Therapeutic Targets Database
BIDD Pharmainformatics Databases
 
   
   

 

TTD Target ID: TTDS00448

Target Information
NameLeukocyte elastase    
Type of targetSuccessful target    
SynonymsBone marrow serine protease    
Medullasin    
Neutrophil elastase    
PMN elastase    
DiseaseAdult respiratory distress syndrome
[ICD9: 518.5, 518.82   ICD10: J80]
[1]
Allergic rhinitis, unspecified
[ICD9: 472.0, 477, 995.3   ICD10: J00, J30, J31.0, T78.4]
[2]
Asthma
[ICD9: 493   ICD10: J45]
[3][4][5]
Attenuated coronary flow reserve and myocardial dysfunction
[ICD9: 410   ICD10: I21, I22]
[6]
Chronic bronchitis
[ICD9: 491   ICD10: J42]
[5]
Chronic obstructive pulmonary disease, unspecified
[ICD9: 460-519, 490-492, 494-496   ICD10: J00-J99, J40-J44, J47]
[7][1]
Cystic fibrosis
[ICD9: 277.0   ICD10: E84]
[1][8][5]
Emphysema
[ICD9: 492   ICD10: J43]
[1]
Intestinal ischemia-reperfusion associated with lung injury and the acute respiratory distress syndrome[9]
Mucociliary dysfunction[10]
Pulmonary edema (thrombin-induced)
[ICD9: 782.3   ICD10: R60.9]
[11]
Drug(s)Alpha-1-proteinase inhibitorApprovedPanacinar emphysema[12]
Sivelestat sodium hydratePhase IV completedAcute ling injury/Acute respiratory distress syndrome; [13]
DX-890Phase II completedAcute ling injury/Acute respiratory distress syndrome; cystic fibrosis[13]
AZD9668Phase IICOPD[14]
DermolastinPhase IIAtopic Dermatitis, Alpha 1 Antitrypsin Deficiency[15][16][17][18]
BAY 85-8501Phase IBronchiectasis
DermolastinHalted in Phase IChronic Obstructive Pulmonary Disease[15][16][17][18]
DermolastinHalted in Phase IEmphysema[15][16][17][18]
BioChemical ClassHydrolases acting on peptide bonds (Peptidases)    
EC NumberEC 3.4.21.37
PathwaySystemic lupus erythematosus
UniProt IDP08246
PDB Structure1B0F; 1H1B; 1HNE; 1PPF; 1PPG; 2RG3; 2Z7F; 3Q76; 3Q77.    
FunctionMedullasin modifies the functions of natural killer cells, monocytes and granulocytes.    
SequenceMTLGRRLACLFLACVLPALLLGGTALASEIVGGRRARPHAWPFMVSLQLRGGHFCGATLI APNFVMSAAHCVANVNVRAVRVVLGAHNLSRREPTRQVFAVQRIFENGYDPVNLLNDIVI LQLNGSATINANVQVAQLPAQGRRLGNGVQCLAMGWGLLGRNRGIASVLQELNVTVVTSL CRRSNVCTLVRGRQAGVCFGDSGSPLVCNGLIHGIASFVRGGCASGLYPDAFAPVAQFVN WIDSIIQRSEDNPCPHPRDPDPASRTH
Related US Patent6,215,002
6,228,853
6,375,926
6,548,638
6,608,175
6,656,911
Target ValidationClick to Find Target Validation Information.    
Inhibitor (1H-pyrazol-1-yl)[19]
(3,4-dichlorophenyl)[19]
(3-nitro-1H-pyrazol-1-yl)[19]
(3-nitro-1H-pyrazol-1-yl)[19]
(4-bromo-1H-pyrazol-1-yl)[19]
(4-bromo-1H-pyrazol-1-yl)[19]
(4-bromo-1H-pyrazol-1-yl)[19]
(4-chloro-1H-pyrazol-1-yl)[19]
(4-nitro-1H-pyrazol-1-yl)[19]
(4-nitro-1H-pyrazol-1-yl)[19]
1- (3,3-Dimethyl-2-oxo-butyl)-1H-indole-2,3-dione[20]
1-benzoyl-N-phenyl-1H-pyrazole-3-carboxamide[19]
1-benzyl-3,3-diethylazetidine-2,4-dione[21]
1-benzyl-3,3-dimethylazetidine-2,4-dione[21]
2-methylbut-3-yn-2-yl 4-methoxybenzoate[19]
3,3-Diethyl-1- (pyridin-3-yl)azetidine-2,4-dione[21]
3,3-Diethyl-1-o-tolylazetidine-2,4-dione[21]
3,3-diethyl-1-phenylazetidine-2,4-dione[21]
3,4-dichloroisocoumarin[22]
3-Benzyl-3-ethyl-1-phenylazetidine-2,4-dione[21]
3-Benzyl-3-methyl-1-phenylazetidine-2,4-dione[21]
