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

General Information of Drug (ID: DMT27QD)

• Drug Name: CHYMOSTATIN Drug Info
• Synonyms: Chymostatin; CHEMBL247767; AC1L9E22; MRXDGVXSWIXTQL-HYHFHBMOSA-N; C11308; 9076-44-2; SCHEMBL8259564; BDBM87059; CHEBI:510447; C31H41N7O6; BDBM222139; LS-187745; X6871; FT-0623815; (2S)-2-[[(1S)-2-[[(1S)-1-[[(1S)-1-benzyl-2-oxo-ethyl]carbamoyl]-3-methyl-butyl]amino]-1-(2-iminohexahydropyrimidin-4-yl)-2-oxo-ethyl]carbamoylamino]-3-phenyl-propanoic acid

Indication

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

• Cross-matching ID:
  PubChem CID: 443119
  ChEBI ID: CHEBI:510447
  CAS Number: CAS 9076-44-2
  TTD Drug ID: DMT27QD

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	[3]
JNJ-10311795	DM7OTQS	Chronic obstructive pulmonary disease	CA22	Phase 2	[4]
ASB17061	DMNVU28	Atopic dermatitis	EA80	Phase 2	[5]
BAY 11-42524	DM8SNEM	Left ventricular dysfunction	BD11	Phase 2	[6]
BAY 1142524	DMHKTGX	Myocardial infarction	BA41-BA43	Phase 2	[7]
2-(N-Morpholino)-Ethanesulfonic Acid	DMZVHSB	Discovery agent	N.A.	Investigative	[8]
Benzylsulfinic Acid	DM7XK28	Discovery agent	N.A.	Investigative	[9]
KM-01221	DMG594K	Cardiovascular disease	BA00-BE2Z	Investigative	[10]
Y-40613	DM412IV	Discovery agent	N.A.	Investigative	[11]
Rac-2q	DMD5TPH	Discovery agent	N.A.	Investigative	[1]

Drug(s) Affected By Kallikrein-8 (KLK8)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Panobinostat	DM58WKG	Chronic graft versus host disease		Approved	[12]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[13]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[14]
Potassium Chloride	DMMTAJC	Hypokalemia	5C77	Approved	[2]
Arsenic	DMTL2Y1	N. A.	N. A.	Approved	[15]
Magnesium	DMU4ORS	Ischemic stroke	8B11.5Z	Approved	[2]
Magnesium Sulfate	DMVEK07	Acute pain	MG31	Approved	[2]
Permethrin	DMZ0Q1G	Pediculus capitis infestation	1G00.0	Approved	[16]
Triclosan	DMZUR4N	Malaria	1F40-1F45	Approved	[17]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[18]

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
Kallikrein-8 (KLK8)	OTGVGHXY	KLK8_HUMAN	Gene/Protein Processing	[2]

References

• [1] 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.
• [2] Activation and enzymatic characterization of recombinant human kallikrein 8. Biol Chem. 2006 Jun;387(6):723-31. doi: 10.1515/BC.2006.091.
• [3] 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.
• [4] Discovery of potent, selective, orally active, nonpeptide inhibitors of human mast cell chymase. J Med Chem. 2007 Apr 19;50(8):1727-30.
• [5] Immunology of atopic eczema: overcoming the Th1/Th2 paradigm. Allergy. 2013 Aug;68(8):974-82.
• [6] 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.
• [7] 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.
• [8] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [9] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [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: 2340).
• [11] Therapeutic potential of a specific chymase inhibitor in atopic dermatitis. Jpn J Pharmacol. 2002 Nov;90(3):214-7.
• [12] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [13] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [14] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [15] Arsenic alters transcriptional responses to Pseudomonas aeruginosa infection and decreases antimicrobial defense of human airway epithelial cells. Toxicol Appl Pharmacol. 2017 Sep 15;331:154-163.
• [16] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [17] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [18] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.