Target Information
Target General Infomation | |||||
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Target ID |
T40332
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Former ID |
TTDS00448
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Target Name |
Leukocyte elastase
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Gene Name |
ELANE
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Synonyms |
Bone marrow serine protease; Medullasin; Neutrophil elastase; PMN elastase; ELANE
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Target Type |
Clinical Trial
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Disease | Acute lung injury; Acute respiratory distress syndrome; Cystic fibrosis [ICD9: 277.0, 518.5, 518.82, 709.2; ICD10: E84, J80, L90.5] | ||||
Acute lung injury; Acute respiratory distress syndrome [ICD9: 518.5, 518.82; ICD10: J80] | |||||
Atopic dermatitis [ICD9: 691.8, 692.9; ICD10: L00-L99] | |||||
Asthma; Chronic obstructive pulmonary disease [ICD9: 490-492, 493, 494-496; ICD10: J40-J44, J47, J45] | |||||
Acute lung injury [ICD9: 518; ICD10: J80] | |||||
Bronchiectasis [ICD9: 494, 748.61; ICD10: J47, Q33.4] | |||||
Chronic obstructive pulmonary disease [ICD9: 490-492, 494-496; ICD10: J40-J44, J47] | |||||
Cystic fibrosis [ICD9: 277; ICD10: E84] | |||||
Inflammatory disease [ICD9: 140-229, 147, 173, 573.3, 710-719; ICD10: C11, C44, K75.9, M00-M25] | |||||
Mucolytic [ICD10: J00-J99] | |||||
Myocardial infarction [ICD9: 410; ICD10: I21, I22] | |||||
Pulmonary disease [ICD9: 460-519; ICD10: J00-J99] | |||||
Pulmonary emphysema [ICD10: J43] | |||||
Rheumatoid arthritis [ICD9: 710-719, 714; ICD10: M05-M06] | |||||
Septic shock; Myocardial ischaemia-reperfusion injury; Acute respiratory distress syndrome [ICD9: 492, 518.5, 518.82, 785.52; ICD10: A41.9, J43, J80] | |||||
Function |
Modifies the functions of natural killer cells, monocytes and granulocytes. Inhibits C5a-dependent neutrophil enzyme release and chemotaxis.
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BioChemical Class |
Peptidase
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Target Validation |
T40332
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UniProt ID | |||||
EC Number |
EC 3.4.21.37
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Sequence |
MTLGRRLACLFLACVLPALLLGGTALASEIVGGRRARPHAWPFMVSLQLRGGHFCGATLI
APNFVMSAAHCVANVNVRAVRVVLGAHNLSRREPTRQVFAVQRIFENGYDPVNLLNDIVI LQLNGSATINANVQVAQLPAQGRRLGNGVQCLAMGWGLLGRNRGIASVLQELNVTVVTSL CRRSNVCTLVRGRQAGVCFGDSGSPLVCNGLIHGIASFVRGGCASGLYPDAFAPVAQFVN WIDSIIQRSEDNPCPHPRDPDPASRTH |
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Drugs and Mode of Action | |||||
Drug(s) | Sivelestat | Drug Info | Phase 4 | Discovery agent | [521724], [541582] |
Sivelestat sodium hydrate | Drug Info | Phase 4 | Acute lung injury; Acute respiratory distress syndrome | [536361] | |
BAY 85-8501 | Drug Info | Phase 2 | Bronchiectasis | [549458] | |
DX-890 | Drug Info | Phase 2 | Acute lung injury; Acute respiratory distress syndrome; Cystic fibrosis | [522003] | |
L-694,458 | Drug Info | Phase 2 | Cystic fibrosis | [551850] | |
Tiprelestat | Drug Info | Phase 2 | Myocardial infarction | [548073] | |