3-Decanoyl-4-hydroxy-6-nonyl-pyran-2-one[23]
3-Ethyl-3-isobutyl-1-phenylazetidine-2,4-dione[21]
3-butyl-3-ethyl-1-phenylazetidine-2,4-dione[21]
4-Hydroxy-3-nonanoyl-6-octyl-pyran-2-one[23]
4-methoxy-N'- (2-phenylacetyl)benzohydrazide[19]
6-Heptyl-4-hydroxy-3-octanoyl-pyran-2-one[23]
AE-3763[7]
AZD9668[14]
Ac-Ala-Pro-Val- (2-benzoxazole)[24]
Alpha-1-proteinase inhibitor[12]
CE-1037[7]
CEP-18770[25]
Cbz-Val-Pro-Val- (2-benzoxazole)[24]
DX-890[13]
Dermolastin[15][16][17][18]
E-6-O-p-methoxycinnamoyl scandoside methyl ester[26]
EPIGALOCATECHIN GALLATE[26]
FK-706[7]
FR-901277[27]
FR-901451[27]
Fucose[28]
GW-311616[7]
ICI 200,355[3][2][10][11][5]
ICI 200,880[7][6]
ICI-200355[29]
ICI-200880[30]
L-658,758[9]
L-658758[29]
L-694,458[7]
MR-889[7]
Mdl 101,146[28]
N,N-bis (cyanomethyl)-3,4-dimethoxybenzamide[19]
ONO-6818[7]
ONO-6818[31]
Secretory leukocyte protease inhibitor[8]
Sivelestat[32]
Sivelestat sodium hydrate[13]
TEI-8362[7]
Ulinastatin[33]
WIN-63395[34]
ZD-0892[7]
ZD-8321[7]
ZK-814048[35]
bornyl (3,4,5-trihydroxy)-cinnamate[36]
MultitargetDermolastin[15][16][17][18]
AptamerDD7[37]
ED1[37]
ED45[37]
Cross References 3D Structure
Related Literature
On-Line Medical Dictionary
Ref 1Inhaled porcine pancreatic elastase causes bronchoconstriction via a bradykinin-mediated mechanism. J Appl Physiol. 2000 Oct;89(4):1397-402. To Reference
Ref 2LTB(4)-induced nasal gland serous cell secretion mediated by neutrophil elastase. Am J Respir Crit Care Med. 1999 Aug;160(2):411-4. To Reference
Ref 3Role of neutrophil elastase in hypersecretion in asthma. Eur Respir J. 1999 Jan;13(1):190-6. To Reference
Ref 4Goblet cell degranulation after antigen challenge in sensitized guinea pigs. Role of neutrophils. Am J Respir Crit Care Med. 1998 Oct;158(4):1253-8. To Reference
Ref 5Inhibition of human neutrophil elastase by ICI 200,355. Eur J Pharmacol. 1991 Feb 7;193(2):153-8. To Reference
Ref 6Neutrophil 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. To Reference
Ref 7Neutrophil elastase inhibitors as treatment for COPD. Expert Opin Investig Drugs. 2002 Jul;11(7):965-80. To Reference
Ref 8Proteinase 3, a potent secretagogue in airways, is present in cystic fibrosis sputum. Am J Respir Cell Mol Biol. 1999 Apr;20(4):729-36. To Reference
Ref 9Neutrophil elastase promotes lung microvascular injury and proteolysis of endothelial cadherins. Am J Physiol. 1998 Aug;275(2 Pt 2):H385-92. To Reference
Ref 10Elastase contributes to antigen-induced mucociliary dysfunction in ovine airways. Am J Respir Crit Care Med. 1997 May;155(5):1522-8. To Reference
Ref 11Effect of a synthetic leukocyte elastase inhibitor on thrombin-induced pulmonary edema in the rat. Exp Lung Res. 1993 Mar-Apr;19(2):125-35. To Reference
Ref 12Interactions of alpha(1)-proteinase inhibitor with small ligands of therapeutic potential: binding with retinoic acid. Amino Acids. 2009 Jun 3. [Epub ahead of print] To Reference
Ref 13Emerging therapies for treatment of acute lung injury and acute respiratory distress syndrome. Expert Opin Emerg Drugs. 2007 Sep;12(3):461-77. To Reference
