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

General Information of Drug (ID: DMPK34E)

• Drug Name: SUN13834 Drug Info
• Synonyms: Trifluperidol; Trisedil; Triperidol; Psychoperidol; Flumoperone; Psicoperidol; Trisedyl; Psicoperidol-R; McN-JR-2498; 749-13-3; Trifluperidolo; Trifluperidolo [DCIT]; R-2498; Trifluperidolo [Italian]; Trifluperidolum [INN-Latin]; NSC 170978; UNII-R8869Q7R8I; Trifluperidol [USAN:INN:BAN]; P 459; BRN 1556208; CHEMBL15023; 1-Butanone, 1-(4-fluorophenyl)-4-(4-hydroxy-4-(3-(trifluoromethyl)phenyl)-1-piperidinyl)-; GPMXUUPHFNMNDH-UHFFFAOYSA-N; R8869Q7R8I; NSC170978; Triperidol (TN)

Indication

Disease Entry	ICD 11	Status	REF
Gram-positive bacterial infection	1B74-1G40	Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 5567
  ChEBI ID: CHEBI:135662
  CAS Number: CAS 749-13-3
  TTD Drug ID: DMPK34E
  INTEDE Drug ID: DR1642

Molecule-Related Drug Atlas

Drug(s) Targeting Chymase (CYM)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
JNJ-10311795	DM7OTQS	Chronic obstructive pulmonary disease	CA22	Phase 2	[5]
ASB17061	DMNVU28	Atopic dermatitis	EA80	Phase 2	[6]
BAY 11-42524	DM8SNEM	Left ventricular dysfunction	BD11	Phase 2	[7]
BAY 1142524	DMHKTGX	Myocardial infarction	BA41-BA43	Phase 2	[8]
2-(N-Morpholino)-Ethanesulfonic Acid	DMZVHSB	Discovery agent	N.A.	Investigative	[9]
Benzylsulfinic Acid	DM7XK28	Discovery agent	N.A.	Investigative	[10]
KM-01221	DMG594K	Cardiovascular disease	BA00-BE2Z	Investigative	[11]
Y-40613	DM412IV	Discovery agent	N.A.	Investigative	[12]
Rac-2q	DMD5TPH	Discovery agent	N.A.	Investigative	[13]
Phenylalanylmethane	DMZNFT2	Discovery agent	N.A.	Investigative	[9]

Drug(s) Targeting Phosphodiesterase 4 (PDE4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Apremilast	DMTWS9E	Psoriasis vulgaris	EA90	Approved	[14]
Oxtriphylline	DMLHSE3	Cough	MD12	Approved	[15]
Roflumilast	DMPGHY8	Asthma	CA23	Approved	[16]
Ibudilast	DM4LSPN	Castleman's disease	4B2Y	Approved	[17]
crisaborole	DMNVKU6	Atopic dermatitis	EA80	Approved	[18]
Arofylline	DM84AD1	Chronic obstructive pulmonary disease	CA22	Phase 3	[19]
ARQ-151	DML61S4	Atopic dermatitis	EA80	Phase 3	[20]
ONO-6126	DMRT28X	Chronic obstructive pulmonary disease	CA22	Phase 2	[19]
E6005	DM1S489	Atopic dermatitis	EA80	Phase 2	[21]
IC-485	DMB1UYV	Chronic obstructive pulmonary disease	CA22	Phase 2	[19]

Drug(s) Metabolized By Cytochrome P450 2D6 (CYP2D6)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[22]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[23]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[24]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[25]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[26]
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[27]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[28]
Dopamine	DMPGUCF	Acromegaly	5A60.0	Approved	[29]
Nicotine	DMWX5CO	Lung cancer	2C25.0	Approved	[30]
Propranolol	DM79NTF	Angina pectoris	BA40	Approved	[31]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Chymase (CYM)	TT8VUE0	CMA1_HUMAN	Modulator	[2]
Phosphodiesterase 4 (PDE4)	TTV5CGO	NOUNIPROTAC	Inhibitor	[3]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2D6 (CYP2D6) Main DME	DECB0K3	CP2D6_HUMAN	Substrate	[4]

References

• [1] Emerging drugs for bacterial urinary tract infections. Expert Opin Emerg Drugs. 2005 May;10(2):275-98.
• [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] Ocular hypotension induced by topical dopaminergic drugs and phosphodiesterase inhibitors. Eur J Pharmacol. 1994 Jun 2;258(1-2):85-94.
• [4] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
• [5] Discovery of potent, selective, orally active, nonpeptide inhibitors of human mast cell chymase. J Med Chem. 2007 Apr 19;50(8):1727-30.
• [6] Immunology of atopic eczema: overcoming the Th1/Th2 paradigm. Allergy. 2013 Aug;68(8):974-82.
• [7] 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.
• [8] 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.
• [9] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [10] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [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: 2340).
• [12] Therapeutic potential of a specific chymase inhibitor in atopic dermatitis. Jpn J Pharmacol. 2002 Nov;90(3):214-7.
• [13] 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.
• [14] Highly selective phosphodiesterase 4 inhibitors for the treatment of allergic skin diseases and psoriasis. Inflamm Allergy Drug Targets. 2007 Mar;6(1):17-26.
• [15] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [16] 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
• [17] Therapeutic targeting of 3',5'-cyclic nucleotide phosphodiesterases: inhibition and beyond. Nat Rev Drug Discov. 2019 Oct;18(10):770-796.
• [18] 2016 FDA drug approvals. Nat Rev Drug Discov. 2017 Feb 2;16(2):73-76.
• [19] Emerging drugs for the treatment of chronic obstructive pulmonary disease. Expert Opin Emerg Drugs. 2006 May;11(2):275-91.
• [20] Trial of Roflumilast Cream for Chronic Plaque Psoriasis. N Engl J Med. 2020 Jul 16;383(3):229-239.
• [21] Antipruritic effect of the topical phosphodiesterase 4 inhibitor E6005 ameliorates skin lesions in a mouse atopic dermatitis model. J Pharmacol Exp Ther. 2013 Jul;346(1):105-12.
• [22] Inhibitory effects of anticancer drugs on dextromethorphan-O-demethylase activity in human liver microsomes. Cancer Chemother Pharmacol. 1993;32(6):491-5.
• [23] Effect of genetic polymorphism on the metabolism of endogenous neuroactive substances, progesterone and p-tyramine, catalyzed by CYP2D6. Brain Res Mol Brain Res. 2004 Oct 22;129(1-2):117-23.
• [24] CYP2D6 polymorphisms and tamoxifen metabolism: clinical relevance. Curr Oncol Rep. 2010 Jan;12(1):7-15.
• [25] Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
• [26] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
• [27] Inhibition of cytochrome P450 2D6: structure-activity studies using a series of quinidine and quinine analogues. Chem Res Toxicol. 2003 Apr;16(4):450-9.
• [28] Effects of propofol on human hepatic microsomal cytochrome P450 activities. Xenobiotica. 1998 Sep;28(9):845-53.
• [29] Pharmacogenetics of schizophrenia. Am J Med Genet. 2000 Spring;97(1):98-106.
• [30] Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol. 1999 Mar;73(2):65-70.
• [31] Structure-activity relationship for human cytochrome P450 substrates and inhibitors. Drug Metab Rev. 2002 Feb-May;34(1-2):69-82.