
ethyl 4-[4-cyano-2-[2-methoxyethyl(methyl)carbamoyl]phenyl]-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-4H-pyrimidine-5-carboxylate	IC50	1 nM	US-9290457: Substituted dihydropyrimidinones and their use as inhibitors of neutrophil elastase activity
ethyl 4-[4-cyano-2-[(1-methylpiperidin-4-yl)carbamoyl]phenyl]-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-4H-pyrimidine-5-carboxylate	IC50	1 nM	US-9290457: Substituted dihydropyrimidinones and their use as inhibitors of neutrophil elastase activity
ethyl 4-[4-cyano-2-[(1,1-dioxothiolan-3-yl)carbamoyl]phenyl]-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-4H-pyrimidine-5-carboxylate	IC50	1 nM	US-9290457: Substituted dihydropyrimidinones and their use as inhibitors of neutrophil elastase activity
ethyl 4-[4-cyano-2-[(3S)-3-(dimethylamino)pyrrolidine-1-carbonyl]phenyl]-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-4H-pyrimidine-5-carboxylate	IC50	1 nM	US-9290457: Substituted dihydropyrimidinones and their use as inhibitors of neutrophil elastase activity
ethyl 4-[4-cyano-2-[(2-morpholin-4-yl-2-oxoethyl)carbamoyl]phenyl]-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-4H-pyrimidine-5-carboxylate	IC50	1 nM	US-9290457: Substituted dihydropyrimidinones and their use as inhibitors of neutrophil elastase activity
4-(4-cyanophenyl)-N-[2-(dimethylamino)ethyl]-2,5-dioxo-1-[3-(trifluoromethyl)phenyl]-6,7-dihydro-4H-cyclopenta[d]pyrimidine-3-carboxamide	EC50	1 nM	US-9290459: Substituted bicyclic dihydropyrimidinones and their use as inhibitors of neutrophil elastase activity
4-(4-cyanophenyl)-N-(2-methylsulfinylethyl)-2,5-dioxo-1-[3-(trifluoromethyl)phenyl]-6,7-dihydro-4H-cyclopenta[d]pyrimidine-3-carboxamide	EC50	1 nM	US-9290459: Substituted bicyclic dihydropyrimidinones and their use as inhibitors of neutrophil elastase activity
4-(4-cyanophenyl)-N-(1-methyl-5-oxopyrrolidin-3-yl)-2,5-dioxo-1-[3-(trifluoromethyl)phenyl]-6,7-dihydro-4H-cyclopenta[d]pyrimidine-3-carboxamide	EC50	1 nM	US-9290459: Substituted bicyclic dihydropyrimidinones and their use as inhibitors of neutrophil elastase activity
4-[(4S)-2,5-dioxo-1-[3-(trifluoromethyl)phenyl]-3,4,6,7-tetrahydrocyclopenta[d]pyrimidin-4-yl]-3-ethylsulfonylbenzonitrile	EC50	1 nM	US-9290459: Substituted bicyclic dihydropyrimidinones and their use as inhibitors of neutrophil elastase activity
2-[4-(4-cyano-2-methylsulfonylphenyl)-2,5-dioxo-1-[3-(trifluoromethyl)phenyl]-6,7-dihydro-4H-cyclopenta[d]pyrimidin-3-yl]-N-(2-hydroxyethyl)-N-methylacetamide	EC50	1 nM	US-9290459: Substituted bicyclic dihydropyrimidinones and their use as inhibitors of neutrophil elastase activity
3-methylsulfonyl-4-[3-(2-morpholin-4-yl-2-oxoethyl)-2,5-dioxo-1-[3-(trifluoromethyl)phenyl]-6,7-dihydro-4H-cyclopenta[d]pyrimidin-4-yl]benzonitrile	IC50	1 nM	US-9290459: Substituted bicyclic dihydropyrimidinones and their use as inhibitors of neutrophil elastase activity
4-[3-(3-methoxypropyl)-2,5-dioxo-1-[3-(trifluoromethyl)phenyl]-6,7-dihydro-4H-cyclopenta[d]pyrimidin-4-yl]-3-methylsulfonylbenzonitrile	IC50	1 nM	US-9290459: Substituted bicyclic dihydropyrimidinones and their use as inhibitors of neutrophil elastase activity
4-[(4S)-3-methyl-2,5-dioxo-1-[3-(trifluoromethyl)phenyl]-6,7-dihydro-4H-cyclopenta[d]pyrimidin-4-yl]-3-methylsulfonylbenzonitrile	EC50	1 nM	US-9290459: Substituted bicyclic dihydropyrimidinones and their use as inhibitors of neutrophil elastase activity
4-(4-cyanophenyl)-N-[(2S)-2-hydroxypropyl]-2,5-dioxo-1-[3-(trifluoromethyl)phenyl]-6,7-dihydro-4H-cyclopenta[d]pyrimidine-3-carboxamide	EC50	1 nM	US-9290459: Substituted bicyclic dihydropyrimidinones and their use as inhibitors of neutrophil elastase activity
