Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTPLTSQ)

• DTT Name: Neutrophil elastase (NE)
• Synonyms: PMN elastase; Medullasin; Human leukocyte elastase; HLE; Elastase-2; ELA2; Bone marrow serine protease
• Gene Name: ELANE
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Peptidase
• UniProt ID: ELNE_HUMAN
• TTD ID: T40332
• EC Number: EC 3.4.21.37
• Sequence:
  MTLGRRLACLFLACVLPALLLGGTALASEIVGGRRARPHAWPFMVSLQLRGGHFCGATLI
  APNFVMSAAHCVANVNVRAVRVVLGAHNLSRREPTRQVFAVQRIFENGYDPVNLLNDIVI
  LQLNGSATINANVQVAQLPAQGRRLGNGVQCLAMGWGLLGRNRGIASVLQELNVTVVTSL
  CRRSNVCTLVRGRQAGVCFGDSGSPLVCNGLIHGIASFVRGGCASGLYPDAFAPVAQFVN
  WIDSIIQRSEDNPCPHPRDPDPASRTH
• Function: Inhibits C5a-dependent neutrophil enzyme release and chemotaxis. Modifies the functions of natural killer cells, monocytes and granulocytes.
• KEGG Pathway:
  Transcriptional misregulation in cancer (hsa05202)
  Systemic lupus erythematosus (hsa05322)
• Reactome Pathway:
  Degradation of the extracellular matrix (R-HSA-1474228)
  Activation of Matrix Metalloproteinases (R-HSA-1592389)
  Collagen degradation (R-HSA-1442490)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sivelestat sodium hydrate	DMOSJD0	Acute lung injury	NB32.3	Phase 4	[1]

10 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Epigallocatechin gallate	DMCGWBJ	Hepatic fibrosis	DB93.0	Phase 3	[2]
Sivelestat	DM6BZCV	Crohn disease	DD70	Phase 3	[3]
AZD9668	DMB87M3	Bronchiectasis	CA24	Phase 2	[4]
BAY 85-8501	DMCPUKG	Bronchiectasis	CA24	Phase 2	[5]
DX-890	DMBFZET	Acute lung injury	NB32.3	Phase 2	[1]
L-694,458	DMA0DSJ	Cystic fibrosis	CA25	Phase 2	[6]
Tiprelestat	DM1SB94	Myocardial infarction	BA41-BA43	Phase 2	[7]
AZD-9819	DMWYHXG	Chronic obstructive pulmonary disease	CA22	Phase 1	[8]
BI 1323495	DMAUKTS	Chronic obstructive pulmonary disease	CA22	Phase 1	[9]
POL-6014	DM9B68S	Cystic fibrosis	CA25	Phase 1	[10]

33 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
2-pyrazinone derivative 1	DMWXUS4	N. A.	N. A.	Patented	[11]
2-pyrazinone derivative 2	DMLEH4U	N. A.	N. A.	Patented	[11]
2-pyrazinone derivative 3	DME5WLD	N. A.	N. A.	Patented	[11]
2-pyrazinone derivative 4	DMJRHS4	N. A.	N. A.	Patented	[11]
2-pyrazinone derivative 5	DMBIRMA	N. A.	N. A.	Patented	[11]
2-pyrazinone derivative 6	DMHIEBN	N. A.	N. A.	Patented	[11]
2-pyrazinone derivative 7	DMTG6X9	N. A.	N. A.	Patented	[11]
4-pyridone derivative 1	DMMBUGK	N. A.	N. A.	Patented	[11]
4-pyridone derivative 2	DMS1O0G	N. A.	N. A.	Patented	[11]
Dihydropyrimidinone derivative 1	DMA25XH	N. A.	N. A.	Patented	[11]
Dihydropyrimidinone derivative 2	DM5Y13R	N. A.	N. A.	Patented	[11]
Hypersulfated disaccharide compound 1	DMMFI5G	N. A.	N. A.	Patented	[11]
Peptide analog 55	DMVLP8H	N. A.	N. A.	Patented	[11]
Peptide analog 56	DMBCFJU	N. A.	N. A.	Patented	[11]
Peptide analog 57	DM6IQWE	N. A.	N. A.	Patented	[11]
Peptide analog 58	DM7X62M	N. A.	N. A.	Patented	[11]
Peptide analog 59	DMZAMNX	N. A.	N. A.	Patented	[11]
Peptide analog 60	DMMSTNA	N. A.	N. A.	Patented	[11]
Peptide analog 61	DM45JMT	N. A.	N. A.	Patented	[11]
Peptide analog 62	DM28NK0	N. A.	N. A.	Patented	[11]
Peptide analog 63	DMGC7NW	N. A.	N. A.	Patented	[11]
Peptide analog 64	DM1G2J5	N. A.	N. A.	Patented	[11]
Peptide analog 65	DMAJLM1	N. A.	N. A.	Patented	[11]
Peptide analog 66	DMW502M	N. A.	N. A.	Patented	[11]
Peptide analog 67	DMJ8QTX	N. A.	N. A.	Patented	[11]
Peptide analog 68	DMFG2KT	N. A.	N. A.	Patented	[11]
Peptide analog 69	DM2OXW3	N. A.	N. A.	Patented	[11]
Peptide analog 70	DMN43Q5	N. A.	N. A.	Patented	[11]
Pyrimidine derivative 34	DM4192V	N. A.	N. A.	Patented	[11]
Pyrimidinone derivative 4	DMDQNKW	N. A.	N. A.	Patented	[11]
Tetra-hydro-pyrrolopyrimidinedione derivative 1	DMM06K5	N. A.	N. A.	Patented	[11]
Tetra-hydro-triazolopyrimidine derivative 2	DMI6VG9	N. A.	N. A.	Patented	[12]
Uracil derivative 1	DM5SX8T	N. A.	N. A.	Patented	[11]

