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

General Information of Drug (ID: DM2TP4Q)

• Drug Name: PG-01037 Drug Info
• Synonyms: PG-01037; PG01037; CHEMBL180010; PG 01037; GTPL6675; ZMYOIZHRXABMFZ-ONEGZZNKSA-N; BDBM50161214; ZINC52619107; NCGC00370952-01; L023518; N-[(E)-4-[4-(2,3-dichlorophenyl)piperazin-1-yl]but-2-enyl]-4-pyridin-2-ylbenzamide; N-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)but-2-enyl)-4-(pyridin-2-yl)benzamide; N-{4-[4-(2,3-Dichloro-phenyl)-piperazin-1-yl]-but-2-enyl}-4-pyridin-2-yl-benzamide

Indication

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

• Cross-matching ID:
  PubChem CID: 11477180
  TTD Drug ID: DM2TP4Q

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	[3]
Pramipexole	DMNMW9R	Parkinson disease	8A00.0	Approved	[4]
Ropinirole	DMA6S1D	Parkinson disease	8A00.0	Approved	[4]
CM-2395	DMASPWR	Schizophrenia	6A20	Phase 3	[5]
P2B-001	DM9PVHX	Parkinson disease	8A00.0	Phase 3	[6]
RP5063	DMKUE8O	Schizophrenia	6A20	Phase 2	[7]
ONC201	DMM5SCF	Endometrial cancer	2C76	Phase 2	[8]
TAK-906	DMBQD9H	Diabetic gastroparesis	DA41.00	Phase 2	[9]
GSK598809	DMGU05N	Drug abuse	6C4G.1Z	Phase 2	[10]
GSK618334	DMJPXZ4	Drug abuse	6C4G.1Z	Phase 1	[10]

Drug(s) Targeting Dopamine D4 receptor (D4R)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Clozapine	DMFC71L	Schizophrenia	6A20	Approved	[4]
Phenyltoloxamine	DMKAEQW	Allergy	4A80-4A85	Approved	[11]
CM-2395	DMASPWR	Schizophrenia	6A20	Phase 3	[5]
RP5063	DMKUE8O	Schizophrenia	6A20	Phase 2	[7]
L-745,870	DMTGR25	Psychotic disorder	6A20-6A25	Phase 2	[12]
NGD 94-1	DMM1Y8F	Schizophrenia	6A20	Phase 1	[13]
ABT-724	DMDQVY4	Erectile dysfunction	HA01.1	Discontinued in Phase 2	[14]
Lu-35138	DMQ7A35	Psychotic disorder	6A20-6A25	Discontinued in Phase 2	[15]
NGD-94-4	DMZ9WLO	Schizophrenia	6A20	Discontinued in Phase 1	[16]
PD-165167	DMD0GB4	Schizophrenia	6A20	Preclinical	[13]

Drug(s) Targeting 5-HT 2A receptor (HTR2A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Metergolin	DMJFP6G	Hyperprolactinaemia	5A60.1	Approved	[17]
ZOTEPINE	DMF3VXA	Anxiety disorder	6B00-6B0Z	Approved	[18]
Iloperidone	DM6AUFY	Schizophrenia	6A20	Approved	[19]
Flibanserin	DM70DTN	Depression	6A70-6A7Z	Approved	[3]
Lurasidone hydrochloride	DMCVPXO	Schizophrenia	6A20	Approved	[20]
Aniracetam	DMOIFW0	Cerebrovascular ischaemia	8B1Z	Approved	[21]
lumateperone tosylate	DMQ8HOJ	Schizophrenia	6A20	Approved	[22]
Sarpogrelate	DMGLP6S	Diabetic complication	5A2Y	Approved	[23]
Pimavanserin	DMR7IVC	Parkinson disease	8A00.0	Approved	[24]
Zicronapine	DMP8ESD	Schizophrenia	6A20	Phase 3	[25]

Drug(s) Targeting Dopamine D2 receptor (D2R)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dopamine	DMPGUCF	Acromegaly	5A60.0	Approved	[26]
Haloperidol	DM96SE0	Delirium		Approved	[27]
Perphenazine	DMA4MRX	Schizophrenia	6A20	Approved	[28]
Perazine	DM2AOTZ	Psychotic disorder	6A20-6A25	Approved	[29]
Domperidone	DMBDPY0	Gastrointestinal disease	DE2Z	Approved	[30]
Levodopa	DMN3E57	Parkinson disease	8A00.0	Approved	[31]
Quetiapine	DM1N62C	Anorexia nervosa cachexia	6B80	Approved	[32]
Pimozide	DMW83TP	Schizophrenia	6A20	Approved	[33]
Chlorpromazine	DMBGZI3	Acute intermittent hepatic porphyria	5C58.11	Approved	[34]
Iloperidone	DM6AUFY	Schizophrenia	6A20	Approved	[19]