4-(4-cyanophenyl)-N-[(2R)-2-hydroxypropyl]-2,5-dioxo-1-[3-(trifluoromethyl)phenyl]-6,7-dihydro-4H-cyclopenta[d]pyrimidine-3-carboxamide	IC50	1 nM	US-9290459: Substituted bicyclic dihydropyrimidinones and their use as inhibitors of neutrophil elastase activity
4-(4-cyanophenyl)-N-[(3S,4S)-4-hydroxyoxolan-3-yl]-2,5-dioxo-1-[3-(trifluoromethyl)phenyl]-6,7-dihydro-4H-cyclopenta[d]pyrimidine-3-carboxamide	EC50	1 nM	US-9290459: Substituted bicyclic dihydropyrimidinones and their use as inhibitors of neutrophil elastase activity
(4R)-4-(4-cyanophenyl)-N-(1-imino-1-oxothian-4-yl)-2,5-dioxo-1-[3-(trifluoromethyl)phenyl]-6,7-dihydro-4H-cyclopenta[d]pyrimidine-3-carboxamide	EC50	1 nM	US-9290459: Substituted bicyclic dihydropyrimidinones and their use as inhibitors of neutrophil elastase activity
(4S)-4-(4-cyano-2-methylsulfonylphenyl)-2,5-dioxo-N-propan-2-yl-1-[3-(trifluoromethyl)phenyl]-6,7-dihydro-4H-cyclopenta[d]pyrimidine-3-carboxamide	EC50	1 nM	US-9290459: Substituted bicyclic dihydropyrimidinones and their use as inhibitors of neutrophil elastase activity
4-(4-cyano-2-methoxyphenyl)-N-methyl-2,5-dioxo-1-[3-(trifluoromethyl)phenyl]-6,7-dihydro-4H-cyclopenta[d]pyrimidine-3-carboxamide	IC50	1 nM	US-9290459: Substituted bicyclic dihydropyrimidinones and their use as inhibitors of neutrophil elastase activity
4-(4-cyanophenyl)-1-[3-(difluoromethyl)phenyl]-N-ethyl-2,5-dioxo-6,7-dihydro-4H-cyclopenta[d]pyrimidine-3-carboxamide	EC50	1 nM	US-9290459: Substituted bicyclic dihydropyrimidinones and their use as inhibitors of neutrophil elastase activity
4-(4-cyanophenyl)-1-[3-(difluoromethyl)phenyl]-N-(2-hydroxy-2-methylpropyl)-2,5-dioxo-6,7-dihydro-4H-cyclopenta[d]pyrimidine-3-carboxamide	EC50	1 nM	US-9290459: Substituted bicyclic dihydropyrimidinones and their use as inhibitors of neutrophil elastase activity
N-[[4-(N-cyano-S-propan-2-ylsulfonimidoyl)phenyl]methyl]-6-methyl-1-(2-methylpyrazol-3-yl)-4-oxo-5-[3-(trifluoromethyl)phenyl]pyridine-3-carboxamide	IC50	1 nM	US-9346794: Substituted 4-pyridones and their use as inhibitors of neutrophil elastase activity
N-[[4-(N-cyano-S-ethylsulfonimidoyl)phenyl]methyl]-5-[3-(difluoromethyl)phenyl]-6-methyl-1-(2-methylpyrazol-3-yl)-4-oxopyridine-3-carboxamide	IC50	1 nM	US-9346794: Substituted 4-pyridones and their use as inhibitors of neutrophil elastase activity
5-cyano-2-[3-methyl-2,5-dioxo-1-[3-(trifluoromethyl)phenyl]-6,7-dihydro-4H-cyclopenta[d]pyrimidin-4-yl]-N-(1,3-oxazol-5-ylmethyl)benzamide	IC50	1 nM	US-9458113: Substituted bicyclic dihydropyrimidinones and their use as inhibitors of neutrophil elastase activity
4-[3-methyl-2,5-dioxo-1-[3-(trifluoromethyl)phenyl]-6,7-dihydro-4H-cyclopenta[d]pyrimidin-4-yl]-3-pyridin-4-ylbenzonitrile	IC50	1 nM	US-9458113: Substituted bicyclic dihydropyrimidinones and their use as inhibitors of neutrophil elastase activity
USRE47493, Example 39	IC50	1 nM	US-RE47493
USRE47493, Example 39.2	IC50	1 nM	US-RE47493
USRE47493, Example 39.13	IC50	1 nM	US-RE47493
USRE47493, Example 48	IC50	1 nM	US-RE47493
USRE47493, Example 58.1	IC50	1 nM	US-RE47493
USRE47493, Example 62.5	IC50	1 nM	US-RE47493
3-(2-hydroxyethylsulfonyl)-4-[5-isocyano-4-methyl-2-oxo-3-[3-(trifluoromethyl)phenyl]-1,6-dihydropyrimidin-6-yl]benzonitrile	IC50	1.1 nM	US-9174997: 4-(4-cyano-2-thioaryl)dihydropyrimidinones and use thereof
2-[5-acetyl-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-4H-pyrimidin-4-yl]-5-cyano-N-(3-hydroxycyclopentyl)benzamide	IC50	1.1 nM	US-9290457: Substituted dihydropyrimidinones and their use as inhibitors of neutrophil elastase activity