14 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
MR-889	DMYQZBT	Phlegmy cough	SA80-SA8Z	Discontinued in Phase 3	[6]
CE-1037	DM746L8	Chronic obstructive pulmonary disease	CA22	Discontinued in Phase 2	[6]
Dermolastin	DM6WSU2	Atopic dermatitis	EA80	Discontinued in Phase 2	[13]
FK-706	DM524J3	Pulmonary emphysema	CA21.Z	Discontinued in Phase 2	[6]
ZD-8321	DMBSXPJ	Acute lung injury	NB32.3	Discontinued in Phase 2	[6]
AE-3763	DMRSEZD	Chronic obstructive pulmonary disease	CA22	Discontinued in Phase 1	[6]
AZD-6553	DMQZCET	Chronic obstructive pulmonary disease	CA22	Discontinued in Phase 1	[14]
FR167653	DM69OR8	Chronic obstructive pulmonary disease	CA22	Discontinued in Phase 1	[6]
GW-311616	DM62T1C	N. A.	N. A.	Discontinued in Phase 1	[6]
ZD-0892	DM82V1D	Chronic obstructive pulmonary disease	CA22	Discontinued in Phase 1	[6]
FR-901277	DM6PFVD	N. A.	N. A.	Terminated	[15]
FR-901451	DM2FNPO	N. A.	N. A.	Terminated	[15]
Mdl 101,146	DMRSOBG	Inflammation	1A00-CA43.1	Terminated	[16]
SR-26831	DM1GKTS	Rheumatoid arthritis	FA20	Terminated	[17]