AZD-9819 | Drug Info | Phase 1 | Chronic obstructive pulmonary disease | [523120] | |
MR-889 | Drug Info | Discontinued in Phase 3 | Mucolytic | [545562] | |
AZD9668 | Drug Info | Discontinued in Phase 2 | Chronic obstructive pulmonary disease | [541611], [548573] | |
CE-1037 | Drug Info | Discontinued in Phase 2 | Chronic obstructive pulmonary disease | [545583] | |
Dermolastin | Drug Info | Discontinued in Phase 2 | Atopic dermatitis | [547642] | |
FK-706 | Drug Info | Discontinued in Phase 2 | Pulmonary emphysema | [546595] | |
ZD-8321 | Drug Info | Discontinued in Phase 2 | Acute lung injury | [546286] | |
AE-3763 | Drug Info | Discontinued in Phase 1 | Chronic obstructive pulmonary disease | [547367] | |
AZD-6553 | Drug Info | Discontinued in Phase 1 | Chronic obstructive pulmonary disease | [549132] | |
GW-311616 | Drug Info | Discontinued in Phase 1 | Discovery agent | [546572] | |
ONO-6818 | Drug Info | Discontinued in Phase 1 | Chronic obstructive pulmonary disease | [547077] | |
ZD-0892 | Drug Info | Discontinued in Phase 1 | Chronic obstructive pulmonary disease | [546659] | |
FR-901277 | Drug Info | Terminated | Discovery agent | [546457] | |
FR-901451 | Drug Info | Terminated | Discovery agent | [546253] | |
Mdl 101,146 | Drug Info | Terminated | Inflammatory disease | [546375] | |
SR-26831 | Drug Info | Terminated | Rheumatoid arthritis | [544831] | |
Inhibitor | (1H-pyrazol-1-yl)(o-tolyl)methanone | Drug Info | [529037] | ||
(3,4-dichlorophenyl)(1H-pyrazol-1-yl)methanone | Drug Info | [529037] | |||
(3-nitro-1H-pyrazol-1-yl)(p-tolyl)methanone | Drug Info | [529037] | |||
(3-nitro-1H-pyrazol-1-yl)(phenyl)methanone | Drug Info | [529037] | |||
(4-bromo-1H-pyrazol-1-yl)(m-tolyl)methanone | Drug Info | [529037] | |||
(4-bromo-1H-pyrazol-1-yl)(o-tolyl)methanone | Drug Info | [529037] | |||
(4-bromo-1H-pyrazol-1-yl)(p-tolyl)methanone | Drug Info | [529037] | |||
(4-chloro-1H-pyrazol-1-yl)(o-tolyl)methanone | Drug Info | [529037] | |||
(4-nitro-1H-pyrazol-1-yl)(o-tolyl)methanone | Drug Info | [529037] | |||
(4-nitro-1H-pyrazol-1-yl)(phenyl)methanone | Drug Info | [529037] | |||
1-(3,3-Dimethyl-2-oxo-butyl)-1H-indole-2,3-dione | Drug Info | [525916] | |||
1-benzoyl-N-phenyl-1H-pyrazole-3-carboxamide | Drug Info | [529037] | |||
1-benzyl-3,3-diethylazetidine-2,4-dione | Drug Info | [530511] | |||
1-benzyl-3,3-dimethylazetidine-2,4-dione | Drug Info | [530511] | |||
2-methylbut-3-yn-2-yl 4-methoxybenzoate | Drug Info | [529037] | |||
3,3-Diethyl-1-(pyridin-3-yl)azetidine-2,4-dione | Drug Info | [530511] | |||
3,3-Diethyl-1-o-tolylazetidine-2,4-dione | Drug Info | [530511] | |||
3,3-diethyl-1-phenylazetidine-2,4-dione | Drug Info | [530511] | |||
3,4-dichloroisocoumarin | Drug Info | [528555] | |||
3-Benzyl-3-ethyl-1-phenylazetidine-2,4-dione | Drug Info | [530511] | |||
3-Benzyl-3-methyl-1-phenylazetidine-2,4-dione | Drug Info | [530511] | |||
3-butyl-3-ethyl-1-phenylazetidine-2,4-dione | Drug Info | [530511] | |||
3-Decanoyl-4-hydroxy-6-nonyl-pyran-2-one | Drug Info | [533472] | |||
3-Ethyl-3-isobutyl-1-phenylazetidine-2,4-dione | Drug Info | [530511] | |||
4-Hydroxy-3-nonanoyl-6-octyl-pyran-2-one | Drug Info | [533472] | |||
4-methoxy-N'-(2-phenylacetyl)benzohydrazide | Drug Info | [529037] | |||