ethyl 4-[4-cyano-2-[3-methoxypropyl(methyl)carbamoyl]phenyl]-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-4H-pyrimidine-5-carboxylate	IC50	1.1 nM	US-9290457: Substituted dihydropyrimidinones and their use as inhibitors of neutrophil elastase activity
ethyl 4-[4-cyano-2-(2-methylsulfonylethylcarbamoyl)phenyl]-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-4H-pyrimidine-5-carboxylate	IC50	1.1 nM	US-9290457: Substituted dihydropyrimidinones and their use as inhibitors of neutrophil elastase activity

ChEMBL bioactivities

2884 potent at pChembl≥5 of 3137 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	Ki	0.01	nM	CHEMBL538776
10.96	Ki	0.011	nM	CHEMBL163414
10.96	Ki	0.011	nM	CHEMBL348965
10.89	Ki	0.013	nM	CHEMBL114992
10.89	Ki	0.013	nM	CHEMBL164352
10.89	Ki	0.013	nM	CHEMBL142100
10.85	Ki	0.014	nM	CHEMBL435666
10.85	Ki	0.014	nM	CHEMBL543416
10.80	Ki	0.016	nM	CHEMBL140865
10.68	Ki	0.021	nM	CHEMBL142526
10.66	Ki	0.022	nM	CHEMBL12082
10.64	Ki	0.023	nM	CHEMBL115827
10.62	IC50	0.024	nM	CHEMBL5661917
10.60	Ki	0.025	nM	CHEMBL285231
10.60	Ki	0.025	nM	CHEMBL344940
10.60	Ki	0.025	nM	CHEMBL142099
10.57	Ki	0.027	nM	CHEMBL356043
10.52	Ki	0.03	nM	CHEMBL325155
10.52	Ki	0.03	nM	CHEMBL314218
10.52	Ki	0.0302	nM	CHEMBL314218
10.52	Ki	0.03	nM	CHEMBL143819
10.48	Ki	0.033	nM	CHEMBL142960
10.47	Ki	0.034	nM	CHEMBL357694
10.47	IC50	0.034	nM	CHEMBL4204851
10.46	Ki	0.035	nM	CHEMBL41327
10.44	IC50	0.036	nM	CHEMBL2367667
10.37	Ki	0.04266	nM	CHEMBL79428
10.33	IC50	0.047	nM	CHEMBL2367632
10.31	Ki	0.049	nM	CHEMBL11558
10.30	Ki	0.05	nM	CHEMBL143136
10.28	Ki	0.052	nM	CHEMBL343599
10.24	Ki	0.058	nM	CHEMBL142579
10.22	Ki	0.06	nM	CHEMBL142288
10.22	Ki	0.06	nM	CHEMBL403098
10.22	Ki	0.06	nM	CHEMBL339307
10.22	Ki	0.06	nM	CHEMBL91944
10.22	Ki	0.06	nM	CHEMBL320942
10.19	IC50	0.065	nM	CHEMBL3617973
10.18	Ki	0.066	nM	CHEMBL344750
10.17	Ki	0.06761	nM	CHEMBL344066
10.15	Ki	0.07079	nM	CHEMBL432049
10.15	Ki	0.07	nM	CHEMBL430157
10.15	Ki	0.07079	nM	CHEMBL356120
10.15	Ki	0.07	nM	CHEMBL41881
10.11	Ki	0.078	nM	CHEMBL434320
10.10	Ki	0.08	nM	CHEMBL12051
10.10	Ki	0.08	nM	CHEMBL11874
10.10	Ki	0.08	nM	CHEMBL3617973
10.08	Ki	0.083	nM	CHEMBL141329
10.05	Ki	0.09	nM	CHEMBL142555

PubChem BioAssay actives

1803 with measured affinity, of 4805 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(1,1,3-trioxo-4-propan-2-yl-1,2-benzothiazol-2-yl)methyl 2,6-dichlorobenzoate	66820: In vitro inhibition constant of human leukocyte elastase.	ki	<0.0001	uM
(6-methoxy-1,1,3-trioxo-4-propan-2-yl-1,2-benzothiazol-2-yl)methyl 2,6-dichloro-3-(4-methylpiperazin-1-yl)sulfonylbenzoate	66843: Potency of inhibition against human leukocyte elastase (HLE) expressed as an apparent binding constant	ki	<0.0001	uM
(6-methoxy-1,1,3-trioxo-4-propan-2-yl-1,2-benzothiazol-2-yl)methyl 2,6-dichlorobenzoate	66844: Potency of inhibition of human leukocyte elastase is expressed as apparent binding constant	ki	<0.0001	uM
(6-methoxy-1,1,3-trioxo-4-propan-2-yl-1,2-benzothiazol-2-yl)methyl 2,6-dichloro-3-[2-(dimethylamino)ethyl-methylsulfamoyl]benzoate	66843: Potency of inhibition against human leukocyte elastase (HLE) expressed as an apparent binding constant	ki	<0.0001	uM
2-[2,4-dichloro-3-[(6-methoxy-1,1,3-trioxo-4-propan-2-yl-1,2-benzothiazol-2-yl)methoxycarbonyl]phenoxy]acetic acid	66843: Potency of inhibition against human leukocyte elastase (HLE) expressed as an apparent binding constant	ki	<0.0001	uM
2-[(3-benzoyl-6-methyl-2-oxopyran-4-yl)oxymethyl]-6-methoxy-1,1-dioxo-4-propan-2-yl-1,2-benzothiazol-3-one	66844: Potency of inhibition of human leukocyte elastase is expressed as apparent binding constant	ki	<0.0001	uM
