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

General Information of Drug (ID: DMZ4237)

• Drug Name: 4-(4-Benzyl-piperazin-1-yl)-5-chloro-1H-indole Drug Info
• Synonyms: CHEMBL311539; 4-(4-Benzyl-piperazin-1-yl)-5-chloro-1H-indole

Indication

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

• Cross-matching ID:
  PubChem CID: 44323978
  TTD Drug ID: DMZ4237

Molecule-Related Drug Atlas

Drug(s) Targeting Dopamine D3 receptor (D3R)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cariprazine	DMJYDVK	Bipolar disorder	6A60	Approved	[2]
Pramipexole	DMNMW9R	Parkinson disease	8A00.0	Approved	[3]
Ropinirole	DMA6S1D	Parkinson disease	8A00.0	Approved	[3]
CM-2395	DMASPWR	Schizophrenia	6A20	Phase 3	[4]
P2B-001	DM9PVHX	Parkinson disease	8A00.0	Phase 3	[5]
RP5063	DMKUE8O	Schizophrenia	6A20	Phase 2	[6]
ONC201	DMM5SCF	Endometrial cancer	2C76	Phase 2	[7]
TAK-906	DMBQD9H	Diabetic gastroparesis	DA41.00	Phase 2	[8]
GSK598809	DMGU05N	Drug abuse	6C4G.1Z	Phase 2	[9]
GSK618334	DMJPXZ4	Drug abuse	6C4G.1Z	Phase 1	[9]

Drug(s) Targeting Dopamine D4 receptor (D4R)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Clozapine	DMFC71L	Schizophrenia	6A20	Approved	[3]
Phenyltoloxamine	DMKAEQW	Allergy	4A80-4A85	Approved	[10]
CM-2395	DMASPWR	Schizophrenia	6A20	Phase 3	[4]
RP5063	DMKUE8O	Schizophrenia	6A20	Phase 2	[6]
L-745,870	DMTGR25	Psychotic disorder	6A20-6A25	Phase 2	[11]
NGD 94-1	DMM1Y8F	Schizophrenia	6A20	Phase 1	[12]
ABT-724	DMDQVY4	Erectile dysfunction	HA01.1	Discontinued in Phase 2	[13]
Lu-35138	DMQ7A35	Psychotic disorder	6A20-6A25	Discontinued in Phase 2	[14]
NGD-94-4	DMZ9WLO	Schizophrenia	6A20	Discontinued in Phase 1	[15]
PD-165167	DMD0GB4	Schizophrenia	6A20	Preclinical	[12]

Drug(s) Targeting Dopamine D2 receptor (D2R)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dopamine	DMPGUCF	Acromegaly	5A60.0	Approved	[16]
Haloperidol	DM96SE0	Delirium		Approved	[17]
Perphenazine	DMA4MRX	Schizophrenia	6A20	Approved	[18]
Perazine	DM2AOTZ	Psychotic disorder	6A20-6A25	Approved	[19]
Domperidone	DMBDPY0	Gastrointestinal disease	DE2Z	Approved	[20]
Levodopa	DMN3E57	Parkinson disease	8A00.0	Approved	[21]
Quetiapine	DM1N62C	Anorexia nervosa cachexia	6B80	Approved	[22]
Pimozide	DMW83TP	Schizophrenia	6A20	Approved	[23]
Chlorpromazine	DMBGZI3	Acute intermittent hepatic porphyria	5C58.11	Approved	[24]
Iloperidone	DM6AUFY	Schizophrenia	6A20	Approved	[25]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Dopamine D2 receptor (D2R)	TTEX248	DRD2_HUMAN	Inhibitor	[1]
Dopamine D3 receptor (D3R)	TT4C8EA	DRD3_HUMAN	Inhibitor	[1]
Dopamine D4 receptor (D4R)	TTE0A2F	DRD4_HUMAN	Inhibitor	[1]

References

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• [2] Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [4] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031127)
• [5] Pharmacology of pramipexole, a dopamine D3-preferring agonist useful in treating Parkinson's disease. Clin Neuropharmacol. 1998 May-Jun;21(3):141-51.
• [6] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [7] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [8] Safety, Pharmacokinetics, and Pharmacodynamics of Trazpiroben (TAK-906), a Novel Selective D 2 /D 3 Receptor Antagonist: A Phase 1 Randomized, Placebo-Controlled Single- and Multiple-Dose Escalation Study in Healthy Participants. Clin Pharmacol Drug Dev. 2021 Jan 18.
• [9] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [10] Dopamine/serotonin receptor ligands. 9. Oxygen-containing midsized heterocyclic ring systems and nonrigidized analogues. A step toward dopamine D5 ... J Med Chem. 2004 Aug 12;47(17):4155-8.
• [11] Dopamine D4 receptor involvement in the discriminative stimulus effects in rats of LSD, but not the phenethylamine hallucinogen DOI. Psychopharmacology (Berl). 2009 Apr;203(2):265-77.
• [12] The pipeline and future of drug development in schizophrenia. Mol Psychiatry. 2007 Oct;12(10):904-22.
• [13] Activation of dopamine D4 receptors by ABT-724 induces penile erection in rats. Proc Natl Acad Sci U S A. 2004 April 27; 101(17): 6758-6763.
• [14] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800014237)
• [15] I. NGD 94-1: identification of a novel, high-affinity antagonist at the human dopamine D4 receptor. J Pharmacol Exp Ther. 1997 Aug;282(2):1011-9.
• [16] 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.
• [17] Dopaminergic synapses in the matrix of the ventrolateral striatum after chronic haloperidol treatment. Synapse. 2002 Aug;45(2):78-85.
• [18] CYP2D6 and DRD2 genes differentially impact pharmacodynamic sensitivity and time course of prolactin response to perphenazine. Pharmacogenet Genomics. 2007 Nov;17(11):989-93.
• [19] 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.
• [20] Screening of domperidone in wastewater by high performance liquid chromatography and solid phase extraction methods. Talanta. 2006 Jan 15;68(3):928-31.
• [21] 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).
• [22] Receptor reserve-dependent properties of antipsychotics at human dopamine D2 receptors. Eur J Pharmacol. 2009 Apr 1;607(1-3):35-40.
• [23] [The benzamides tiapride, sulpiride, and amisulpride in treatment for Tourette's syndrome]. Nervenarzt. 2007 Mar;78(3):264, 266-8, 270-1.
• [24] 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.
• [25] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.