47 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(1H-pyrazol-1-yl)(o-tolyl)methanone	DMACN68	Discovery agent	N.A.	Investigative	[18]
(3,4-dichlorophenyl)(1H-pyrazol-1-yl)methanone	DMNVDLI	Discovery agent	N.A.	Investigative	[18]
(3-nitro-1H-pyrazol-1-yl)(p-tolyl)methanone	DMT9FZD	Discovery agent	N.A.	Investigative	[18]
(3-nitro-1H-pyrazol-1-yl)(phenyl)methanone	DMD4Z6H	Discovery agent	N.A.	Investigative	[18]
(4-bromo-1H-pyrazol-1-yl)(m-tolyl)methanone	DMS9125	Discovery agent	N.A.	Investigative	[18]
(4-bromo-1H-pyrazol-1-yl)(o-tolyl)methanone	DM5QDK9	Discovery agent	N.A.	Investigative	[18]
(4-bromo-1H-pyrazol-1-yl)(p-tolyl)methanone	DM31OSD	Discovery agent	N.A.	Investigative	[18]
(4-chloro-1H-pyrazol-1-yl)(o-tolyl)methanone	DM4MAZ1	Discovery agent	N.A.	Investigative	[18]
(4-nitro-1H-pyrazol-1-yl)(o-tolyl)methanone	DMBPL3J	Discovery agent	N.A.	Investigative	[18]
(4-nitro-1H-pyrazol-1-yl)(phenyl)methanone	DMIDUO9	Discovery agent	N.A.	Investigative	[18]
1-(3,3-Dimethyl-2-oxo-butyl)-1H-indole-2,3-dione	DMNZYWR	Discovery agent	N.A.	Investigative	[19]
1-benzoyl-N-phenyl-1H-pyrazole-3-carboxamide	DMG5MNZ	Discovery agent	N.A.	Investigative	[18]
1-benzyl-3,3-diethylazetidine-2,4-dione	DMPTMKU	Discovery agent	N.A.	Investigative	[20]
1-benzyl-3,3-dimethylazetidine-2,4-dione	DMW59XA	Discovery agent	N.A.	Investigative	[20]
2-methylbut-3-yn-2-yl 4-methoxybenzoate	DMKB2P8	Discovery agent	N.A.	Investigative	[18]
3,3-Diethyl-1-(pyridin-3-yl)azetidine-2,4-dione	DMWFD5C	Discovery agent	N.A.	Investigative	[20]
3,3-Diethyl-1-o-tolylazetidine-2,4-dione	DMY8S94	Discovery agent	N.A.	Investigative	[20]
3,3-diethyl-1-phenylazetidine-2,4-dione	DMCFJIP	Discovery agent	N.A.	Investigative	[20]
3,4-dichloroisocoumarin	DMOZCDK	Discovery agent	N.A.	Investigative	[21]
3-Benzyl-3-ethyl-1-phenylazetidine-2,4-dione	DMDAO28	Discovery agent	N.A.	Investigative	[20]
3-Benzyl-3-methyl-1-phenylazetidine-2,4-dione	DMHINWF	Discovery agent	N.A.	Investigative	[20]
3-butyl-3-ethyl-1-phenylazetidine-2,4-dione	DMOGZUK	Discovery agent	N.A.	Investigative	[20]
3-Decanoyl-4-hydroxy-6-nonyl-pyran-2-one	DMLQJ64	Discovery agent	N.A.	Investigative	[22]
3-Ethyl-3-isobutyl-1-phenylazetidine-2,4-dione	DMB8Q7T	Discovery agent	N.A.	Investigative	[20]
4-Hydroxy-3-nonanoyl-6-octyl-pyran-2-one	DMDEMV8	Discovery agent	N.A.	Investigative	[22]
4-methoxy-N'-(2-phenylacetyl)benzohydrazide	DMF079L	Discovery agent	N.A.	Investigative	[18]
6-Heptyl-4-hydroxy-3-octanoyl-pyran-2-one	DMF3W15	Discovery agent	N.A.	Investigative	[22]
Ac-Ala-Pro-Val-(2-benzoxazole)	DMJ3C20	Discovery agent	N.A.	Investigative	[23]
ADC-7828	DM19KY6	Chronic obstructive pulmonary disease	CA22	Investigative	[10]
AX-9657	DMKCT0M	Pulmonary disease	1B10-1F85	Investigative	[10]
Bornyl (3,4,5-trihydroxy)-cinnamate	DMR70ZO	Discovery agent	N.A.	Investigative	[24]
Cbz-Val-Pro-Val-(2-benzoxazole)	DM6TYRA	Discovery agent	N.A.	Investigative	[23]
DD7	DMV0JQG	Acute respiratory distress syndrome	CB00	Investigative	[25]
E-6-O-p-methoxycinnamoyl scandoside methyl ester	DM7ROJI	Discovery agent	N.A.	Investigative	[2]
ED1	DM5QS17	Acute respiratory distress syndrome	CB00	Investigative	[25]
ED45	DMX32JY	Acute respiratory distress syndrome	CB00	Investigative	[25]
Fucose	DMAHMSV	N. A.	N. A.	Investigative	[16]
ICI 200,355	DMLPZ3N	Discovery agent	N.A.	Investigative	[26]
ICI 200,880	DM0PQ37	Discovery agent	N.A.	Investigative	[6]
L-658,758	DMY0IQ6	Discovery agent	N.A.	Investigative	[27]
N,N-bis(cyanomethyl)-3,4-dimethoxybenzamide	DMBQ0TY	Discovery agent	N.A.	Investigative	[18]
PMID22595175C4g	DM9SLUK	Discovery agent	N.A.	Investigative	[28]
PMID24556381C10f	DMK6GAU	Discovery agent	N.A.	Investigative	[29]
PMID24556381C10l	DMOH45T	Discovery agent	N.A.	Investigative	[29]
TEI-8362	DMBNYJW	Discovery agent	N.A.	Investigative	[6]
WIN-63395	DMNM50K	Discovery agent	N.A.	Investigative	[30]
ZK-814048	DMCBV5F	Discovery agent	N.A.	Investigative	[31]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Chronic obstructive pulmonary disease	CA23	Lung tissue	9.42E-01	0.02	0.07
Chronic obstructive pulmonary disease	CA23	Small airway epithelium	1.43E-02	0.05	0.2
Rheumatoid arthritis	FA20	Synovial tissue	8.29E-02	0.18	1.1
Atopic dermatitis	EA90	Skin	1.09E-06	-0.87	-1.2
Asthma	CA23	Nasal and bronchial airway	1.68E-01	0.03	0.14
Multiple myeloma	2C82	Bone marrow	2.35E-01	-0.55	-0.82
Preterm birth	KA21.4Z	Myometrium	7.82E-01	0.09	0.3
Sepsis with septic shock	1G41	Whole blood	2.67E-93	1.41	3.01

References

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