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	[5]
Epigallocatechin gallate	DMCGWBJ	Hepatic fibrosis	DB93.0	Phase 3	[6]
Sivelestat	DM6BZCV	Crohn disease	DD70	Phase 3	[7]
Tiprelestat	DM1SB94	Myocardial infarction	BA41-BA43	Phase 2	[8]
AZD9668	DMB87M3	Bronchiectasis	CA24	Phase 2	[9]
L-694,458	DMA0DSJ	Cystic fibrosis	CA25	Phase 2	[2]
BAY 85-8501	DMCPUKG	Bronchiectasis	CA24	Phase 2	[10]
DX-890	DMBFZET	Acute lung injury	NB32.3	Phase 2	[5]
POL-6014	DM9B68S	Cystic fibrosis	CA25	Phase 1	[11]
AZD-9819	DMWYHXG	Chronic obstructive pulmonary disease	CA22	Phase 1	[12]

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	[13]
Losmapimod	DMIL37Z	Acute coronary syndrome	BA41	Phase 3	[13]
VX-702	DMKJDR6	Coronary artery disease	BA80	Phase 2a	[14]
VX-745	DMJAEG6	Alzheimer disease	8A20	Phase 2	[15]
Dilmapimod	DMBYJ92	Acute lung injury	NB32.3	Phase 2	[13]
PMID25991433-Compound-A1	DM89LF0	N. A.	N. A.	Patented	[16]
PMID25991433-Compound-F2	DM37VIQ	N. A.	N. A.	Patented	[16]
PMID25991433-Compound-L2	DM58UO9	N. A.	N. A.	Patented	[16]
PMID25991433-Compound-L3	DM3LWUR	N. A.	N. A.	Patented	[16]
PMID25991433-Compound-L1	DM2135Y	N. A.	N. A.	Patented	[16]

Drug(s) Affected By Interleukin-1 beta (IL1B)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[17]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[18]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[19]
Fexofenadine	DM17ONX	Allergic rhinitis	CA08.0	Approved	[20]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[21]
Lumiracoxib	DM1S4AG	Chronic renal failure	GB61.Z	Approved	[20]
Imiquimod	DM1TMA3	Alopecia areata	ED70.2	Approved	[22]
Selenium	DM25CGV	N. A.	N. A.	Approved	[23]
Ribavirin	DMEYLH9	Hepatitis C virus infection	1E51.1	Approved	[4]
Spironolactone	DM2AQ5N	Chronic heart failure	BD1Z	Approved	[24]

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]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Gene/Protein Processing	[4]

References

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• [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] Profiling the immunotoxicity of chemicals based on in vitro evaluation by a combination of the Multi-ImmunoTox assay and the IL-8 Luc assay. Arch Toxicol. 2018 Jun;92(6):2043-2054. doi: 10.1007/s00204-018-2199-7. Epub 2018 Mar 29.
• [5] Emerging therapies for treatment of acute lung injury and acute respiratory distress syndrome. Expert Opin Emerg Drugs. 2007 Sep;12(3):461-77.
• [6] Evaluation of human neutrophil elastase inhibitory effect of iridoid glycosides from Hedyotis diffusa. Bioorg Med Chem Lett. 2010 Jan 15;20(2):513-5.
• [7] Neutrophil elastase inhibitor (sivelestat) reduces the levels of inflammatory mediators by inhibiting NF-kB. Inflamm Res. 2009 Apr;58(4):198-203.
• [8] Company report (Proteo Biotech AG)
• [9] Clinical pipeline report, company report or official report of AstraZeneca (2009).
• [10] 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.
• [11] 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).
• [12] 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.
• [13] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [14] 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.
• [15] Pharmacological inhibitors of MAPK pathways. Trends Pharmacol Sci. 2002 Jan;23(1):40-5.
• [16] c-Jun N-terminal kinase inhibitors: a patent review (2010 - 2014).Expert Opin Ther Pat. 2015;25(8):849-72.
• [17] Cannabidiol Modulates the Immunophenotype and Inhibits the Activation of the Inflammasome in Human Gingival Mesenchymal Stem Cells. Front Physiol. 2016 Nov 24;7:559. doi: 10.3389/fphys.2016.00559. eCollection 2016.
• [18] ERE-independent ERalpha target genes differentially expressed in human breast tumors. Mol Cell Endocrinol. 2005 Dec 21;245(1-2):53-9. doi: 10.1016/j.mce.2005.10.003. Epub 2005 Nov 17.
• [19] Reactive metabolite of gefitinib activates inflammasomes: implications for gefitinib-induced idiosyncratic reaction. J Toxicol Sci. 2020;45(11):673-680. doi: 10.2131/jts.45.673.
• [20] An in vitro coculture system of human peripheral blood mononuclear cells with hepatocellular carcinoma-derived cells for predicting drug-induced liver injury. Arch Toxicol. 2021 Jan;95(1):149-168. doi: 10.1007/s00204-020-02882-4. Epub 2020 Aug 20.
• [21] Gypenosides protect retinal pigment epithelium cells from oxidative stress. Food Chem Toxicol. 2018 Feb;112:76-85.
• [22] (9)-Tetrahydrocannabinol Suppresses Monocyte-Mediated Astrocyte Production of Monocyte Chemoattractant Protein 1 and Interleukin-6 in a Toll-Like Receptor 7-Stimulated Human Coculture. J Pharmacol Exp Ther. 2019 Oct;371(1):191-201. doi: 10.1124/jpet.119.260661. Epub 2019 Aug 5.
• [23] Changes in gene expression profiles in response to selenium supplementation among individuals with arsenic-induced pre-malignant skin lesions. Toxicol Lett. 2007 Mar 8;169(2):162-76. doi: 10.1016/j.toxlet.2007.01.006. Epub 2007 Jan 19.
• [24] Spironolactone induces apoptosis in human mononuclear cells. Association between apoptosis and cytokine suppression. Apoptosis. 2006 Apr;11(4):573-9. doi: 10.1007/s10495-006-4919-3.