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

General Information of Drug (ID: DM79KLR)

• Drug Name: nafadotride Drug Info
• Synonyms: Nafadotride; 149649-22-9; (+-)-nafadotride; N-[(1-BUTYL-2-PYRROLIDINYL)METHYL]-4-CYANO-1-METHOXY-2-NAPHTHALENECARBOXAMIDE; N-[(1-butylpyrrolidin-2-yl)methyl]-4-cyano-1-methoxynaphthalene-2-carboxamide; CHEMBL286252; CHEBI:64191; A1-01951; SMR000466292; AC1MPBUT; GTPL44; MLS000758952; MLS001424218; SCHEMBL635866; DTXSID1042603; CTK8H0240; MolPort-023-276-076; HMS3394A15; HMS3267P15; HMS2232B11; HMS2052A15; HMS3370D02; BCP27779; BDBM50133923; AKOS024257976; TRA0072321; CCG-101119; NC00369; SAM001247092; CPD000466292; LS-186981; LS-187623

Indication

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

• Cross-matching ID:
  PubChem CID: 3408722
  ChEBI ID: CHEBI:64191
  CAS Number: CAS 149649-22-9
  TTD Drug ID: DM79KLR

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	[5]
Pramipexole	DMNMW9R	Parkinson disease	8A00.0	Approved	[6]
Ropinirole	DMA6S1D	Parkinson disease	8A00.0	Approved	[6]
CM-2395	DMASPWR	Schizophrenia	6A20	Phase 3	[7]
P2B-001	DM9PVHX	Parkinson disease	8A00.0	Phase 3	[8]
RP5063	DMKUE8O	Schizophrenia	6A20	Phase 2	[9]
ONC201	DMM5SCF	Endometrial cancer	2C76	Phase 2	[10]
TAK-906	DMBQD9H	Diabetic gastroparesis	DA41.00	Phase 2	[11]
GSK598809	DMGU05N	Drug abuse	6C4G.1Z	Phase 2	[12]
GSK618334	DMJPXZ4	Drug abuse	6C4G.1Z	Phase 1	[12]

Drug(s) Targeting Dopamine D4 receptor (D4R)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Clozapine	DMFC71L	Schizophrenia	6A20	Approved	[6]
Phenyltoloxamine	DMKAEQW	Allergy	4A80-4A85	Approved	[13]
CM-2395	DMASPWR	Schizophrenia	6A20	Phase 3	[7]
RP5063	DMKUE8O	Schizophrenia	6A20	Phase 2	[9]
L-745,870	DMTGR25	Psychotic disorder	6A20-6A25	Phase 2	[14]
NGD 94-1	DMM1Y8F	Schizophrenia	6A20	Phase 1	[15]
ABT-724	DMDQVY4	Erectile dysfunction	HA01.1	Discontinued in Phase 2	[16]
Lu-35138	DMQ7A35	Psychotic disorder	6A20-6A25	Discontinued in Phase 2	[17]
NGD-94-4	DMZ9WLO	Schizophrenia	6A20	Discontinued in Phase 1	[18]
PD-165167	DMD0GB4	Schizophrenia	6A20	Preclinical	[15]

Drug(s) Targeting Dopamine D2 receptor (D2R)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dopamine	DMPGUCF	Acromegaly	5A60.0	Approved	[19]
Haloperidol	DM96SE0	Delirium		Approved	[20]
Perphenazine	DMA4MRX	Schizophrenia	6A20	Approved	[21]
Perazine	DM2AOTZ	Psychotic disorder	6A20-6A25	Approved	[22]
Domperidone	DMBDPY0	Gastrointestinal disease	DE2Z	Approved	[23]
Levodopa	DMN3E57	Parkinson disease	8A00.0	Approved	[24]
Quetiapine	DM1N62C	Anorexia nervosa cachexia	6B80	Approved	[25]
Pimozide	DMW83TP	Schizophrenia	6A20	Approved	[26]
Chlorpromazine	DMBGZI3	Acute intermittent hepatic porphyria	5C58.11	Approved	[27]
Iloperidone	DM6AUFY	Schizophrenia	6A20	Approved	[28]

