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

General Information of Drug (ID: DMKYQWG)

• Drug Name: NORHARMANE Drug Info
• Synonyms: 9H-Pyrido[3,4-B]indole; Norharman; Norharmane; 244-63-3; beta-Carboline; 2,9-Diazafluorene; Carbazoline; 9H-Beta-carboline; 2-Azacarbazole; 9H-Pyrido(3,4-B)indole; .beta.-Carboline; Carbazoline (VAN); b-carboline; beta Carboline; 2H-Pyrido[3,4-b]indole; UNII-94HMA1I78O; CCRIS 6915; CHEBI:109895; EINECS 205-959-0; NSC 84417; BRN 0128414; MLS000069651; 94HMA1I78O; CHEMBL275224; AIFRHYZBTHREPW-UHFFFAOYSA-N; Norharman, 98%; SMR000058207; AK-25655; N-8720; N-8700; 244-66-6; SR-01000000213; 9h-; Prestwick_363; Norharmane, 98%; zlchem 7

Indication

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

• Cross-matching ID:
  PubChem CID: 64961
  ChEBI ID: CHEMBL275224
  CAS Number: CAS 244-63-3
  TTD Drug ID: DMKYQWG

Molecule-Related Drug Atlas

Drug(s) Targeting GABA(A) receptor alpha-1 (GABRA1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ethanol	DMDRQZU	Chronic pain	MG30	Approved	[5]
Zolpidem	DMWOSKJ	Insomnia	7A00-7A0Z	Approved	[6]
Methoxyflurane	DML0RAE	Anaesthesia	9A78.6	Approved	[5]
Nitrazepam	DMEGIQ6	Epilepsy	8A60-8A68	Approved	[5]
Allopregnanolone	DMNLHAC	Depression	6A70-6A7Z	approved	[7]
Clobazam - Lundbeck	DMW1OQ0	Anxiety disorder	6B00-6B0Z	Approved	[5]
Hexobarbital	DMQ314B	Anaesthesia	9A78.6	Approved	[5]
THIOCOLCHICOSIDE	DMEPWYA	Muscle spasm	MB47.3	Approved	[8]
Meprobamate	DMHM93Y	Anxiety		Approved	[5]
Zaleplon	DMGFWSM	Insomnia	7A00-7A0Z	Approved	[9]

Drug(s) Targeting Gamma-aminobutyric acid receptor (GAR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Phenobarbital	DMXZOCG	Cluster headache	8A81.0	Approved	[5]
Allopregnanolone	DMNLHAC	Depression	6A70-6A7Z	approved	[10]
THIOCOLCHICOSIDE	DMEPWYA	Muscle spasm	MB47.3	Approved	[8]
Clonazepam	DMTO13J	Absence epilepsy		Approved	[11]
Piperazine	DMTY9LU	Ascariasis	1F62	Approved	[12]
Alpidem	DMN7Y9K	Anxiety disorder	6B00-6B0Z	Approved	[13]
Moxidectin	DMYGHX5	Onchocerciasis	1F6A	Approved	[14]
DP-VPA	DMGOXPQ	Bipolar disorder	6A60	Approved	[15]
ANDROSTERONE	DMITJAK	N. A.	N. A.	Phase 3	[10]
ZK-93423	DMFWMKZ	Epileptic seizures	8A61-8A6Z	Phase 3	[16]

Drug(s) Affected By Solute carrier family 22 member 2 (SLC22A2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[17]
Cimetidine	DMH61ZB	Acid-reflux disorder	DA22	Approved	[18]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[18]
Ranitidine	DM0GUSX	Gastric ulcer	DA60	Approved	[19]
Lamivudine	DMI347A	Chronic HBV infection	1E51.0Z	Approved	[20]
Famotidine	DMRL3AB	Gastric ulcer	DA60	Approved	[19]
Sulindac	DM2QHZU	Acute myelogenous leukaemia	2A41	Approved	[21]
Trospium chloride	DM32XZT	Discovery agent	N.A.	Approved	[22]
Phenoxybenzamine	DM8KSQH	Malignant essential hypertension	BA00	Approved	[23]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[24]

Drug(s) Affected By Solute carrier family 22 member 1 (SLC22A1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Phenoxybenzamine	DM8KSQH	Malignant essential hypertension	BA00	Approved	[23]
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[17]
Trospium chloride	DM32XZT	Discovery agent	N.A.	Approved	[22]
Ranitidine	DM0GUSX	Gastric ulcer	DA60	Approved	[25]
Lamivudine	DMI347A	Chronic HBV infection	1E51.0Z	Approved	[20]
Sulindac	DM2QHZU	Acute myelogenous leukaemia	2A41	Approved	[21]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[26]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[27]
Rifampicin	DM5DSFZ	Non-insulin dependent diabetes	5A11	Approved	[28]
Ibuprofen	DM8VCBE	Dysmenorrhea	GA34.3	Approved	[21]