2-[(4-chloro-5-oxo-2H-furan-3-yl)oxymethyl]-6-methoxy-1,1-dioxo-4-propan-2-yl-1,2-benzothiazol-3-one	66844: Potency of inhibition of human leukocyte elastase is expressed as apparent binding constant	ki	<0.0001	uM
2-[(3-chloro-6-methyl-2-oxopyran-4-yl)oxymethyl]-6-methoxy-1,1-dioxo-4-propan-2-yl-1,2-benzothiazol-3-one	66844: Potency of inhibition of human leukocyte elastase is expressed as apparent binding constant	ki	<0.0001	uM
6-methoxy-1,1-dioxo-2-[(5-oxo-4-phenyl-2H-furan-3-yl)oxymethyl]-4-propan-2-yl-1,2-benzothiazol-3-one	66844: Potency of inhibition of human leukocyte elastase is expressed as apparent binding constant	ki	<0.0001	uM
2-[(2-benzyl-3-oxocyclopenten-1-yl)oxymethyl]-6-methoxy-1,1-dioxo-4-propan-2-yl-1,2-benzothiazol-3-one	66844: Potency of inhibition of human leukocyte elastase is expressed as apparent binding constant	ki	<0.0001	uM
2-[(4-benzyl-5-oxo-2H-furan-3-yl)oxymethyl]-6-methoxy-1,1-dioxo-4-propan-2-yl-1,2-benzothiazol-3-one	66844: Potency of inhibition of human leukocyte elastase is expressed as apparent binding constant	ki	<0.0001	uM
6-methoxy-1,1-dioxo-2-[(3-oxocyclobuten-1-yl)oxymethyl]-4-propan-2-yl-1,2-benzothiazol-3-one	66844: Potency of inhibition of human leukocyte elastase is expressed as apparent binding constant	ki	<0.0001	uM
sodium [(2S,6S,9S,12S,16R,19E)-6-[(2S)-butan-2-yl]-12-[[(2S)-2-[[2-[(4-hydroxybenzoyl)amino]acetyl]amino]propanoyl]amino]-2-[(4-hydroxyphenyl)methyl]-4,5,8,11,15,18-hexaoxo-9-propyl-23-thia-3,7,10,14,17,24-hexazabicyclo[19.2.1]tetracosa-1(24),19,21-trien-16-yl]methanesulfonate	1819018: Inhibition of human neutrophil elastase	ic50	<0.0001	uM
(4R)-4-[4-cyano-2-(trifluoromethyl)phenyl]-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-4H-pyrimidine-5-carbonitrile	2154505: Inhibition of human neutrophil elastase using MeOSuc-AAPV-MCA as substrate measured at 60 mins interval for up to several hrs by fluorescence assay	ic50	<0.0001	uM
(6-methoxy-1,1,3-trioxo-4-propan-2-yl-1,2-benzothiazol-2-yl)methyl 2,6-dichloro-3-(2-pyrrolidin-1-ylethoxy)benzoate	66843: Potency of inhibition against human leukocyte elastase (HLE) expressed as an apparent binding constant	ki	<0.0001	uM
2-[(4-benzyl-2-methyl-5-oxo-2H-furan-3-yl)oxymethyl]-6-methoxy-1,1-dioxo-4-propan-2-yl-1,2-benzothiazol-3-one	66844: Potency of inhibition of human leukocyte elastase is expressed as apparent binding constant	ki	<0.0001	uM
6-methoxy-2-[(2-methyl-5-oxo-4-phenyl-2H-furan-3-yl)oxymethyl]-1,1-dioxo-4-propan-2-yl-1,2-benzothiazol-3-one	66844: Potency of inhibition of human leukocyte elastase is expressed as apparent binding constant	ki	<0.0001	uM
(1,1,3-trioxo-4-propan-2-yl-1-benzothiophen-2-yl)methyl 2,6-dichloro-3-(4-methylpiperazin-1-yl)sulfonylbenzoate;hydrochloride	66820: In vitro inhibition constant of human leukocyte elastase.	ki	<0.0001	uM
(3aR,6S,6aS)-1-[5-[(cyclopropylamino)methyl]pyrazine-2-carbonyl]-4-methylsulfonyl-6-propan-2-yl-3,3a,6,6a-tetrahydro-2H-pyrrolo[3,2-b]pyrrol-5-one;hydrochloride	66978: The compound was evaluated for its binding affinity towards human neutrophil elastase (HNE)	ki	<0.0001	uM
(1,1,3-trioxo-4-propan-2-yl-1-benzothiophen-2-yl)methyl 2,6-dichloro-3-[2-(dimethylamino)ethyl-methylsulfamoyl]benzoate;hydrochloride	66820: In vitro inhibition constant of human leukocyte elastase.	ki	<0.0001	uM
(1,1,3-trioxo-4-propan-2-yl-1-benzothiophen-2-yl)methyl 2,6-dichloro-3-(2-morpholin-4-ylethoxy)benzoate;hydrochloride	66820: In vitro inhibition constant of human leukocyte elastase.	ki	<0.0001	uM
