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

General Information of Drug (ID: DM6M9GC)

• Drug Name: ZD-3638 Drug Info
• Synonyms: ZD-3638; SCHEMBL1152094; CHEMBL264026

Indication

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

• Cross-matching ID:
  PubChem CID: 9955820
  TTD Drug ID: DM6M9GC

Molecule-Related Drug Atlas

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Metergolin	DMJFP6G	Hyperprolactinaemia	5A60.1	Approved	[2]
ZOTEPINE	DMF3VXA	Anxiety disorder	6B00-6B0Z	Approved	[3]
Iloperidone	DM6AUFY	Schizophrenia	6A20	Approved	[4]
Flibanserin	DM70DTN	Depression	6A70-6A7Z	Approved	[5]
Lurasidone hydrochloride	DMCVPXO	Schizophrenia	6A20	Approved	[6]
Aniracetam	DMOIFW0	Cerebrovascular ischaemia	8B1Z	Approved	[7]
lumateperone tosylate	DMQ8HOJ	Schizophrenia	6A20	Approved	[8]
Sarpogrelate	DMGLP6S	Diabetic complication	5A2Y	Approved	[9]
Pimavanserin	DMR7IVC	Parkinson disease	8A00.0	Approved	[10]
Zicronapine	DMP8ESD	Schizophrenia	6A20	Phase 3	[11]

Drug(s) Targeting Dopamine D5 receptor (D5R)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Phenyltoloxamine	DMKAEQW	Allergy	4A80-4A85	Approved	[12]
LE-300	DMGJL16	Schizophrenia	6A20	Preclinical	[1]
GMC-283	DMT1RH6	Schizophrenia	6A20	Terminated	[1]
(+/-)-nantenine	DM0L3GE	Discovery agent	N.A.	Investigative	[13]
ISOCLOZAPINE	DM52CPU	Discovery agent	N.A.	Investigative	[14]
FLUMEZAPINE	DMW0HOG	Discovery agent	N.A.	Investigative	[15]
ISOLOXAPINE	DMH1BN4	Discovery agent	N.A.	Investigative	[16]
1-Dibenzo[b,f]oxepin-10-yl-4-methyl-piperazine	DMOL2Y0	Discovery agent	N.A.	Investigative	[14]
1-[3-(2-Benzyl-phenoxy)-propyl]-pyrrolidine	DMD2NXL	Discovery agent	N.A.	Investigative	[12]
STEPHOLIDINE	DMGMXQC	Discovery agent	N.A.	Investigative	[17]

Drug(s) Targeting Dopamine D2 receptor (D2R)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dopamine	DMPGUCF	Acromegaly	5A60.0	Approved	[18]
Haloperidol	DM96SE0	Delirium		Approved	[19]
Perphenazine	DMA4MRX	Schizophrenia	6A20	Approved	[20]
Perazine	DM2AOTZ	Psychotic disorder	6A20-6A25	Approved	[21]
Domperidone	DMBDPY0	Gastrointestinal disease	DE2Z	Approved	[22]
Levodopa	DMN3E57	Parkinson disease	8A00.0	Approved	[23]
Quetiapine	DM1N62C	Anorexia nervosa cachexia	6B80	Approved	[24]
Pimozide	DMW83TP	Schizophrenia	6A20	Approved	[25]
Chlorpromazine	DMBGZI3	Acute intermittent hepatic porphyria	5C58.11	Approved	[26]
Iloperidone	DM6AUFY	Schizophrenia	6A20	Approved	[4]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
5-HT 2A receptor (HTR2A)	TTJQOD7	5HT2A_HUMAN	Binder	[1]
Dopamine D2 receptor (D2R)	TTEX248	DRD2_HUMAN	Binder	[1]
Dopamine D5 receptor (D5R)	TTS2PH3	DRD5_HUMAN	Binder	[1]

References

• [1] The pipeline and future of drug development in schizophrenia. Mol Psychiatry. 2007 Oct;12(10):904-22.
• [2] 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.
• [3] Current and novel approaches to the drug treatment of schizophrenia. J Med Chem. 2001 Feb 15;44(4):477-501.
• [4] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [5] Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
• [6] Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
• [7] 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.
• [8] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [9] 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.
• [10] 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.
• [11] Clinical pipeline report, company report or official report of Lundbeck.
• [12] 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.
• [13] Synthetic studies and pharmacological evaluations on the MDMA ('Ecstasy') antagonist nantenine. Bioorg Med Chem Lett. 2010 Jan 15;20(2):628-31.
• [14] Affinity of 10-(4-methylpiperazino)dibenz[b,f]oxepins for clozapine and spiroperidol binding sites in rat brain. J Med Chem. 1982 Jul;25(7):855-8.
• [15] Effects of conformationally restricted 4-piperazinyl-10H-thienobenzodiazepine neuroleptics on central dopaminergic and cholinergic systems. J Med Chem. 1982 Oct;25(10):1133-40.
• [16] Synthesis of clozapine analogues and their affinity for clozapine and spiroperidol binding sites in rat brain. J Med Chem. 1981 Sep;24(9):1021-6.
• [17] Dibenzazecine scaffold rebuilding--is the flexibility always essential for high dopamine receptor affinities Bioorg Med Chem. 2009 Oct 1;17(19):6898-907.
• [18] 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.
• [19] Dopaminergic synapses in the matrix of the ventrolateral striatum after chronic haloperidol treatment. Synapse. 2002 Aug;45(2):78-85.
• [20] CYP2D6 and DRD2 genes differentially impact pharmacodynamic sensitivity and time course of prolactin response to perphenazine. Pharmacogenet Genomics. 2007 Nov;17(11):989-93.
• [21] 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.
• [22] Screening of domperidone in wastewater by high performance liquid chromatography and solid phase extraction methods. Talanta. 2006 Jan 15;68(3):928-31.
• [23] 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).
• [24] Receptor reserve-dependent properties of antipsychotics at human dopamine D2 receptors. Eur J Pharmacol. 2009 Apr 1;607(1-3):35-40.
• [25] [The benzamides tiapride, sulpiride, and amisulpride in treatment for Tourette's syndrome]. Nervenarzt. 2007 Mar;78(3):264, 266-8, 270-1.
• [26] 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.