6-Heptyl-4-hydroxy-3-octanoyl-pyran-2-one | Drug Info | [533472] | |||
Ac-Ala-Pro-Val-(2-benzoxazole) | Drug Info | [529193] | |||
ADC-7828 | Drug Info | [543602] | |||
AE-3763 | Drug Info | [535494] | |||
AX-9657 | Drug Info | [543602] | |||
AZD-6553 | Drug Info | [549133] | |||
AZD-9819 | Drug Info | [533294] | |||
AZD9668 | Drug Info | [550288] | |||
Bornyl (3,4,5-trihydroxy)-cinnamate | Drug Info | [529218] | |||
Cbz-Val-Pro-Val-(2-benzoxazole) | Drug Info | [529193] | |||
CE-1037 | Drug Info | [535494] | |||
compound 10f | Drug Info | [532680] | |||
compound 10l | Drug Info | [532680] | |||
compound 4g | Drug Info | [531910] | |||
Dermolastin | Drug Info | [536190], [536840], [537435], [551533] | |||
DX-890 | Drug Info | [536500] | |||
E-6-O-p-methoxycinnamoyl scandoside methyl ester | Drug Info | [530569] | |||
EPIGALOCATECHIN GALLATE | Drug Info | [530569] | |||
FK-706 | Drug Info | [535494] | |||
FR-901277 | Drug Info | [528807] | |||
FR-901451 | Drug Info | [528807] | |||
Fucose | Drug Info | [551393] | |||
GW-311616 | Drug Info | [535494] | |||
ICI 200,355 | Drug Info | [534889], [534999], [537654], [537940], [538031] | |||
ICI 200,880 | Drug Info | [535494], [537900] | |||
L-658,758 | Drug Info | [538111] | |||
L-694,458 | Drug Info | [535494] | |||
Mdl 101,146 | Drug Info | [551393] | |||
MR-889 | Drug Info | [535494] | |||
N,N-bis(cyanomethyl)-3,4-dimethoxybenzamide | Drug Info | [529037] | |||
ONO-6818 | Drug Info | [535494] | |||
POL-6014 | Drug Info | [543602] | |||
Sivelestat | Drug Info | [537032] | |||
Sivelestat sodium hydrate | Drug Info | [536500] | |||
TEI-8362 | Drug Info | [535494] | |||
WIN-63395 | Drug Info | [551308] | |||
ZD-0892 | Drug Info | [535494] | |||
ZD-8321 | Drug Info | [535494] | |||
ZK-814048 | Drug Info | [528872] | |||
Modulator | BAY 85-8501 | Drug Info | [533269] | ||
SR-26831 | Drug Info | [528753] | |||
Tiprelestat | Drug Info | ||||
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM) | |||||
TEP | EXP Info | ||||
Pathways | |||||
KEGG Pathway | Transcriptional misregulation in cancer | ||||
Systemic lupus erythematosus | |||||
Pathway Interaction Database | Urokinase-type plasminogen activator (uPA) and uPAR-mediated signaling | ||||
C-MYB transcription factor network | |||||
Reactome | Collagen degradation | ||||
Degradation of the extracellular matrix | |||||
Activation of Matrix Metalloproteinases | |||||
WikiPathways | Cytodifferentiation (Part 3 of 3) | ||||
Human Complement System | |||||
Degradation of collagen | |||||
References | |||||
Ref 521724 | ClinicalTrials.gov (NCT00219375) Study of Sivelestat Sodium Hydrate in Acute Lung Injury (ALI) Associated With Systemic Inflammatory Response Syndrome (SIRS) in Japan. U.S. National Institutes of Health. | ||||
Ref 522003 | ClinicalTrials.gov (NCT00455767) Safety and Efficacy Study of Depelestat in Acute Respiratory Distress Syndrome (ARDS) Patients. U.S. National Institutes of Health. | ||||
Ref 523120 | ClinicalTrials.gov (NCT01166698) Single Centre, Double-blind, Single and Multiple Ascending Inhaled Doses of AZD9819 in Healthy Subjects. U.S. National Institutes of Health. | ||||
Ref 536361 | Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77. Epub 2007 Feb 20. | ||||