2-ethoxy-5-ethyl-3,1-benzoxazin-4-one	67499: Inhibition of human leukocyte elastase	ki	<0.0001	uM
benzyl (3aS,6R,6aR)-4-naphthalen-2-ylsulfonyl-5-oxo-6-prop-2-enyl-3,3a,6,6a-tetrahydro-2H-pyrrolo[3,2-b]pyrrole-1-carboxylate	66478: In vitro inhibitory activity against human neutrophil elastase (HNE)	ic50	<0.0001	uM
benzyl (3aS,6R,6aR)-4-methylsulfonyl-5-oxo-6-prop-2-enyl-3,3a,6,6a-tetrahydro-2H-pyrrolo[3,2-b]pyrrole-1-carboxylate	66478: In vitro inhibitory activity against human neutrophil elastase (HNE)	ic50	<0.0001	uM
benzyl N-[(2S)-3-methyl-1-[(2S)-2-[[(2S)-3-methyl-1-[5-[(3-methylphenyl)methyl]-1,3,4-oxadiazol-2-yl]-1-oxobutan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxobutan-2-yl]carbamate	321181: Inhibition of human neutrophil elastase	ki	<0.0001	uM
(1,1,3-trioxo-4-propan-2-yl-1,2-benzothiazol-2-yl)methyl 2,6-dichloro-3-(2-morpholin-4-ylethoxy)benzoate	66843: Potency of inhibition against human leukocyte elastase (HLE) expressed as an apparent binding constant	ki	<0.0001	uM
diethyl (6-methoxy-1,1,3-trioxo-4-propan-2-yl-1,2-benzothiazol-2-yl)methyl phosphate	66822: In vitro inhibitory activity against Human leukocyte elastase	ki	<0.0001	uM
(6-methoxy-1,1,3-trioxo-4-propan-2-yl-1,2-benzothiazol-2-yl)methyl 2,6-dichloro-3-(2-morpholin-4-ylethoxy)benzoate	66678: Binding affinity against Elastase.	ki	<0.0001	uM
(4-butan-2-yl-1,1,3-trioxo-1,2-benzothiazol-2-yl)methyl 2,6-dichlorobenzoate	66820: In vitro inhibition constant of human leukocyte elastase.	ki	0.0001	uM
(4-butan-2-yl-1,1,3-trioxo-1,2-benzothiazol-2-yl)methyl diethyl phosphate	66822: In vitro inhibitory activity against Human leukocyte elastase	ki	0.0001	uM
methyl 2-[(2S)-2-[[(2S)-1-[(2S)-2-[[4-[(4-chlorophenyl)sulfonylcarbamoyl]benzoyl]amino]-3-methylbutanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]-1,3-benzoxazole-5-carboxylate	66809: Inhibition of human neutrophil elastase-catalyzed hydrolysis of the synthetic substrate MeO-Suc-Ala-Ala-Pro-Val-pNa	ki	0.0001	uM
methyl 2-[(2S)-2-[[(2S)-1-[(2S)-2-[[4-[(4-chlorophenyl)sulfonylcarbamoyl]benzoyl]amino]-3-methylbutanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]-1,3-benzoxazole-6-carboxylate	321181: Inhibition of human neutrophil elastase	ki	0.0001	uM
methyl 2-[(2S)-2-[[(2S)-1-[(2S)-2-[[4-[(4-chlorophenyl)sulfonylcarbamoylamino]benzoyl]amino]-3-methylbutanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]-1,3-benzoxazole-5-carboxylate	66809: Inhibition of human neutrophil elastase-catalyzed hydrolysis of the synthetic substrate MeO-Suc-Ala-Ala-Pro-Val-pNa	ki	0.0001	uM
diethyl (1,1,3-trioxo-4-propan-2-yl-1,2-benzothiazol-2-yl)methyl phosphate	66822: In vitro inhibitory activity against Human leukocyte elastase	ki	0.0001	uM
6-methoxy-2-[(2-methyl-3-oxocyclopenten-1-yl)oxymethyl]-1,1-dioxo-4-propan-2-yl-1,2-benzothiazol-3-one	66844: Potency of inhibition of human leukocyte elastase is expressed as apparent binding constant	ki	0.0001	uM
2-[(1-benzyl-5-oxo-2H-pyrrol-3-yl)oxymethyl]-6-methoxy-1,1-dioxo-4-propan-2-yl-1,2-benzothiazol-3-one	66844: Potency of inhibition of human leukocyte elastase is expressed as apparent binding constant	ki	0.0001	uM
6-methoxy-1,1-dioxo-2-[(4-oxo-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-2-yl)oxymethyl]-4-propan-2-yl-1,2-benzothiazol-3-one	66844: Potency of inhibition of human leukocyte elastase is expressed as apparent binding constant	ki	0.0001	uM
6-methoxy-1,1-dioxo-2-[(2-oxochromen-4-yl)oxymethyl]-4-propan-2-yl-1,2-benzothiazol-3-one	66844: Potency of inhibition of human leukocyte elastase is expressed as apparent binding constant	ki	0.0001	uM
