Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT3NKIB)

• DTT Name: Pancreatic elastase 1 (CELA1)
• Synonyms: Elastase; CELA1
• Gene Name: CELA1
• DTT Type: Successful target; [1]
• Related Disease:
  Alpha-1-antitrypsin deficiency [ICD-11: 5C5A]
  Bronchitis [ICD-11: CA20]
• BioChemical Class: Peptidase
• UniProt ID: CELA1_HUMAN
• TTD ID: T22839
• EC Number: EC 3.4.21.36
• Sequence:
  MLVLYGHSTQDLPETNARVVGGTEAGRNSWPSQISLQYRSGGSRYHTCGGTLIRQNWVMT
  AAHCVDYQKTFRVVAGDHNLSQNDGTEQYVSVQKIVVHPYWNSDNVAAGYDIALLRLAQS
  VTLNSYVQLGVLPQEGAILANNSPCYITGWGKTKTNGQLAQTLQQAYLPSVDYAICSSSS
  YWGSTVKNTMVCAGGDGVRSGCQGDSGGPLHCLVNGKYSVHGVTSFVSSRGCNVSRKPTV
  FTQVSAYISWINNVIASN
• Function: Acts upon elastin.

Molecular Interaction Atlas (MIA) of This DTT

2 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Alpha 1-PI	DMXC1K9	Alpha-1 antitrypsin deficiency	5C5A	Approved	[2]
Erdosteine	DM6QFSV	Bronchitis	CA20	Approved	[1]

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sivelestat	DM6BZCV	Crohn disease	DD70	Phase 3	[3]

5 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Mdl 101,146	DMRSOBG	Inflammation	1A00-CA43.1	Terminated	[4]
PBI-1101	DMWD1RC	Inflammation	1A00-CA43.1	Terminated	[5]
SSR-69071	DMWL4MI	Chronic obstructive pulmonary disease	CA22	Terminated	[6]
SYN-1134	DMG2SQM	Cystic fibrosis	CA25	Terminated	[7]
WIN-63759	DMRV48P	Emphysema	CA21	Terminated	[8]

9 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(2-BROMOETHYL)(2-'FORMYL-4'-AMINOPHENYL) ACETATE	DMZSP7F	Discovery agent	N.A.	Investigative	[9]
(Tert-Butyloxycarbonyl)-Alanyl-Alanyl-Amine	DMLW7TV	Discovery agent	N.A.	Investigative	[4]
Acetate Ion	DMD08RH	Discovery agent	N.A.	Investigative	[4]
Acetyl-Ala-Ala-Pro-Ala-trifluromethane	DMFZJRN	Discovery agent	N.A.	Investigative	[10]
Acetyl-Pro-Ala-Pro-Ala-trifluoro methane	DMN5Z0F	Discovery agent	N.A.	Investigative	[10]
Dimethylformamide	DML6O4N	Discovery agent	N.A.	Investigative	[11]
Grassystatin a	DM1PWX2	Discovery agent	N.A.	Investigative	[12]
MOLASSAMIDE	DM0OWTS	Discovery agent	N.A.	Investigative	[13]
Para-Isopropylaniline	DMZY41U	Discovery agent	N.A.	Investigative	[4]

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	8.56E-02	0.06	0.25
Chronic obstructive pulmonary disease	CA23	Small airway epithelium	3.82E-02	0.19	0.7

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [2] Elastase inhibitors. J Soc Biol. 2001;195(2):143-50.
• [3] Sivelestat (selective neutrophil elastase inhibitor) improves the mortality rate of sepsis associated with both acute respiratory distress syndrome... Shock. 2010 Jan;33(1):14-8.
• [4] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [5] CN patent application no. 1813706, Use of elastic protease inhibitor for preparing medicine for protecting cerebral hemorrhage.
• [6] Pivotal role for alpha1-antichymotrypsin in skin repair. J Biol Chem. 2011 Aug 19;286(33):28889-901.
• [7] EP patent application no. 1292314, Method for treating respiratory disorders associated with pulmonary elastic fiber injury comprising the use of glycosaminoglycans.
• [8] Biological activity of WIN 63759, an orally bioavailable inhibitor of human neutrophil elastase. Drug Development Research Volume 34, Issue 3, pages 306-316, March 1995.
• [9] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [10] Synthesis of peptidyl fluoromethyl ketones and peptidyl alpha-keto esters as inhibitors of porcine pancreatic elastase, human neutrophil elastase, ... J Med Chem. 1990 Jan;33(1):394-407.
• [11] Liver disease associated with occupational exposure to the solvent dimethylformamide. Ann Intern Med. 1988 May;108(5):680-6.
• [12] Grassystatins A-C from marine cyanobacteria, potent cathepsin E inhibitors that reduce antigen presentation. J Med Chem. 2009 Sep 24;52(18):5732-47.
• [13] Molassamide, a depsipeptide serine protease inhibitor from the marine cyanobacterium Dichothrix utahensis. J Nat Prod. 2010 Mar 26;73(3):459-62.