Drug(s) Targeting 5-HT 1A receptor (HTR1A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Trazodone	DMK1GBJ	Depression	6A70-6A7Z	Approved	[4]
Buspirone	DMBS632	Anxiety disorder	6B00-6B0Z	Approved	[35]
OPC-34712	DMHG57U	Major depressive disorder	6A70.3	Approved	[36]
Vilazodone	DM4LECQ	Major depressive disorder	6A70.3	Approved	[37]
Flibanserin	DM70DTN	Depression	6A70-6A7Z	Approved	[3]
Gepirone	DMGX5Q0	Major depressive disorder	6A70.3	Approved	[38]
TERTATOLOL	DM2L3D5	Hypertension	BA00-BA04	Approved	[39]
Urapidil	DMD59GI	Hypertension	BA00-BA04	Approved	[40]
Treximet	DMU54QB	Migraine	8A80	Approved	[10]
CM-2395	DMASPWR	Schizophrenia	6A20	Phase 3	[5]

Drug(s) Targeting 5-HT 2C receptor (HTR2C)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Metergolin	DMJFP6G	Hyperprolactinaemia	5A60.1	Approved	[17]
Lorcaserin	DMG6OYJ	Obesity	5B81	Approved	[41]
Tramadol	DMRQD04	Osteoarthritis	FA00-FA05	Approved	[42]
Mirtazapine	DML53ZJ	Depression	6A70-6A7Z	Approved	[43]
Nefazodone	DM4ZS8M	Major depressive disorder	6A70.3	Approved	[44]
Methysergide	DM1EF73	Migraine	8A80	Approved	[45]
Eltoprazine	DMW6C81	Attention deficit hyperactivity disorder	6A05.Z	Phase 3	[46]
M100907	DM7ZFBA	Sleep-wake disorder	7A00-7B2Z	Phase 3	[47]
SR46349B	DM1ODMR	Primary insomnia	7A00	Phase 3	[48]
Vabicaserin	DM9GZW6	Psychotic disorder	6A20-6A25	Phase 2	[49]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
5-HT 1A receptor (HTR1A)	TTSQIFT	5HT1A_HUMAN	Inhibitor	[2]
5-HT 2A receptor (HTR2A)	TTJQOD7	5HT2A_HUMAN	Inhibitor	[2]
5-HT 2C receptor (HTR2C)	TTWJBZ5	5HT2C_HUMAN	Inhibitor	[2]
Dopamine D2 receptor (D2R)	TTEX248	DRD2_HUMAN	Inhibitor	[2]
Dopamine D3 receptor (D3R)	TT4C8EA	DRD3_HUMAN	Inhibitor	[2]
Dopamine D4 receptor (D4R)	TTE0A2F	DRD4_HUMAN	Inhibitor	[2]