6-methoxy-1,1-dioxo-2-[(4-oxopyrido[1,2-a]pyrimidin-2-yl)oxymethyl]-4-propan-2-yl-1,2-benzothiazol-3-one	66844: Potency of inhibition of human leukocyte elastase is expressed as apparent binding constant	ki	0.0001	uM
6-methoxy-2-[(2-methyl-6-oxopyran-4-yl)oxymethyl]-1,1-dioxo-4-propan-2-yl-1,2-benzothiazol-3-one	66844: Potency of inhibition of human leukocyte elastase is expressed as apparent binding constant	ki	0.0001	uM
2-[(3-bromo-4-oxopyrido[1,2-a]pyrimidin-2-yl)oxymethyl]-6-methoxy-1,1-dioxo-4-propan-2-yl-1,2-benzothiazol-3-one	66844: Potency of inhibition of human leukocyte elastase is expressed as apparent binding constant	ki	0.0001	uM
6-methoxy-1,1-dioxo-2-[(5-oxo-2H-furan-3-yl)oxymethyl]-4-propan-2-yl-1,2-benzothiazol-3-one	66844: Potency of inhibition of human leukocyte elastase is expressed as apparent binding constant	ki	0.0001	uM
6-methoxy-1,1-dioxo-2-[(3-oxoinden-1-yl)oxymethyl]-4-propan-2-yl-1,2-benzothiazol-3-one	66844: Potency of inhibition of human leukocyte elastase is expressed as apparent binding constant	ki	0.0001	uM
5-(bromomethyl)-2-ethoxy-3,1-benzoxazin-4-one	67499: Inhibition of human leukocyte elastase	ki	0.0001	uM
2-ethoxy-5-propan-2-yl-3,1-benzoxazin-4-one	67499: Inhibition of human leukocyte elastase	ki	0.0001	uM
3-[2-[2-(thiophene-2-carbonylsulfanyl)propanoylamino]acetyl]-1,3-thiazolidine-4-carboxylic acid	66636: Inhibitory concentration against Human Leukocyte Elastase from human sputum	ic50	0.0001	uM
4-N-(benzenesulfonyl)-1-N-[(2S)-1-[(2S)-2-[[(3S)-5,5-difluoro-2-methyl-4,6-dioxo-6-(2-phenylethylamino)hexan-3-yl]carbamoyl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]benzene-1,4-dicarboxamide	66679: Binding affinity for human leukocyte elastase	ki	0.0001	uM
benzyl N-[(2S)-1-[[(2S)-3-methyl-1-oxo-1-[(2S)-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]carbamoyl]pyrrolidin-1-yl]butan-2-yl]amino]-1-oxo-6-(phenylmethoxycarbonylamino)hexan-2-yl]carbamate	66674: Binding affinity against human leukocyte Elastase	ki	0.0001	uM
6-methoxy-2-[(2-methyl-5-oxo-2H-furan-3-yl)oxymethyl]-1,1-dioxo-4-propan-2-yl-1,2-benzothiazol-3-one	66844: Potency of inhibition of human leukocyte elastase is expressed as apparent binding constant	ki	0.0001	uM
2-ethoxy-5,8-dimethyl-3,1-benzoxazin-4-one	67499: Inhibition of human leukocyte elastase	ki	0.0001	uM

CTD chemical–gene interactions

40 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
1,3-dimethylthiourea	decreases reaction, increases expression	3
N-Formylmethionine Leucyl-Phenylalanine	decreases reaction, increases secretion, affects cotreatment	2
Reactive Oxygen Species	increases abundance, affects reaction, increases expression, increases reaction	2
triphenyl phosphate	affects expression	1
pirinixic acid	affects cotreatment, decreases reaction, increases secretion	1
bisphenol A	affects cotreatment, increases expression	1
potassium persulfate	increases expression	1
lipoteichoic acid	increases secretion, decreases reaction	1
kojic acid	decreases expression	1
sodium arsenite	affects splicing, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
1,2-bis(2-aminophenoxy)ethane N,N,N’,N’-tetraacetic acid acetoxymethyl ester	decreases reaction, increases secretion	1
N-((2-(hydroxyaminocarbonyl)methyl)-4-methylpentanoyl)-3-(2’-naphthyl)alanylalanine, 2-aminoethylamide	decreases reaction, increases expression, increases phosphorylation	1
2-(2-fluorobenzamido)benzoate ethyl ester	decreases reaction, increases secretion	1
Aripiprazole	affects cotreatment, increases expression	1
alpha 1-Antitrypsin	decreases activity	1
Aniline Compounds	increases hydrolysis	1
Arbutin	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	decreases expression	1