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Trazodone	DMK1GBJ	Depression	6A70-6A7Z	Approved	[6]
Buspirone	DMBS632	Anxiety disorder	6B00-6B0Z	Approved	[29]
OPC-34712	DMHG57U	Major depressive disorder	6A70.3	Approved	[30]
Vilazodone	DM4LECQ	Major depressive disorder	6A70.3	Approved	[31]
Flibanserin	DM70DTN	Depression	6A70-6A7Z	Approved	[5]
Gepirone	DMGX5Q0	Major depressive disorder	6A70.3	Approved	[32]
TERTATOLOL	DM2L3D5	Hypertension	BA00-BA04	Approved	[33]
Urapidil	DMD59GI	Hypertension	BA00-BA04	Approved	[34]
Treximet	DMU54QB	Migraine	8A80	Approved	[12]
CM-2395	DMASPWR	Schizophrenia	6A20	Phase 3	[7]

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	Agonist	[2]
Dopamine D2 receptor (D2R)	TTEX248	DRD2_HUMAN	Antagonist	[3]
Dopamine D3 receptor (D3R)	TT4C8EA	DRD3_HUMAN	Antagonist	[3]
Dopamine D4 receptor (D4R)	TTE0A2F	DRD4_HUMAN	Antagonist	[4]

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: 44).
• [2] Agonist and antagonist actions of antipsychotic agents at 5-HT1A receptors: a [35S]GTPgammaS binding study. Eur J Pharmacol. 1998 Aug 21;355(2-3):245-56.
• [3] Nafadotride, a potent preferential dopamine D3 receptor antagonist, activates locomotion in rodents. J Pharmacol Exp Ther. 1995 Dec;275(3):1239-46.
• [4] Nonconserved residues in the second transmembrane-spanning domain of the D(4) dopamine receptor are molecular determinants of D(4)-selective pharmacology. Mol Pharmacol. 2000 Jan;57(1):144-52.
• [5] Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
• [6] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [7] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031127)
• [8] Pharmacology of pramipexole, a dopamine D3-preferring agonist useful in treating Parkinson's disease. Clin Neuropharmacol. 1998 May-Jun;21(3):141-51.
• [9] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [10] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [11] 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.
• [12] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [13] 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.
• [14] 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.
• [15] The pipeline and future of drug development in schizophrenia. Mol Psychiatry. 2007 Oct;12(10):904-22.
• [16] 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.
• [17] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800014237)
• [18] 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.
• [19] 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.
• [20] Dopaminergic synapses in the matrix of the ventrolateral striatum after chronic haloperidol treatment. Synapse. 2002 Aug;45(2):78-85.
• [21] CYP2D6 and DRD2 genes differentially impact pharmacodynamic sensitivity and time course of prolactin response to perphenazine. Pharmacogenet Genomics. 2007 Nov;17(11):989-93.
• [22] 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.
• [23] Screening of domperidone in wastewater by high performance liquid chromatography and solid phase extraction methods. Talanta. 2006 Jan 15;68(3):928-31.
• [24] 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).
• [25] Receptor reserve-dependent properties of antipsychotics at human dopamine D2 receptors. Eur J Pharmacol. 2009 Apr 1;607(1-3):35-40.
• [26] [The benzamides tiapride, sulpiride, and amisulpride in treatment for Tourette's syndrome]. Nervenarzt. 2007 Mar;78(3):264, 266-8, 270-1.
• [27] 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.
• [28] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [29] Interactions between corticotropin-releasing hormone and serotonin: implications for the aetiology and treatment of anxiety disorders. Handb Exp Pharmacol. 2005;(169):181-204.
• [30] 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.
• [31] 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
• [32] Novel drugs and therapeutic targets for severe mood disorders. Neuropsychopharmacology. 2008 Aug;33(9):2080-92.
• [33] 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).
• [34] Urapidil. A reappraisal of its use in the management of hypertension. Drugs. 1998 Nov;56(5):929-55.