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

General Information of Drug (ID: DMMVB5P)

• Drug Name: BOLDINE Drug Info
• Synonyms: Boldine; 476-70-0; Uniboldina; Boldin; (S)-Boldine; Boldine chloroform; (+)-Boldine; NSC 65689; UNII-8I91GE2769; (S)-(+)-Boldine; EINECS 207-509-9; BRN 0094036; 1,10-Dimethoxy-2,9-dihydroxyaporphine; CHEMBL388342; CHEBI:3148; 1,10-Dimethoxy-6a-alpha-aporphine-2,9-diol; LZJRNLRASBVRRX-ZDUSSCGKSA-N; 8I91GE2769; 4H-Dibenzo(de,g)quinoline-2,9-diol, 5,6,6a,7-tetrahydro-1,10-dimethoxy-6-methyl-, (S)-; 4H-Dibenzo(de,g)quinoline-2,9-diol, 5,6,6a,7-tetrahydro-1,10-dimethoxy-6-methyl-, (6aS)-

Indication

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

• Cross-matching ID:
  PubChem CID: 10154
  ChEBI ID: CHEBI:3148
  CAS Number: CAS 476-70-0
  TTD Drug ID: DMMVB5P

Molecule-Related Drug Atlas

Drug(s) Targeting Dopamine D1 receptor (D1R)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Phenyltoloxamine	DMKAEQW	Allergy	4A80-4A85	Approved	[4]
Pergolide	DM14MAE	Parkinson disease	8A00.0	Approved	[5]
Methylergonovine	DMBEX4O	Spontaneous abortion	JA00.0	Approved	[6]
Fenoldopam	DMFAOKP	Hypertension	BA00-BA04	Approved	[7]
Zicronapine	DMP8ESD	Schizophrenia	6A20	Phase 3	[8]
Ecopipam	DMS9R43	Cocaine addiction	6C45.2	Phase 3	[9]
DAS-431	DMM3BPL	Dementia	6D80-6D86	Phase 2	[10]
Dihydrexidine	DMACPQO	Psychotic disorder	6A20-6A25	Phase 1/2	[11]
Lu AF28996	DMY572G	Parkinson disease	8A00.0	Phase 1	[12]
BAM-1110	DMPMKUF	Parkinson disease	8A00.0	Discontinued in Phase 2	[13]

Drug(s) Targeting Dopamine D2 receptor (D2R)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dopamine	DMPGUCF	Acromegaly	5A60.0	Approved	[14]
Haloperidol	DM96SE0	Delirium		Approved	[15]
Perphenazine	DMA4MRX	Schizophrenia	6A20	Approved	[16]
Perazine	DM2AOTZ	Psychotic disorder	6A20-6A25	Approved	[17]
Domperidone	DMBDPY0	Gastrointestinal disease	DE2Z	Approved	[18]
Levodopa	DMN3E57	Parkinson disease	8A00.0	Approved	[19]
Quetiapine	DM1N62C	Anorexia nervosa cachexia	6B80	Approved	[20]
Pimozide	DMW83TP	Schizophrenia	6A20	Approved	[21]
Chlorpromazine	DMBGZI3	Acute intermittent hepatic porphyria	5C58.11	Approved	[22]
Iloperidone	DM6AUFY	Schizophrenia	6A20	Approved	[23]

Drug(s) Targeting Neuronal acetylcholine receptor alpha-4 (CHRNA4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Trimethaphan	DMHF4IQ	Aneurysm	BD51.Z	Approved	[24]
Pentolinium	DM38VYQ	Hypotension	BA20-BA21	Approved	[25]
CYTISINE	DMUF0BJ	Tobacco dependence	6C4A.2	Phase 3	[26]
ABT-594	DMGMBCW	N. A.	N. A.	Discontinued in Phase 2	[27]
ABT-418	DMNP72I	Alzheimer disease	8A20	Discontinued in Phase 2	[28]
HOMOEPIBATIDINE	DMHP9WV	N. A.	N. A.	Terminated	[26]
4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one	DMM9X0G	Discovery agent	N.A.	Investigative	[29]
Barbituric acid derivative	DM2I19P	Discovery agent	N.A.	Investigative	[30]
(2S,3S)-2-Phenyl-3,5,5-trimethylmorpholin-2-ol	DMDUGZS	Discovery agent	N.A.	Investigative	[31]
(2S,3S)-2-(m-Tolyl)-3,5,5-trimethylmorpholin-2-ol	DMDUI8R	Discovery agent	N.A.	Investigative	[31]