Ref 541582 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6441). | ||||
Ref 541611 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6476). | ||||
Ref 544831 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001260) | ||||
Ref 545562 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003709) | ||||
Ref 545583 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003784) | ||||
Ref 546253 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007127) | ||||
Ref 546286 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007250) | ||||
Ref 546375 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007771) | ||||
Ref 546457 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008229) | ||||
Ref 546572 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008997) | ||||
Ref 546595 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800009108) | ||||
Ref 546659 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800009537) | ||||
Ref 547077 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800012873) | ||||
Ref 547367 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800015539) | ||||
Ref 547642 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800018071) | ||||
Ref 548073 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800021706) | ||||
Ref 548573 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800026715) | ||||
Ref 549132 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800032703) | ||||
Ref 525916 | Bioorg Med Chem Lett. 2000 Nov 20;10(22):2501-4.Parallel synthesis of isatin-based serine protease inhibitors. | ||||
Ref 528555 | Antimicrob Agents Chemother. 2007 Feb;51(2):543-50. Epub 2006 Dec 4.Cathepsin A is the major hydrolase catalyzing the intracellular hydrolysis of the antiretroviral nucleotide phosphonoamidate prodrugs GS-7340 and GS-9131. | ||||
Ref 528753 | Biochemical and pharmacological activities of SR 26831, a potent and selective elastase inhibitor. J Pharmacol Exp Ther. 1992 Feb;260(2):809-16. | ||||
Ref 528807 | Bioorg Med Chem. 2007 Jul 1;15(13):4618-28. Epub 2007 Apr 3.Resisting degradation by human elastase: commonality of design features shared by 'canonical' plant and bacterial macrocyclic protease inhibitor scaffolds. | ||||
Ref 528872 | J Med Chem. 2007 Jun 28;50(13):2967-80. Epub 2007 May 31.Thiophene-anthranilamides as highly potent and orally available factor Xa inhibitors. | ||||
Ref 529037 | J Med Chem. 2007 Oct 4;50(20):4928-38. Epub 2007 Sep 12.N-benzoylpyrazoles are novel small-molecule inhibitors of human neutrophil elastase. | ||||
Ref 529193 | Bioorg Med Chem. 2008 Feb 15;16(4):1562-95. Epub 2007 Nov 6.Inhibitors of proteases and amide hydrolases that employ an alpha-ketoheterocycle as a key enabling functionality. | ||||
Ref 529218 | Bioorg Med Chem. 2008 Mar 1;16(5):2385-90. Epub 2007 Nov 29.Bornyl (3,4,5-trihydroxy)-cinnamate--an optimized human neutrophil elastase inhibitor designed by free energy calculations. | ||||
Ref 530511 | J Med Chem. 2010 Jan 14;53(1):241-53.4-Oxo-beta-lactams (azetidine-2,4-diones) are potent and selective inhibitors of human leukocyte elastase. | ||||