References

• [1] 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: 6675).
• [2] Heterocyclic analogues of N-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butyl)arylcarboxamides with functionalized linking chains as novel dopamine D3... J Med Chem. 2007 Aug 23;50(17):4135-46.
• [3] Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [5] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031127)
• [6] Pharmacology of pramipexole, a dopamine D3-preferring agonist useful in treating Parkinson's disease. Clin Neuropharmacol. 1998 May-Jun;21(3):141-51.
• [7] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [8] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [9] 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.
• [10] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [11] 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.
• [12] 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.
• [13] The pipeline and future of drug development in schizophrenia. Mol Psychiatry. 2007 Oct;12(10):904-22.
• [14] 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.
• [15] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800014237)
• [16] 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.
• [17] Pharmacological characterisation of the agonist radioligand binding site of 5-HT(2A), 5-HT(2B) and 5-HT(2C) receptors. Naunyn Schmiedebergs Arch Pharmacol. 2004 Aug;370(2):114-23.
• [18] Current and novel approaches to the drug treatment of schizophrenia. J Med Chem. 2001 Feb 15;44(4):477-501.
• [19] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [20] Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
• [21] Anxiolytic effects of aniracetam in three different mouse models of anxiety and the underlying mechanism. Eur J Pharmacol. 2001 May 18;420(1):33-43.
• [22] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [23] Beneficial effects of sarpogrelate hydrochloride, a 5-HT2A receptor antagonist, supplemented with pioglitazone on diabetic model mice. Endocr Res. 2009;34(1-2):18-30.
• [24] Pimavanserin, a selective serotonin (5-HT)2A-inverse agonist, enhances the efficacy and safety of risperidone, 2mg/day, but does not enhance efficacy of haloperidol, 2mg/day: comparison with reference dose risperidone, 6mg/day.Schizophr Res.2012 Nov;141(2-3):144-52.
• [25] Clinical pipeline report, company report or official report of Lundbeck.
• [26] 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.
• [27] Dopaminergic synapses in the matrix of the ventrolateral striatum after chronic haloperidol treatment. Synapse. 2002 Aug;45(2):78-85.
• [28] CYP2D6 and DRD2 genes differentially impact pharmacodynamic sensitivity and time course of prolactin response to perphenazine. Pharmacogenet Genomics. 2007 Nov;17(11):989-93.
• [29] 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.
• [30] Screening of domperidone in wastewater by high performance liquid chromatography and solid phase extraction methods. Talanta. 2006 Jan 15;68(3):928-31.
• [31] 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).
• [32] Receptor reserve-dependent properties of antipsychotics at human dopamine D2 receptors. Eur J Pharmacol. 2009 Apr 1;607(1-3):35-40.
• [33] [The benzamides tiapride, sulpiride, and amisulpride in treatment for Tourette's syndrome]. Nervenarzt. 2007 Mar;78(3):264, 266-8, 270-1.
• [34] 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.
• [35] Interactions between corticotropin-releasing hormone and serotonin: implications for the aetiology and treatment of anxiety disorders. Handb Exp Pharmacol. 2005;(169):181-204.
• [36] Effects of brexpiprazole, a novel serotonin-dopamine activity modulator, on phencyclidine-induced cognitive deficits in mice: a role for serotonin 5-HT1A receptors.Pharmacol Biochem Behav.2014 Sep;124:245-9.
• [37] 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
• [38] Novel drugs and therapeutic targets for severe mood disorders. Neuropsychopharmacology. 2008 Aug;33(9):2080-92.
• [39] Synthesis of new derivatives of 8-OH-DPAT: Influence of substitution on the aromatic ring on the pharmacological profile, Bioorg. Med. Chem. Lett. 3(10):2035-2038 (1993).
• [40] Urapidil. A reappraisal of its use in the management of hypertension. Drugs. 1998 Nov;56(5):929-55.
• [41] Anti-obesity drugs. Expert Opin Pharmacother. 2008 Jun;9(8):1339-50.
• [42] The inhibitory effects of tramadol on 5-hydroxytryptamine type 2C receptors expressed in Xenopus oocytes. Anesth Analg. 2004 May;98(5):1401-6, table of contents.
• [43] Inverse agonist and neutral antagonist actions of antidepressants at recombinant and native 5-hydroxytryptamine2C receptors: differential modulatio... Mol Pharmacol. 2008 Mar;73(3):748-57.
• [44] Serotonin 5-HT2C receptors as a target for the treatment of depressive and anxious states: focus on novel therapeutic strategies. Therapie. 2005 Sep-Oct;60(5):441-60.
• [45] Spinal serotonin receptor activation modulates the exercise ventilatory response with increased dead space in goats. Respir Physiol Neurobiol. 2008 May 31;161(3):230-8.
• [46] Clinical pipeline report, company report or official report of Jazz Pharmaceuticals.
• [47] Non-basic ligands for aminergic GPCRs: the discovery and development diaryl sulfones as selective, orally bioavailable 5-HT2A receptor antagonists ... Bioorg Med Chem Lett. 2010 Jun 15;20(12):3708-12.
• [48] SR46349-B, a 5-HT(2A/2C) receptor antagonist, potentiates haloperidol-induced dopamine release in rat medial prefrontal cortex and nucleus accumbens. Neuropsychopharmacology. 2002 Sep;27(3):430-41.
• [49] Prediction of Efficacy of Vabicaserin, a 5-HT2C Agonist, for the Treatment of Schizophrenia Using a Quantitative Systems Pharmacology Model.CPT Pharmacometrics Syst Pharmacol.2014 Apr 23;3:e111.