Drug(s) Targeting Neuronal acetylcholine receptor beta-2 (CHRNB2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CYTISINE	DMUF0BJ	Tobacco dependence	6C4A.2	Phase 3	[26]
TC-5214	DM8AM60	Palmar hyperhidrosis	EE00.00	Phase 2	[32]
SUVN-911	DMLPBVF	Major depressive disorder	6A70.3	Phase 1	[33]
AZD-9684	DMHA5ME	Thrombosis	DB61-GB90	Discontinued in Phase 2	[34]
ABT-594	DMGMBCW	N. A.	N. A.	Discontinued in Phase 2	[27]
ABT-418	DMNP72I	Alzheimer disease	8A20	Discontinued in Phase 2	[35]
HOMOEPIBATIDINE	DMHP9WV	N. A.	N. A.	Terminated	[26]
4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one	DMM9X0G	Discovery agent	N.A.	Investigative	[29]
(2S,3S)-2-Phenyl-3,5,5-trimethylmorpholin-2-ol	DMDUGZS	Discovery agent	N.A.	Investigative	[31]
(2S,3S)-2-(m-Tolyl)-3,5,5-trimethylmorpholin-2-ol	DMDUI8R	Discovery agent	N.A.	Investigative	[31]

Drug(s) Affected By Telomerase reverse transcriptase (TERT)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[36]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[37]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[38]
Selenium	DM25CGV	N. A.	N. A.	Approved	[39]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[40]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[41]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[42]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[43]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[44]
Aspirin	DM672AH	Acute coronary syndrome	BA41	Approved	[45]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Dopamine D1 receptor (D1R)	TTZFYLI	DRD1_HUMAN	Inhibitor	[2]
Dopamine D2 receptor (D2R)	TTEX248	DRD2_HUMAN	Inhibitor	[2]
Neuronal acetylcholine receptor alpha-4 (CHRNA4)	TT4H1MQ	ACHA4_HUMAN	Inhibitor	[1]
Neuronal acetylcholine receptor beta-2 (CHRNB2)	TT5KPZR	ACHB2_HUMAN	Inhibitor	[1]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Telomerase reverse transcriptase (TERT)	OT085VVA	TERT_HUMAN	Gene/Protein Processing	[3]