Cocaine	affects binding, affects reaction, decreases activity	1
Copper	affects binding, decreases activity	1
Cytochalasin B	affects cotreatment, increases secretion, decreases reaction	1
Deferoxamine	decreases reaction, increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Nitroglycerin	increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Iron	decreases expression	1
Lipids	decreases reaction, increases secretion	1
Lipopolysaccharides	increases secretion, decreases reaction	1

ChEMBL screening assays

801 unique, capped per target: 758 binding, 35 functional, 6 admet, 2 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1004877	Binding	Inhibition of neutrophil elastase in human U937 cells	Inhibition of the activation of multiple serine proteases with a cathepsin C inhibitor requires sustained exposure to prevent pro-enzyme processing. — J Biol Chem
CHEMBL4357082	ADMET	Inhibition of human neutrophil elastase 2 at 100 uM	Discovery of Taniborbactam (VNRX-5133): A Broad-Spectrum Serine- and Metallo-β-lactamase Inhibitor for Carbapenem-Resistant Bacterial Infections. — J Med Chem
CHEMBL5326791	Toxicity	Inhibition of human neutrophil elastase	Structure-guided design of direct-acting antivirals that exploit the gem-dimethyl effect and potently inhibit 3CL proteases of severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) and middle east respiratory syndrome coronavirus (MERS-CoV). — Eur J Med Chem

Cellosaurus cell lines

1 cell lines: 1 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A0JW	SANi007-A	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

182 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00030758	PHASE4	UNKNOWN	Filgrastim or Pegfilgrastim in Preventing Neutropenia in Women Receiving Chemotherapy Following Surgery for Breast Cancer
NCT00125723	PHASE4	COMPLETED	FIRST - Study of Pegfilgrastim Administered in the First and Subsequent Cycles of Myelosuppressive Chemotherapy
NCT00194857	PHASE4	TERMINATED	Treatment of Anemia and Neutropenia in HIV/HCV Coinfected Patients Treated With Pegylated Interferon and Ribavirin
NCT00257790	PHASE4	COMPLETED	The Tobramycin Study
NCT00277160	PHASE4	COMPLETED	A Study of Primary Prophylaxis With Neulasta (Pegfilgrastim) Versus Secondary Prophylaxis After Chemotherapy in Elderly Subjects (>/= 65 Years Old) With Cancer
NCT00686543	PHASE4	COMPLETED	Oral Posaconazole in High Risk Patients With Gastrointestinal Dysfunction (Study P05115)
NCT01086878	PHASE4	COMPLETED	Safety of Cotrimoxazole in HIV- and HAART-exposed Infants
NCT01114165	PHASE4	COMPLETED	Value of the LightCycler® SeptiFast Test MGRADE for the Pathogen Detection in Neutropenic Hematological Patients
NCT01135589	PHASE4	UNKNOWN	Micafungin Prevention Study for Fungal Disease in Child Receiving Allogenic Hematopoietic Stem Cell Transplantation
NCT01571518	PHASE4	UNKNOWN	Prevention of Neutropenia After Using G-CSF With TAC Chemotherapy
NCT02621905	PHASE4	COMPLETED	Steady-State Comparative Bioavailability Study in Prophylaxis Patients of Lozanoc® 50 mg With Sporanox® 100 mg
NCT02967341	PHASE4	UNKNOWN	Blood Draw Validation for Ciprofloxacin Pharmacokinetic Research in Pediatric Cancer Patients
NCT04009941	PHASE4	COMPLETED	Efficacy and Safety of 4.5mg PEG-rhG-CSF Per Cycle in Preventing Neutropenia After Intensive Chemotherapy for Breast Cancer
NCT04904614	PHASE4	COMPLETED	Letermovir Use in Heart Transplant Recipients
NCT05626530	PHASE4	RECRUITING	Letermovir for Secondary Prophylaxis in Solid Organ Transplant Recipients
NCT06145321	PHASE4	ACTIVE_NOT_RECRUITING	Continuous Versus Bolus Administration of G-CSF in Children With Cancer
