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

General Information of Drug (ID: DM014WS)

• Drug Name: EHNA Drug Info
• Synonyms: erythro-9-(2-hydroxy-3-nonyl)adenine hydrochloride

Indication

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

• Cross-matching ID:
  PubChem CID: 3206
  CAS Number: CAS 59262-86-1
  TTD Drug ID: DM014WS

Molecule-Related Drug Atlas

Drug(s) Targeting Adenosine deaminase (ADA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cladribine	DM3JDRP	Hairy cell leukaemia	2A82.2	Approved	[6]
Elapegademase	DMS7OU8	Adenosine deaminase defciency	4A01.1	Approved	[7]
Fludarabine	DMVRLT7	Acute myelogenous leukaemia	2A41	Approved	[8]
Pentostatin	DM0HXDS	Acute graft versus host disease	4B24.0	Approved	[8]
GSK2696273	DMP5O1U	Chronic pain	MG30	Preregistration	[9]
OTL-101	DMLMS6J	Severe combined immunodeficiency	4A01.10	Phase 3	[10]
Ex vivo adenosine deaminase-transduced hematopoietic stem cell therapy	DMIREUZ	Immunodeficiency	4A00-4A85	Phase 1/2	[9]
3-(6-Amino-purin-9-yl)-6-phenyl-hexan-2-ol	DMZT8QX	Discovery agent	N.A.	Investigative	[11]
3-(6-Amino-purin-9-yl)-8-phenyl-octan-2-ol	DMAIS1D	Discovery agent	N.A.	Investigative	[11]
1-Deaza-Adenosine	DMG0VN6	Discovery agent	N.A.	Investigative	[12]

Drug(s) Targeting Phosphodiesterase 2A (PDE2A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tofisopam	DMTGNWU	Hyperuricaemia	5C55.Y	Phase 2	[13]
CP-461	DMEYMTX	Inflammatory bowel disease	DD72	Phase 2	[14]
ND7001	DMUBTC6	Mood disorder	6A60-6E23	Phase 1	[15]
Pyrido[3,2-e][1,2,4]triazolo[4,3-a]pyrazine derivative 1	DMC8935	N. A.	N. A.	Patented	[16]
Pyrido[3,2-e][1,2,4]triazolo[4,3-a]pyrazine derivative 2	DM4CSBD	N. A.	N. A.	Patented	[16]
Imidazo[5,1-c]pyrido[2,3-e][1,2,4]triazine derivative 2	DMS3ROL	N. A.	N. A.	Patented	[16]
Triazolo-pyridine derivative 5	DM1R205	N. A.	N. A.	Patented	[16]
PMID27321640-Compound-58	DM0NYK3	N. A.	N. A.	Patented	[16]
Triazolo-pyridine derivative 4	DM5ZQKS	N. A.	N. A.	Patented	[16]
Imidazo[5,1-c]pyrido[2,3-e][1,2,4]triazine derivative 3	DMZ61T8	N. A.	N. A.	Patented	[16]

Drug(s) Affected By C-C motif chemokine 2 (CCL2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Indinavir	DM0T3YH	Human immunodeficiency virus infection	1C62	Approved	[17]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[18]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[19]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[20]
Imiquimod	DM1TMA3	Alopecia areata	ED70.2	Approved	[21]
Methimazole	DM25FL8	Hyperthyroidism	5A02	Approved	[22]
TECFIDERA	DM2OVDT	Multiple sclerosis	8A40	Approved	[23]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[24]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[25]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[26]

Drug(s) Affected By Interleukin-13 (IL13)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[27]
Prednisone	DM2HG4X	Acute asthma	CA23	Approved	[28]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[29]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[30]
Rifampicin	DM5DSFZ	Non-insulin dependent diabetes	5A11	Approved	[31]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[32]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[33]
Budesonide	DMJIBAW	Allergic rhinitis	CA08.0	Approved	[34]
Alitretinoin	DMME8LH	Kaposi sarcoma	2B57	Approved	[30]
Ethambutol	DMR87LC	Pulmonary tuberculosis	1B10.Z	Approved	[31]