References

• [1] Aporphine metho salts as neuronal nicotinic acetylcholine receptor blockers. Bioorg Med Chem. 2007 May 15;15(10):3368-72.
• [2] Halogenated boldine derivatives with enhanced monoamine receptor selectivity. J Nat Prod. 2000 Apr;63(4):480-4.
• [3] Boldine, a natural aporphine alkaloid, inhibits telomerase at non-toxic concentrations. Chem Biol Interact. 2015 Apr 25;231:27-34. doi: 10.1016/j.cbi.2015.02.020. Epub 2015 Mar 3.
• [4] 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.
• [5] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [6] Reinforcement in an in vitro analog of appetitive classical conditioning of feeding behavior in Aplysia: blockade by a dopamine antagonist. Learn Mem. 2005 May-Jun;12(3):216-20.
• [7] Etiology of iodinated radiocontrast nephrotoxicity and its attenuation by beraprost. Yakugaku Zasshi. 2008 Jul;128(7):1023-9.
• [8] Clinical pipeline report, company report or official report of Lundbeck.
• [9] A D1 receptor antagonist, ecopipam, for treatment of tics in Tourette syndrome.Clin Neuropharmacol.2014 Jan-Feb;37(1):26-30.
• [10] Adrogolide HCl (ABT-431; DAS-431), a prodrug of the dopamine D1 receptor agonist, A-86929: preclinical pharmacology and clinical data. CNS Drug Rev. 2001 Fall;7(3):305-16.
• [11] trans-2,3-dihydroxy-6a,7,8,12b-tetrahydro-6H-chromeno[3,4-c]isoquinoline: synthesis, resolution, and preliminary pharmacological characterization o... J Med Chem. 2006 Nov 16;49(23):6848-57.
• [12] Clinical pipeline report, company report or official report of Lundbeck
• [13] Therapeutic effects of dopamine D1/D2 receptor agonists on detrusor hyperreflexia in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned parkinso... J Pharmacol Exp Ther. 1998 Jul;286(1):228-33.
• [14] 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.
• [15] Dopaminergic synapses in the matrix of the ventrolateral striatum after chronic haloperidol treatment. Synapse. 2002 Aug;45(2):78-85.
• [16] CYP2D6 and DRD2 genes differentially impact pharmacodynamic sensitivity and time course of prolactin response to perphenazine. Pharmacogenet Genomics. 2007 Nov;17(11):989-93.
• [17] 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.
• [18] Screening of domperidone in wastewater by high performance liquid chromatography and solid phase extraction methods. Talanta. 2006 Jan 15;68(3):928-31.
• [19] 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).
• [20] Receptor reserve-dependent properties of antipsychotics at human dopamine D2 receptors. Eur J Pharmacol. 2009 Apr 1;607(1-3):35-40.
• [21] [The benzamides tiapride, sulpiride, and amisulpride in treatment for Tourette's syndrome]. Nervenarzt. 2007 Mar;78(3):264, 266-8, 270-1.
• [22] 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.
• [23] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [24] Mechanism of long-lasting block of ganglion nicotinic receptors by mono-ammonium compounds with long aliphatic chain. J Auton Nerv Syst. 1994 Aug;48(3):231-40.
• [25] Nicotinic and nonnicotinic receptor-mediated actions of vinblastine. Proc Soc Exp Biol Med. 1993 Jul;203(3):372-6.
• [26] Epibatidine isomers and analogues: structure-activity relationships. Bioorg Med Chem Lett. 2006 Nov 1;16(21):5493-7.
• [27] The nicotinic acetylcholine receptor agonist ABT-594 increases FGF-2 expression in various rat brain regions. Neuroreport. 1999 Dec 16;10(18):3909-13.
• [28] (S)-3-methyl-5-(1-methyl-2-pyrrolidinyl)isoxazole (ABT 418): a novel cholinergic ligand with cognition-enhancing and anxiolytic activities: II. In vivo characterization. J Pharmacol Exp Ther. 1994 Jul;270(1):319-28.
• [29] Discovery of N-{1-[3-(3-oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl]piperidin-4-yl}-2-phenylacetamide (Lu AE51090): an allosteric muscarinic M1 rec... J Med Chem. 2010 Sep 9;53(17):6386-97.
• [30] Whiting PJ: The GABAA receptor gene family: new opportunities for drug development. Curr Opin Drug Discov Devel. 2003 Sep;6(5):648-57.
• [31] Synthesis and characterization of in vitro and in vivo profiles of hydroxybupropion analogues: aids to smoking cessation. J Med Chem. 2010 Jun 24;53(12):4731-48.
• [32] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [33] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [34] Blockade and activation of the human neuronal nicotinic acetylcholine receptors by atracurium and laudanosine. Anesthesiology. 2001 Apr;94(4):643-51.
• [35] Nicotine, brain nicotinic receptors, and neuropsychiatric disorders. Arch Med Res. 2000 Mar-Apr;31(2):131-44.
• [36] Effect of ellagic acid on the expression of human telomerase reverse transcriptase (hTERT) alpha+beta+ transcript in estrogen receptor-positive MCF-7 breast cancer cells. Clin Biochem. 2009 Sep;42(13-14):1358-62. doi: 10.1016/j.clinbiochem.2009.05.017. Epub 2009 Jun 6.
• [37] Antiproliferative effects of gefitinib are associated with suppression of E2F-1 expression and telomerase activity. Anticancer Res. 2006 Sep-Oct;26(5A):3387-91.
• [38] Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
• [39] Inhibitory effects of selenium on telomerase activity and hTERT expression in cadmium-transformed 16HBE cells. Biomed Environ Sci. 2007 Aug;20(4):307-12.
• [40] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [41] Troglitazone suppresses telomerase activity independently of PPARgamma in estrogen-receptor negative breast cancer cells. BMC Cancer. 2010 Jul 22;10:390. doi: 10.1186/1471-2407-10-390.
• [42] Analysis of telomerase activity and RNA expression in a patient with acute promyelocytic leukemia treated with all-trans retinoic acid. Pediatr Blood Cancer. 2006 Apr;46(4):506-11. doi: 10.1002/pbc.20392.
• [43] Characterization of the functional and growth properties of long-term cell cultures established from a human somatostatinoma. Endocr Relat Cancer. 2006 Mar;13(1):79-93. doi: 10.1677/erc.1.00988.
• [44] Characterization of arsenic-induced cytogenetic alterations in acute promyelocytic leukemia cell line, NB4. Med Oncol. 2012 Jun;29(2):1209-16. doi: 10.1007/s12032-011-9946-4. Epub 2011 May 5.
• [45] Lunasin, a novel seed peptide, sensitizes human breast cancer MDA-MB-231 cells to aspirin-arrested cell cycle and induced apoptosis. Chem Biol Interact. 2010 Jul 30;186(2):127-34. doi: 10.1016/j.cbi.2010.04.027. Epub 2010 May 21.