Ref 14AstraZeneca. Product Development Pipeline. January 29 2009. To Reference
Ref 15Arriva-ProMetic recombinant alpha 1-antitrypsin (rAAT) moves into the clinic for dermatology applications. ProMetic Life Sciences. 2009 To Reference
Ref 16rAAt (inhaled) Arriva/Hyland Immuno. Curr Opin Mol Ther. 2006 Feb;8(1):76-82. To Reference
Ref 17Optimization 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. To Reference
Ref 18Bioreactor 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. To Reference
Ref 19J Med Chem. 2007 Oct 4;50(20):4928-38. Epub 2007 Sep 12.N-benzoylpyrazoles are novel small-molecule inhibitors of human neutrophil elastase. To Reference
Ref 20Bioorg Med Chem Lett. 2000 Nov 20;10(22):2501-4.Parallel synthesis of isatin-based serine protease inhibitors. To Reference
Ref 21J 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. To Reference
Ref 22Antimicrob 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. To Reference
Ref 23J Med Chem. 1987 Jun;30(6):1017-23.Inhibition of human sputum elastase by substituted 2-pyrones. To Reference
Ref 24Bioorg 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. To Reference
Ref 25J Med Chem. 2008 Feb 28;51(4):1068-72. Epub 2008 Feb 5.Discovery of a potent, selective, and orally active proteasome inhibitor for the treatment of cancer. To Reference
Ref 26Bioorg 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. To Reference
Ref 27Bioorg 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. To Reference
Ref 28Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. To Reference
Ref 29Bioorg. Med. Chem. Lett. 5(4):319-324 (1995) To Reference
Ref 30J Med Chem. 1994 Dec 23;37(26):4538-53.Inhibition of human neutrophil elastase with peptidyl electrophilic ketones. 2. Orally active PG-Val-Pro-Val pentafluoroethyl ketones. To Reference
Ref 31Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. To Reference
Ref 32Inflamm Res. 2009 Apr;58(4):198-203.Neutrophil elastase inhibitor (sivelestat) reduces the levels of inflammatory mediators by inhibiting NF-kB. To Reference
Ref 33Effects of a protease inhibitor, ulinastatin, on coagulation and fibrinolysis in abdominal surgery. J Anesth. 2006;20(3):179-82. To Reference
Ref 34Bioorg. Med. Chem. Lett. 6(24):2941-2946 (1996) To Reference
Ref 35J Med Chem. 2007 Jun 28;50(13):2967-80. Epub 2007 May 31.Thiophene-anthranilamides as highly potent and orally available factor Xa inhibitors. To Reference
Ref 36Bioorg 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. To Reference
Ref 37Therapeutic applications of aptamers. Expert Opin Investig Drugs. 2008 Jan;17(1):43-60. To Reference



 

Welcome to sign our Guestbook.

If you find any error in data or bug in web service, please kindly report it to Dr. Zhu.


Dr. Chen Yuzong
Deputy Director of Center for Computational Science and Engineering
Professor in Department of Pharmacy
National University of Singapore, Singapore


All rights reserved.

   
 
 
Computer-aided Drug Design
about BIDD |  databases |  software |  teaching |  research |  links

 

Department of Computational Science | National University of Singapore | Blk S17, 3 Science Drive 2, Singapore 117543