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

General Information of Drug (ID: DM1A2UI)

• Drug Name: PGX-200097 Drug Info
• Synonyms: COMT/dopamine D2 receptor inhibitors (schizophrenia), Psychiatric Genomics; Catechol-O-methyltransferase/dopamine D2 receptor inhibitors (schizophrenia), Psychiatric Genomics

Indication

Disease Entry	ICD 11	Status	REF
Schizophrenia	6A20	Preclinical	[1]

• Cross-matching ID: TTD Drug ID: DM1A2UI

Molecule-Related Drug Atlas

Drug(s) Targeting Dopamine D2 receptor (D2R)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dopamine	DMPGUCF	Acromegaly	5A60.0	Approved	[3]
Haloperidol	DM96SE0	Delirium		Approved	[4]
Perphenazine	DMA4MRX	Schizophrenia	6A20	Approved	[5]
Perazine	DM2AOTZ	Psychotic disorder	6A20-6A25	Approved	[6]
Domperidone	DMBDPY0	Gastrointestinal disease	DE2Z	Approved	[7]
Levodopa	DMN3E57	Parkinson disease	8A00.0	Approved	[8]
Quetiapine	DM1N62C	Anorexia nervosa cachexia	6B80	Approved	[9]
Pimozide	DMW83TP	Schizophrenia	6A20	Approved	[10]
Chlorpromazine	DMBGZI3	Acute intermittent hepatic porphyria	5C58.11	Approved	[11]
Iloperidone	DM6AUFY	Schizophrenia	6A20	Approved	[12]

Drug(s) Targeting Catechol-O-methyl-transferase (COMT)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Entacapone	DMLBVKQ	Parkinson disease	8A00.0	Approved	[13]
Opicapone	DM1BKA6	Parkinson disease	8A00.0	Approved	[14]
Tolcapone	DM8MNVO	Parkinson disease	8A00.0	Approved	[15]
BIA 3-202	DMG3ON2	Parkinson disease	8A00.0	Phase 2	[16]
CGP-28014	DMYNTQV	Major depressive disorder	6A70.3	Phase 2	[17]
Nitecapone	DMSJYEX	Pain	MG30-MG3Z	Discontinued in Phase 2	[18]
1-(3,4-dihydroxy-5-nitrophenyl)-2-phenoxyethanone	DMKI719	Discovery agent	N.A.	Investigative	[19]
7,8-dihydroxy-4-phenyl-2H-chromen-2-one	DMUB5E8	Discovery agent	N.A.	Investigative	[20]
3,5-Dinitrocatechol	DMBGSHD	Discovery agent	N.A.	Investigative	[21]
1-(3,4-dihydroxy-2-nitrophenyl)-2-phenylethanone	DM9M5D1	Discovery agent	N.A.	Investigative	[22]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Catechol-O-methyl-transferase (COMT)	TTKWFB8	COMT_HUMAN	Inhibitor	[2]
Dopamine D2 receptor (D2R)	TTEX248	DRD2_HUMAN	Inhibitor	[2]

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 800024498)
• [2] Schizophrenia, "just the facts" 5. Treatment and prevention. Past, present, and future. Schizophr Res. 2010 Sep;122(1-3):1-23.
• [3] The Detection of Dopamine Gene Receptors (DRD1-DRD5) Expression on Human Peripheral Blood Lymphocytes by Real Time PCR. Iran J Allergy Asthma Immunol. 2004 Dec;3(4):169-74.
• [4] Dopaminergic synapses in the matrix of the ventrolateral striatum after chronic haloperidol treatment. Synapse. 2002 Aug;45(2):78-85.
• [5] CYP2D6 and DRD2 genes differentially impact pharmacodynamic sensitivity and time course of prolactin response to perphenazine. Pharmacogenet Genomics. 2007 Nov;17(11):989-93.
• [6] Synthesis and in vitro binding of N-phenyl piperazine analogs as potential dopamine D3 receptor ligands. Bioorg Med Chem. 2005 Jan 3;13(1):77-87.
• [7] Screening of domperidone in wastewater by high performance liquid chromatography and solid phase extraction methods. Talanta. 2006 Jan 15;68(3):928-31.
• [8] 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. (Ligand id: 3639).
• [9] Receptor reserve-dependent properties of antipsychotics at human dopamine D2 receptors. Eur J Pharmacol. 2009 Apr 1;607(1-3):35-40.
• [10] [The benzamides tiapride, sulpiride, and amisulpride in treatment for Tourette's syndrome]. Nervenarzt. 2007 Mar;78(3):264, 266-8, 270-1.
• [11] Modulatory role of dopamine D2 receptors and fundamental role of L-type Ca2+ channels in the induction of long-term potentiation in the basolateral... Eur J Pharmacol. 2009 Mar 15;606(1-3):90-3.
• [12] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [13] Entacapone: a catechol-O-methyltransferase inhibitor for the adjunctive treatment of Parkinson's disease. Clin Ther. 2001 Jun;23(6):802-32; discussion 771.
• [14] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [15] Catechol-O-methyltransferase inhibitors in the management of Parkinson's disease. Semin Neurol. 2001;21(1):15-22.
• [16] Chemical synthesis and characterization of conjugates of a novel catechol-O-methyltransferase inhibitor. Bioconjug Chem. 2002 Sep-Oct;13(5):1112-8.
• [17] CGP 28014, a new inhibitor of cerebral catechol-O-methylation with a non-catechol structure. Naunyn Schmiedebergs Arch Pharmacol. 1990 Sep;342(3):305-11.
• [18] Effect of a novel catechol-O-methyltransferase inhibitor, nitecapone, on the metabolism of L-dopa in healthy volunteers. Clin Neuropharmacol. 1990 Oct;13(5):436-47.
• [19] Synthesis, biological evaluation, and molecular modeling studies of a novel, peripherally selective inhibitor of catechol-O-methyltransferase. J Med Chem. 2004 Dec 2;47(25):6207-17.
• [20] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [21] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [22] Synthesis and biological evaluation of a novel series of "ortho-nitrated" inhibitors of catechol-O-methyltransferase. J Med Chem. 2005 Dec 15;48(25):8070-8.