Drug(s) Affected By Potassium voltage-gated channel subfamily H member 2 (KCNH2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Metoclopramide	DMFA5MY	Nausea	MD90	Approved	[35]
Quinidine	DMLPICK	N. A.	N. A.	Approved	[36]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[37]
Erythromycin	DM4K7GQ	Acne vulgaris	ED80	Approved	[38]
Clarithromycin	DM4M1SG	Acute maxillary sinusitis		Approved	[38]
Disopyramide	DM5SYZP	Long QT syndrome	BC65.0	Approved	[39]
Propranolol	DM79NTF	Angina pectoris	BA40	Approved	[40]
Amiodarone	DMUTEX3	Tachyarrhythmias	BC71	Approved	[41]
Dofetilide	DMPN1TW	Sinus rhythm disorder	BC9Y	Approved	[42]
Flecainide	DMSQDLE	Tachyarrhythmias	BC71	Approved	[38]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Adenosine deaminase (ADA)	TTLP57V	ADA_HUMAN	Inhibitor	[2]
Phosphodiesterase 2A (PDE2A)	TTJGW1Z	PDE2A_HUMAN	Inhibitor	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Protein Interaction/Cellular Processes	[4]
Interleukin-13 (IL13)	OTI4YS3Y	IL13_HUMAN	Protein Interaction/Cellular Processes	[4]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Gene/Protein Processing	[5]