NCT00001338	PHASE3	COMPLETED	A Prospective, Randomized, Phase III Trial of FLAC (5-Fluorouracil, Leucovorin, Adriamycin, Cytoxan) Chemotherapy With GM-CSF (Granulocyte-Macrophage Colony-Stimulating Factor) Versus PIXY 321 in Advanced Breast Cancer
NCT00001646	PHASE3	COMPLETED	Voriconazole vs. Amphotericin B in the Treatment of Invasive Aspergillosis
NCT00002658	PHASE3	UNKNOWN	Combination Chemotherapy, Biological Therapy, and Bone Marrow Transplantation in Treating Patients With Acute Myeloid Leukemia
NCT00002719	PHASE3	COMPLETED	Combination Chemotherapy With or Without G-CSF in Treating Older Patients With Acute Myeloid Leukemia
NCT00003739	PHASE3	COMPLETED	Antibiotic Therapy With or Without G-CSF in Treating Children With Neutropenia and Fever Caused by Chemotherapy
NCT00020865	PHASE3	UNKNOWN	Levofloxacin Compared With Cefepime in Treating Cancer Patients With Fever and Neutropenia
NCT00035594	PHASE3	COMPLETED	Pegfilgrastim as Support to Advanced Breast Cancer Patients Receiving Chemotherapy
NCT00044486	PHASE3	COMPLETED	Prophylaxis Trial of Posaconazole Versus Standard Azole Therapy for Neutropenic Patients (Study P01899)
NCT00107081	PHASE3	TERMINATED	Low-risk Fever and Neutropenia in Children With Cancer: Safety and Efficacy of Oral Antibiotics in an Outpatient Setting
NCT00445497	PHASE3	UNKNOWN	Early Hospital Discharge or Standard Inpatient Care in Cancer Patients Receiving Antibiotics for Febrile Neutropenia
NCT00529282	PHASE3	TERMINATED	A Study of Ceftobiprole in Patients With Fever and Neutropenia.
NCT00627393	PHASE3	COMPLETED	Safety and Effectiveness of Granulocyte Transfusions in Resolving Infection in People With Neutropenia (The RING Study)
NCT00770172	PHASE3	COMPLETED	G-CSF in Preventing Neutropenia in Patients With Solid Tumors Who Are Receiving Chemotherapy
NCT00784368	PHASE3	COMPLETED	A Pharmacokinetic Study of JK1211(Itraconazole [Itrizole]) Oral Solution in Participants With Deep Mycosis and Those With Febrile Neutropenia Suspected of Fungal Infection
NCT00806351	PHASE3	TERMINATED	An Evaluation Of The Effectiveness And Safety Of Anidulafungin Compared To Caspofungin For The Treatment Of Serious Fungal Infection Due To Candida In Patients With A Dysfunctional Immune System
NCT00911170	PHASE3	COMPLETED	PAVES: Pegfilgrastim Anti-vascular Endothelial Growth Factor (VEGF) Evaluation Study
NCT01307579	PHASE3	COMPLETED	Caspofungin Versus Fluconazole in Preventing Invasive Fungal Infections (IFI) in Patients Undergoing Chemotherapy for Acute Myeloid Leukemia
NCT01371656	PHASE3	COMPLETED	Levofloxacin in Preventing Infection in Young Patients With Acute Leukemia Receiving Chemotherapy or Undergoing Stem Cell Transplantation
NCT01560195	PHASE3	UNKNOWN	A Study of Pegylated rhG-CSF as Support to Advanced Non-Small-Cell Lung Cancer (NSCLC) Patients Receiving Chemotherapy Receiving Chemotherapy
NCT01611051	PHASE3	COMPLETED	A Study Comparing Pegylated rhG-CSF and rhG-CSF as Support to Breast Cancer Patients Receiving Chemotherapy
NCT02238873	PHASE3	UNKNOWN	Pegfilgrastim on Day +3 Compared to Day +1 After Salvage Chemotherapy for Patients With Refractory or Relapsed Aggressive Lymphoma
NCT02414581	PHASE3	COMPLETED	Mouthwash With Chlorhexidine 0.12%/Ethyl Alcohol 7% Compared to Ethyl Alcohol 7%
NCT02643420	PHASE3	COMPLETED	SPI-2012 vs Pegfilgrastim in the Management of Neutropenia in Participants With Breast Cancer With Docetaxel and Cyclophosphamide (ADVANCE)
NCT02872103	PHASE3	COMPLETED	Placebo-controlled Trial of F-627 in Women With Breast Cancer Receiving Myelotoxic Chemotherapy