Drug(s) Affected By Solute carrier family 22 member 3 (SLC22A3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Epinephrine	DM3KJBC	Acute asthma	CA23	Approved	[29]
Ergotidine	DM78IME	Osteoarthritis	FA00-FA05	Approved	[29]
Norepinephrine	DMOUC09	Alopecia	ED70	Approved	[29]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[30]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[31]
Phenoxybenzamine	DM8KSQH	Malignant essential hypertension	BA00	Approved	[23]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[32]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[24]
Enzalutamide	DMGL19D	Prostate cancer	2C82.0	Approved	[33]
Mifepristone	DMGZQEF	Cushing disease	5A70	Approved	[34]

Drug(s) Affected By Poly polymerase 1 (PARP1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[35]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[36]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[37]
Nitric Oxide	DM1RBYG	Hypertension	BA00-BA04	Approved	[38]
Citalopram	DM2G9AE	Acute coronary syndrome	BA41	Approved	[39]
Ciprofloxacin XR	DM2NLS9	Acute gonococcal cervicitis		Approved	[40]
Imipramine	DM2NUH3	Depression	6A70-6A7Z	Approved	[39]
Colchicine	DM2POTE	Acute gout flare	FA25.0	Approved	[41]
Sulindac	DM2QHZU	Acute myelogenous leukaemia	2A41	Approved	[42]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[43]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
GABA(A) receptor alpha-1 (GABRA1)	TT1MPAY	GBRA1_HUMAN	Inhibitor	[2]
Gamma-aminobutyric acid receptor (GAR)	TTNJYV2	NOUNIPROTAC	Inhibitor	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Protein Interaction/Cellular Processes	[3]
Solute carrier family 22 member 1 (SLC22A1)	OT7817I4	S22A1_HUMAN	Gene/Protein Processing	[4]
Solute carrier family 22 member 2 (SLC22A2)	OTGFK1AL	S22A2_HUMAN	Gene/Protein Processing	[4]
Solute carrier family 22 member 3 (SLC22A3)	OTQYGVXX	S22A3_HUMAN	Gene/Protein Processing	[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: 8222).
• [2] Synthesis of novel 3-substituted beta-carbolines as benzodiazepine receptor ligands: probing the benzodiazepine receptor pharmacophore. J Med Chem. 1988 Sep;31(9):1854-61.
• [3] Heterocyclic aromatic amines induce Neuro-2a cells cytotoxicity through oxidative stress-mediated mitochondria-dependent apoptotic signals. Food Chem Toxicol. 2022 Oct;168:113376. doi: 10.1016/j.fct.2022.113376. Epub 2022 Aug 17.
• [4] Inhibition of organic cation transporter (OCT) activities by carcinogenic heterocyclic aromatic amines. Toxicol In Vitro. 2019 Feb;54:10-22. doi: 10.1016/j.tiv.2018.08.015. Epub 2018 Sep 3.
• [5] DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6.
• [6] Zolpidem, a selective GABA(A) receptor alpha1 subunit agonist, induces comparable Fos expression in oxytocinergic neurons of the hypothalamic paraventricular and accessory but not supraoptic nuclei in the rat.Brain Res Bull.2006 Dec 11;71(1-3):200-7.
• [7] Neurosteroid analogues. 10. The effect of methyl group substitution at the C-6 and C-7 positions on the GABA modulatory and anesthetic actions of (... J Med Chem. 2005 Apr 21;48(8):3051-9.
• [8] 3-demethoxy-3-glycosylaminothiocolchicines: Synthesis of a new class of putative muscle relaxant compounds. J Med Chem. 2006 Sep 7;49(18):5571-7.
• [9] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [10] Neurosteroid analogues. 11. Alternative ring system scaffolds: gamma-aminobutyric acid receptor modulation and anesthetic actions of benz[f]indenes. J Med Chem. 2006 Jul 27;49(15):4595-605.
• [11] Glutamate- and GABA-based CNS therapeutics. Curr Opin Pharmacol. 2006 Feb;6(1):7-17.
• [12] Cyclooctadepsipeptides--an anthelmintically active class of compounds exhibiting a novel mode of action. Int J Antimicrob Agents. 2003 Sep;22(3):318-31.
• [13] Synthesis and binding affinity of 2-phenylimidazo[1,2-alpha]pyridine derivatives for both central and peripheral benzodiazepine receptors. A new se... J Med Chem. 1997 Sep 12;40(19):3109-18.
• [14] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
• [15] DP-VPA D-Pharm. Curr Opin Investig Drugs. 2002 Jun;3(6):921-3.
• [16] Structural requirements for agonist actions at the benzodiazepine receptor: studies with analogues of 6-(benzyloxy)-4-(methoxymethyl)-beta-carbolin... J Med Chem. 1990 Mar;33(3):1062-9.
• [17] Involvement of aryl hydrocarbon receptor in the cytotoxicity of corannulene and its derivatives. Toxicol Lett. 2020 Mar 15;321:114-121. doi: 10.1016/j.toxlet.2019.12.012. Epub 2019 Dec 9.
