Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMRSOBG)

• Drug Name: Mdl 101,146 Drug Info
• Synonyms: UNII-2D08A509S3; CHEBI:45517; CHEMBL56852; 1-{3-METHYL-2-[4-(MORPHOLINE-4-CARBONYL)-BENZOYLAMINO]-BUTYRYL}-PYRROLIDINE-2-CARBOXYLIC ACID (3,3,4,4,4-PENTAFLUORO-1-ISOPROPYL-2-OXO-BUTYL)-AMIDE; 2D08A509S3; Mdl 101,146; N-[4-(morpholin-4-ylcarbonyl)benzoyl]-L-valyl-N-[(3S)-5,5,6,6,6-pentafluoro-2-methyl-4-oxohexan-3-yl]-L-prolinamide; N-{[4-(morpholin-4-ylcarbonyl)phenyl]carbonyl}-L-valyl-N-[(1S)-3,3,4,4,4-pentafluoro-1-(1-methylethyl)-2-oxobutyl]-L-prolinamide; MDL-101146, (S)-; AC1NRD4J; BDBM50058341; 163660-59-1

Indication

Disease Entry	ICD 11	Status	REF
Inflammation	1A00-CA43.1	Terminated	[1]

• Cross-matching ID:
  PubChem CID: 46936357
  CAS Number: CAS 149859-17-6
  TTD Drug ID: DMRSOBG

Molecule-Related Drug Atlas

Drug(s) Targeting Pancreatic elastase 1 (CELA1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Alpha 1-PI	DMXC1K9	Alpha-1 antitrypsin deficiency	5C5A	Approved	[3]
Erdosteine	DM6QFSV	Bronchitis	CA20	Approved	[4]
Sivelestat	DM6BZCV	Crohn disease	DD70	Phase 3	[5]
WIN-63759	DMRV48P	Emphysema	CA21	Terminated	[6]
SSR-69071	DMWL4MI	Chronic obstructive pulmonary disease	CA22	Terminated	[7]
SYN-1134	DMG2SQM	Cystic fibrosis	CA25	Terminated	[8]
PBI-1101	DMWD1RC	Inflammation	1A00-CA43.1	Terminated	[9]
Acetate Ion	DMD08RH	Discovery agent	N.A.	Investigative	[2]
Grassystatin a	DM1PWX2	Discovery agent	N.A.	Investigative	[10]
Dimethylformamide	DML6O4N	Discovery agent	N.A.	Investigative	[11]

Drug(s) Targeting Neutrophil elastase (NE)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sivelestat sodium hydrate	DMOSJD0	Acute lung injury	NB32.3	Phase 4	[12]
Epigallocatechin gallate	DMCGWBJ	Hepatic fibrosis	DB93.0	Phase 3	[13]
Sivelestat	DM6BZCV	Crohn disease	DD70	Phase 3	[14]
Tiprelestat	DM1SB94	Myocardial infarction	BA41-BA43	Phase 2	[15]
AZD9668	DMB87M3	Bronchiectasis	CA24	Phase 2	[16]
L-694,458	DMA0DSJ	Cystic fibrosis	CA25	Phase 2	[17]
BAY 85-8501	DMCPUKG	Bronchiectasis	CA24	Phase 2	[18]
DX-890	DMBFZET	Acute lung injury	NB32.3	Phase 2	[12]
POL-6014	DM9B68S	Cystic fibrosis	CA25	Phase 1	[19]
AZD-9819	DMWYHXG	Chronic obstructive pulmonary disease	CA22	Phase 1	[20]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Neutrophil elastase (NE)	TTPLTSQ	ELNE_HUMAN	Inhibitor	[2]
Pancreatic elastase 1 (CELA1)	TT3NKIB	CELA1_HUMAN	Inhibitor	[2]

References

• [1] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007771)
• [2] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [3] Elastase inhibitors. J Soc Biol. 2001;195(2):143-50.
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [5] 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.
• [6] 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.
• [7] Pivotal role for alpha1-antichymotrypsin in skin repair. J Biol Chem. 2011 Aug 19;286(33):28889-901.
• [8] EP patent application no. 1292314, Method for treating respiratory disorders associated with pulmonary elastic fiber injury comprising the use of glycosaminoglycans.
• [9] CN patent application no. 1813706, Use of elastic protease inhibitor for preparing medicine for protecting cerebral hemorrhage.
• [10] Grassystatins A-C from marine cyanobacteria, potent cathepsin E inhibitors that reduce antigen presentation. J Med Chem. 2009 Sep 24;52(18):5732-47.
• [11] Liver disease associated with occupational exposure to the solvent dimethylformamide. Ann Intern Med. 1988 May;108(5):680-6.
• [12] Emerging therapies for treatment of acute lung injury and acute respiratory distress syndrome. Expert Opin Emerg Drugs. 2007 Sep;12(3):461-77.
• [13] Evaluation of human neutrophil elastase inhibitory effect of iridoid glycosides from Hedyotis diffusa. Bioorg Med Chem Lett. 2010 Jan 15;20(2):513-5.
• [14] Neutrophil elastase inhibitor (sivelestat) reduces the levels of inflammatory mediators by inhibiting NF-kB. Inflamm Res. 2009 Apr;58(4):198-203.
• [15] Company report (Proteo Biotech AG)
• [16] Clinical pipeline report, company report or official report of AstraZeneca (2009).
• [17] Neutrophil elastase inhibitors as treatment for COPD. Expert Opin Investig Drugs. 2002 Jul;11(7):965-80.
• [18] 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.
• [19] URL: 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).
• [20] 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.