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

General Information of Drug (ID: DM69OR8)

• Drug Name: FR167653 Drug Info
• Synonyms: HMPQTEPEMQZWQH-ROUUACIJSA-N; 2-(5-AMINO-6-OXO-2-PHENYL-6H-PYRIMIDIN-1-YL)-N-[2-(5-TERT-BUTYL-1,3,4-OXADIAZOL-2-YL)-1-(METHYLETHYL)-2-HYDROXYETHYL]ACETAMIDE; AC1NR9VL; SCHEMBL15034365; 2-(5-amino-6-oxo-2-phenylpyrimidin-1-yl)-N-[(1S,2S)-1-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-1-hydroxy-3-methylbutan-2-yl]acetamide; ONO-6818

Indication

Disease Entry	ICD 11	Status	REF
Chronic obstructive pulmonary disease	CA22	Discontinued in Phase 1	[1]

• Cross-matching ID:
  PubChem CID: 135484078
  CAS Number: CAS 158876-66-5
  TTD Drug ID: DM69OR8

Molecule-Related Drug Atlas

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

Drug(s) Targeting Stress-activated protein kinase 2a (p38 alpha)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ozagrel	DMIGKA1	Xerophthalmia	5B55.Y	Phase 4	[12]
Losmapimod	DMIL37Z	Acute coronary syndrome	BA41	Phase 3	[12]
VX-702	DMKJDR6	Coronary artery disease	BA80	Phase 2a	[13]
VX-745	DMJAEG6	Alzheimer disease	8A20	Phase 2	[14]
Dilmapimod	DMBYJ92	Acute lung injury	NB32.3	Phase 2	[12]
PMID25991433-Compound-A1	DM89LF0	N. A.	N. A.	Patented	[15]
PMID25991433-Compound-F2	DM37VIQ	N. A.	N. A.	Patented	[15]
PMID25991433-Compound-L2	DM58UO9	N. A.	N. A.	Patented	[15]
PMID25991433-Compound-L3	DM3LWUR	N. A.	N. A.	Patented	[15]
PMID25991433-Compound-L1	DM2135Y	N. A.	N. A.	Patented	[15]

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]
Stress-activated protein kinase 2a (p38 alpha)	TTQBR95	MK14_HUMAN	Inhibitor	[3]

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 800012873)
• [2] Neutrophil elastase inhibitors as treatment for COPD. Expert Opin Investig Drugs. 2002 Jul;11(7):965-80.
• [3] Prevention of the onset and progression of collagen-induced arthritis in rats by the potent p38 mitogen-activated protein kinase inhibitor FR167653. Arthritis Rheum. 2003 Sep;48(9):2670-81.
• [4] Emerging therapies for treatment of acute lung injury and acute respiratory distress syndrome. Expert Opin Emerg Drugs. 2007 Sep;12(3):461-77.
• [5] Evaluation of human neutrophil elastase inhibitory effect of iridoid glycosides from Hedyotis diffusa. Bioorg Med Chem Lett. 2010 Jan 15;20(2):513-5.
• [6] Neutrophil elastase inhibitor (sivelestat) reduces the levels of inflammatory mediators by inhibiting NF-kB. Inflamm Res. 2009 Apr;58(4):198-203.
• [7] Company report (Proteo Biotech AG)
• [8] Clinical pipeline report, company report or official report of AstraZeneca (2009).
• [9] 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.
• [10] 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).
• [11] 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.
• [12] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [13] Efficacy, pharmacodynamics, and safety of VX-702, a novel p38 MAPK inhibitor, in rheumatoid arthritis: results of two randomized, double-blind, placebo-controlled clinical studies. Arthritis Rheum. 2009 May;60(5):1232-41.
• [14] Pharmacological inhibitors of MAPK pathways. Trends Pharmacol Sci. 2002 Jan;23(1):40-5.
• [15] c-Jun N-terminal kinase inhibitors: a patent review (2010 - 2014).Expert Opin Ther Pat. 2015;25(8):849-72.