Ref 530569 | Bioorg Med Chem Lett. 2010 Jan 15;20(2):513-5. Epub 2009 Nov 26.Evaluation of human neutrophil elastase inhibitory effect of iridoid glycosides from Hedyotis diffusa. | ||||
Ref 531910 | N-Acyl and N-sulfonyloxazolidine-2,4-diones are pseudo-irreversible inhibitors of serine proteases. Bioorg Med Chem Lett. 2012 Jun 15;22(12):3993-7. | ||||
Ref 532680 | Synthesis and evaluation of 2-(1H-indol-3-yl)-4-phenylquinolines as inhibitors of cholesterol esterase. Bioorg Med Chem Lett. 2014 Mar 15;24(6):1545-9. | ||||
Ref 533269 | Freezing the Bioactive Conformation to Boost Potency: The Identification of BAY??5-8501, a Selective and Potent Inhibitor of Human Neutrophil Elastase for Pulmonary Diseases. ChemMedChem. 2015 Jul;10(7):1163-73. | ||||
Ref 533294 | Lipid Peroxide-Mediated Oxidative Rearrangement of the Pyrazinone Carboxamide Core of Neutrophil Elastase Inhibitor AZD9819 in Blood Plasma Samples. Drug Metab Dispos. 2015 Oct;43(10):1441-9. | ||||
Ref 533472 | J Med Chem. 1987 Jun;30(6):1017-23.Inhibition of human sputum elastase by substituted 2-pyrones. | ||||
Ref 534889 | LTB(4)-induced nasal gland serous cell secretion mediated by neutrophil elastase. Am J Respir Crit Care Med. 1999 Aug;160(2):411-4. | ||||
Ref 534999 | Role of neutrophil elastase in hypersecretion in asthma. Eur Respir J. 1999 Jan;13(1):190-6. | ||||
Ref 535494 | Neutrophil elastase inhibitors as treatment for COPD. Expert Opin Investig Drugs. 2002 Jul;11(7):965-80. | ||||
Ref 536500 | Emerging therapies for treatment of acute lung injury and acute respiratory distress syndrome. Expert Opin Emerg Drugs. 2007 Sep;12(3):461-77. | ||||
Ref 536840 | Bioreactor strategies for improving production yield and functionality of a recombinant human protein in transgenic tobacco cell cultures. Biotechnol Bioeng. 2009 Feb 1;102(2):508-20. | ||||
Ref 537032 | Neutrophil elastase inhibitor (sivelestat) reduces the levels of inflammatory mediators by inhibiting NF-kB. Inflamm Res. 2009 Apr;58(4):198-203. | ||||
Ref 537435 | Optimization of the bioprocessing conditions for scale-up of transient production of a heterologous protein in plants using a chemically inducible viral amplicon expression system. Biotechnol Prog. 2009 May-Jun;25(3):722-34. | ||||
Ref 537654 | Inhibition of human neutrophil elastase by ICI 200,355. Eur J Pharmacol. 1991 Feb 7;193(2):153-8. | ||||
Ref 537900 | Neutrophil elastase inhibitor ICI 200,880 protects against attenuation of coronary flow reserve and myocardial dysfunction following temporary coronary artery occlusion in the dog. Cardiovasc Res. 1994 Jul;28(7):947-56. | ||||
Ref 537940 | Effect of a synthetic leukocyte elastase inhibitor on thrombin-induced pulmonary edema in the rat. Exp Lung Res. 1993 Mar-Apr;19(2):125-35. | ||||
Ref 538031 | Elastase contributes to antigen-induced mucociliary dysfunction in ovine airways. Am J Respir Crit Care Med. 1997 May;155(5):1522-8. | ||||
Ref 538111 | Neutrophil elastase promotes lung microvascular injury and proteolysis of endothelial cadherins. Am J Physiol. 1998 Aug;275(2 Pt 2):H385-92. | ||||
Ref 543602 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2358). | ||||
Ref 549133 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800032703) |
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