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: 5179).
• [2] Tight-binding inhibitors--IV. Inhibition of adenosine deaminases by various inhibitors. Biochem Pharmacol. 1977 Mar 1;26(5):359-67.
• [3] Rapid regulation of PDE-2 and PDE-4 cyclic AMP phosphodiesterase activity following ligation of the T cell antigen receptor on thymocytes: analysis using the selective inhibitors erythro-9-(2-hydroxy-3-nonyl)-adenine (EHNA) and rolipram. Cell Signal. 1996 Feb;8(2):97-110.
• [4] Adenosine deaminase 1 and concentrative nucleoside transporters 2 and 3 regulate adenosine on the apical surface of human airway epithelia: implications for inflammatory lung diseases. Biochemistry. 2007 Sep 11;46(36):10373-83. doi: 10.1021/bi7009647. Epub 2007 Aug 15.
• [5] Effects of phosphodiesterase (PDE) inhibitors on human ether-a-go-go related gene (hERG) channel activity. J Appl Toxicol. 2007 Jan-Feb;27(1):78-85. doi: 10.1002/jat.1201.
• [6] Cladribine: from the bench to the bedside--focus on hairy cell leukemia. Expert Rev Anticancer Ther. 2004 Oct;4(5):745-57.
• [7] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
• [8] Purine nucleoside analogs in indolent non-Hodgkin's lymphoma. Oncology (Williston Park). 2000 Jun;14(6 Suppl 2):13-5.
• [9] Clinical pipeline report, company report or official report of GlaxoSmithKline.
• [10] Clinical pipeline report, company report or official report of Orchard Therapeutics.
• [11] Adenosine deaminase inhibitors: synthesis and biological evaluation of unsaturated, aromatic, and oxo derivatives of (+)-erythro-9-(2'S-hydroxy-3'R... J Med Chem. 2000 Nov 30;43(24):4694-700.
• [12] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [13] The atypical anxiolytic drug, tofisopam, selectively blocks phosphodiesterase isoenzymes and is active in the mouse model of negative symptoms of psychosis. J Neural Transm (Vienna). 2010 Nov;117(11):1319-25.
• [14] Sulindac and its derivatives: a novel class of anticancer agents. Curr Opin Investig Drugs. 2001 May;2(5):677-83.
• [15] Phosphodiesterase 2 inhibitors promote axonal outgrowth in organotypic slice co-cultures. Neurosignals. 2013;21(3-4):197-212.
• [16] Towards selective phosphodiesterase 2A (PDE2A) inhibitors: a patent review (2010 - present).Expert Opin Ther Pat. 2016 Aug;26(8):933-46.
• [17] Some HIV antiretrovirals increase oxidative stress and alter chemokine, cytokine or adiponectin production in human adipocytes and macrophages. Antivir Ther. 2007;12(4):489-500.
• [18] Arsenite and cadmium promote the development of mammary tumors. Carcinogenesis. 2020 Jul 14;41(7):1005-1014. doi: 10.1093/carcin/bgz176.
• [19] Crosstalk between alveolar macrophages and alveolar epithelial cells/fibroblasts contributes to the pulmonary toxicity of gefitinib. Toxicol Lett. 2021 Mar 1;338:1-9. doi: 10.1016/j.toxlet.2020.11.011. Epub 2020 Nov 25.
• [20] Oxidative Stress Alters miRNA and Gene Expression Profiles in Villous First Trimester Trophoblasts. Biomed Res Int. 2015;2015:257090. doi: 10.1155/2015/257090. Epub 2015 Aug 3.
• [21] Cannabidiol selectively modulates interleukin (IL)-1 and IL-6 production in toll-like receptor activated human peripheral blood monocytes. Toxicology. 2021 Dec;464:153016. doi: 10.1016/j.tox.2021.153016. Epub 2021 Nov 2.
• [22] Monitoring of deiodinase deficiency based on transcriptomic responses in SH-SY5Y cells. Arch Toxicol. 2013 Jun;87(6):1103-13. doi: 10.1007/s00204-013-1018-4. Epub 2013 Feb 10.
• [23] Dimethyl Fumarate Inhibits the Nuclear Factor B Pathway in Breast Cancer Cells by Covalent Modification of p65 Protein. J Biol Chem. 2016 Feb 12;291(7):3639-47. doi: 10.1074/jbc.M115.679704. Epub 2015 Dec 18.
• [24] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [25] Simvastatin reduces expression of cytokines interleukin-6, interleukin-8, and monocyte chemoattractant protein-1 in circulating monocytes from hypercholesterolemic patients. Arterioscler Thromb Vasc Biol. 2002 Jul 1;22(7):1194-9. doi: 10.1161/01.atv.0000022694.16328.cc.
• [26] Plant polyphenols differentially modulate inflammatory responses of human keratinocytes by interfering with activation of transcription factors NFB and AhR and EGFR-ERK pathway. Toxicol Appl Pharmacol. 2011 Sep 1;255(2):138-49.
• [27] Benzyl isothiocyanate attenuates the hydrogen peroxide-induced interleukin-13 expression through glutathione S-transferase P induction in T lymphocytic leukemia cells. J Biochem Mol Toxicol. 2018 Jun;32(6):e22054.
• [28] Alterations in eotaxin, monocyte chemoattractant protein-4, interleukin-5, and interleukin-13 after systemic steroid treatment for nasal polyps. Otolaryngol Head Neck Surg. 2004 Nov;131(5):585-9. doi: 10.1016/j.otohns.2004.05.028.
• [29] Editor's Highlight: Modeling Compound-Induced Fibrogenesis In Vitro Using Three-Dimensional Bioprinted Human Liver Tissues. Toxicol Sci. 2016 Dec;154(2):354-367. doi: 10.1093/toxsci/kfw169. Epub 2016 Sep 7.
• [30] Direct and indirect effects of retinoic acid on human Th2 cytokine and chemokine expression by human T lymphocytes. BMC Immunol. 2006 Nov 21;7:27. doi: 10.1186/1471-2172-7-27.
• [31] Detection of Drug-Responsive T-Lymphocytes in a Case of Fatal Antituberculosis Drug-Related Liver Injury. Chem Res Toxicol. 2016 Nov 21;29(11):1793-1795. doi: 10.1021/acs.chemrestox.6b00393. Epub 2016 Nov 9.
• [32] Inhibition of interleukin-13 gene expression in T cells through GATA-3 pathway by arsenic trioxide. Chin Med J (Engl). 2008 Nov 20;121(22):2346-9.
• [33] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [34] [Effects of beclomethasone dipropionate and budesonide on interleukin-13 induced cytokine release, proliferation and differentiation of the human lung fibroblasts]. Zhonghua Jie He He Hu Xi Za Zhi. 2007 Aug;30(8):599-604.
• [35] Comparison of the effects of metoclopramide and domperidone on HERG channels. Pharmacology. 2005 Apr;74(1):31-6. doi: 10.1159/000083234. Epub 2005 Jan 7.
• [36] Further insights into the effect of quinidine in short QT syndrome caused by a mutation in HERG. J Cardiovasc Electrophysiol. 2005 Jan;16(1):54-8. doi: 10.1046/j.1540-8167.2005.04470.x.
• [37] Automated tight seal electrophysiology for assessing the potential hERG liability of pharmaceutical compounds. Assay Drug Dev Technol. 2004 Oct;2(5):497-506. doi: 10.1089/adt.2004.2.497.
• [38] Refining the human iPSC-cardiomyocyte arrhythmic risk assessment model. Toxicol Sci. 2013 Dec;136(2):581-94. doi: 10.1093/toxsci/kft205. Epub 2013 Sep 19.
• [39] Pharmacology of the short QT syndrome N588K-hERG K+ channel mutation: differential impact on selected class I and class III antiarrhythmic drugs. Br J Pharmacol. 2008 Nov;155(6):957-66. doi: 10.1038/bjp.2008.325. Epub 2008 Aug 25.
• [40] Comparison of HERG channel blocking effects of various beta-blockers-- implication for clinical strategy. Br J Pharmacol. 2006 Mar;147(6):642-52. doi: 10.1038/sj.bjp.0706508.
• [41] Inhibitory effects of the class III antiarrhythmic drug amiodarone on cloned HERG potassium channels. Naunyn Schmiedebergs Arch Pharmacol. 1999 Mar;359(3):212-9. doi: 10.1007/pl00005344.
• [42] Redox state dependency of HERGS631C channel pharmacology: relation to C-type inactivation. FEBS Lett. 2000 May 26;474(1):111-5. doi: 10.1016/s0014-5793(00)01586-6.