• [18] Ameliorative effects of SLC22A2 gene polymorphism 808 G/T and cimetidine on cisplatin-induced nephrotoxicity in Chinese cancer patients. Food Chem Toxicol. 2012 Jul;50(7):2289-93. doi: 10.1016/j.fct.2012.03.077. Epub 2012 Apr 16.
• [19] A species difference in the transport activities of H2 receptor antagonists by rat and human renal organic anion and cation transporters. J Pharmacol Exp Ther. 2005 Oct;315(1):337-45.
• [20] Transport of lamivudine [(-)-beta-L-2',3'-dideoxy-3'-thiacytidine] and high-affinity interaction of nucleoside reverse transcriptase inhibitors with human organic cation transporters 1, 2, and 3. J Pharmacol Exp Ther. 2009 Apr;329(1):252-61. doi: 10.1124/jpet.108.146225. Epub 2009 Jan 13.
• [21] Interactions of human organic anion transporters and human organic cation transporters with nonsteroidal anti-inflammatory drugs. J Pharmacol Exp Ther. 2002 Nov;303(2):534-9.
• [22] Expression of drug transporters and drug metabolizing enzymes in the bladder urothelium in man and affinity of the bladder spasmolytic trospium chloride to transporters likely involved in its pharmacokinetics. Mol Pharm. 2015 Jan 5;12(1):171-8.
• [23] Expression and pharmacological profile of the human organic cation transporters hOCT1, hOCT2 and hOCT3. Br J Pharmacol. 2002 Jul;136(6):829-36.
• [24] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [25] Differential substrate and inhibitory activities of ranitidine and famotidine toward human organic cation transporter 1 (hOCT1; SLC22A1), hOCT2 (SLC22A2), and hOCT3 (SLC22A3). J Pharmacol Exp Ther. 2005 Dec;315(3):1288-97.
• [26] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [27] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [28] The pregnane X receptor down-regulates organic cation transporter 1 (SLC22A1) in human hepatocytes by competing for ("squelching") SRC-1 coactivator. Br J Pharmacol. 2016 May;173(10):1703-15. doi: 10.1111/bph.13472. Epub 2016 Apr 8.
• [29] Selective transport of monoamine neurotransmitters by human plasma membrane monoamine transporter and organic cation transporter 3. J Pharmacol Exp Ther. 2010 Dec;335(3):743-53. doi: 10.1124/jpet.110.170142. Epub 2010 Sep 21.
• [30] Time series analysis of oxidative stress response patterns in HepG2: a toxicogenomics approach. Toxicology. 2013 Apr 5;306:24-34.
• [31] 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.
• [32] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [33] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [34] Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium. Mol Hum Reprod. 2007 Sep;13(9):641-54.
• [35] Cannabidiol enhances cytotoxicity of anti-cancer drugs in human head and neck squamous cell carcinoma. Sci Rep. 2020 Nov 26;10(1):20622. doi: 10.1038/s41598-020-77674-y.
• [36] Evidence of securin-mediated resistance to gefitinib-induced apoptosis in human cancer cells. Chem Biol Interact. 2013 Apr 25;203(2):412-22. doi: 10.1016/j.cbi.2013.03.011. Epub 2013 Mar 22.
• [37] Cigarette smoke and asbestos activate poly-ADP-ribose polymerase in alveolar epithelial cells. J Investig Med. 2001 Jan;49(1):68-76. doi: 10.2310/6650.2001.34092.
• [38] Apoptotic signaling pathways induced by nitric oxide in human lymphoblastoid cells expressing wild-type or mutant p53. Cancer Res. 2004 May 1;64(9):3022-9. doi: 10.1158/0008-5472.can-03-1880.
• [39] The antidepressants imipramine, clomipramine, and citalopram induce apoptosis in human acute myeloid leukemia HL-60 cells via caspase-3 activation. J Biochem Mol Toxicol. 1999;13(6):338-47. doi: 10.1002/(sici)1099-0461(1999)13:6<338::aid-jbt8>3.0.co;2-7.
• [40] Ciprofloxacin mediated cell growth inhibition, S/G2-M cell cycle arrest, and apoptosis in a human transitional cell carcinoma of the bladder cell line. Clin Cancer Res. 2000 Mar;6(3):891-900.
• [41] Investigation of molecular mechanisms underlying the antiproliferative effects of colchicine against PC3 prostate cancer cells. Toxicol In Vitro. 2021 Jun;73:105138. doi: 10.1016/j.tiv.2021.105138. Epub 2021 Mar 6.
• [42] Sulindac enhances adenoviral vector expressing mda-7/IL-24-mediated apoptosis in human lung cancer. Mol Cancer Ther. 2005 Feb;4(2):291-304.
• [43] Methotrexate induces poly(ADP-ribose) polymerase-dependent, caspase 3-independent apoptosis in subsets of proliferating CD4+ T cells. Clin Exp Immunol. 2007 May;148(2):288-95. doi: 10.1111/j.1365-2249.2007.03335.x. Epub 2007 Feb 7.