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

General Information of Drug (ID: DM412IV)

• Drug Name: Y-40613 Drug Info
• Synonyms: CHEMBL281124; Y-40613; SCHEMBL7152045; BDBM50098847; 2-(2-{2-[5-Amino-2-(4-fluoro-phenyl)-6-oxo-6H-pyrimidin-1-yl]-acetylamino}-3-phenyl-propionyl)-benzooxazole-5-carboxylic acid methyl ester

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 9829503
  TTD Drug ID: DM412IV

Molecule-Related Drug Atlas

Drug(s) Targeting Chymase (CYM)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
SUN13834	DMPK34E	Gram-positive bacterial infection	1B74-1G40	Phase 2	[2]
JNJ-10311795	DM7OTQS	Chronic obstructive pulmonary disease	CA22	Phase 2	[3]
ASB17061	DMNVU28	Atopic dermatitis	EA80	Phase 2	[4]
BAY 11-42524	DM8SNEM	Left ventricular dysfunction	BD11	Phase 2	[5]
BAY 1142524	DMHKTGX	Myocardial infarction	BA41-BA43	Phase 2	[6]
2-(N-Morpholino)-Ethanesulfonic Acid	DMZVHSB	Discovery agent	N.A.	Investigative	[7]
Benzylsulfinic Acid	DM7XK28	Discovery agent	N.A.	Investigative	[8]
KM-01221	DMG594K	Cardiovascular disease	BA00-BE2Z	Investigative	[9]
Rac-2q	DMD5TPH	Discovery agent	N.A.	Investigative	[10]
Phenylalanylmethane	DMZNFT2	Discovery agent	N.A.	Investigative	[7]

Drug(s) Affected By Cathepsin G (CTSG)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[11]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[12]
Arsenic	DMTL2Y1	N. A.	N. A.	Approved	[13]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[14]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[15]
phorbol 12-myristate 13-acetate	DMJWD62	Acute myeloid leukaemia	2A60	Phase 2	[16]
Benzo(a)pyrene	DMN7J43	N. A.	N. A.	Phase 1	[17]
bisphenol A	DM2ZLD7	Discovery agent	N.A.	Investigative	[18]
fMet-Leu-Phe	DMQ391A	N. A.	N. A.	Investigative	[16]
Sulforaphane	DMQY3L0	Skin disease	EA00-EM0Z	Investigative	[19]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Chymase (CYM)	TT8VUE0	CMA1_HUMAN	Inhibitor	[1]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Cathepsin G (CTSG)	OT85ZMQG	CATG_HUMAN	Gene/Protein Processing	[1]

References

• [1] Therapeutic potential of a specific chymase inhibitor in atopic dermatitis. Jpn J Pharmacol. 2002 Nov;90(3):214-7.
• [2] Oral chymase inhibitor SUN13834 ameliorates skin inflammation as well as pruritus in mouse model for atopic dermatitis.Eur J Pharmacol.2008 Dec 28;601(1-3):186-91.
• [3] Discovery of potent, selective, orally active, nonpeptide inhibitors of human mast cell chymase. J Med Chem. 2007 Apr 19;50(8):1727-30.
• [4] Immunology of atopic eczema: overcoming the Th1/Th2 paradigm. Allergy. 2013 Aug;68(8):974-82.
• [5] ClinicalTrials.gov (NCT02452515) A Single-blind Pilot Study to Investigate Safety and Tolerability of the Chymase Inhibitor BAY1142524 in Clinically Stable Patients With Left-ventricular Dysfunction.
• [6] Pharmacokinetics, Safety, and Tolerability of the Novel Chymase Inhibitor BAY 1142524 in Healthy Male Volunteers. Clin Pharmacol Drug Dev. 2019 May;8(4):467-479.
• [7] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [8] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [9] 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: 2340).
• [10] Identification of 6-substituted 4-arylsulfonyl-1,4-diazepane-2,5-diones as a novel scaffold for human chymase inhibitors. Bioorg Med Chem Lett. 2007 Jun 15;17(12):3431-4.
• [11] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [12] Systems analysis of transcriptome and proteome in retinoic acid/arsenic trioxide-induced cell differentiation/apoptosis of promyelocytic leukemia. Proc Natl Acad Sci U S A. 2005 May 24;102(21):7653-8.
• [13] Fetal-sex dependent genomic responses in the circulating lymphocytes of arsenic-exposed pregnant women in New Hampshire. Reprod Toxicol. 2017 Oct;73:184-195. doi: 10.1016/j.reprotox.2017.07.023. Epub 2017 Aug 6.
• [14] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [15] Monitoring the gene expression profiles of doxorubicin-resistant acute myelocytic leukemia cells by DNA microarray analysis. Life Sci. 2006 Jun 6;79(2):193-202. doi: 10.1016/j.lfs.2005.12.054. Epub 2006 Feb 3.
• [16] The anti-inflammatory effect of 2-(4-hydroxy-3-prop-2-enyl-phenyl)-4-prop-2-enyl-phenol by targeting Lyn kinase in human neutrophils. Chem Biol Interact. 2015 Jul 5;236:90-101. doi: 10.1016/j.cbi.2015.05.004. Epub 2015 May 14.
• [17] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [18] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [19] Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.