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

General Information of Drug (ID: DM58XJN)

• Drug Name: Desmethylastemizole Drug Info
• Synonyms: O-Desmethyl Astemizole; 73736-50-2; UNII-L460QHM1YN; L460QHM1YN; CHEMBL60796; Demethylastemizole; 4-[2-[4-[[1-[(4-fluorophenyl)methyl]benzimidazol-2-yl]amino]piperidin-1-yl]ethyl]phenol; Desmethylasteizole; R-44-271; R 44 271; O-Demethylastemizole; O-Desmethylastemizole; AC1L4F06; SCHEMBL1152697; CTK8G2140; DTXSID10224058; LAGYWHSFHIMTPE-UHFFFAOYSA-N; ZINC13537287; BDBM50131433; AKOS030240026; Phenol, 4-(2-(4-((1-((4-fluorophenyl)methyl)-1H-benzimidazol-2-yl)amino)-1-piperidinyl)ethyl)-; FT-0666079; R 44271; DESMETHEYLASTEMIZOLE

Indication

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

• Cross-matching ID:
  PubChem CID: 155805
  CAS Number: CAS 73736-50-2
  TTD Drug ID: DM58XJN
  INTEDE Drug ID: DR1859

Molecule-Related Drug Atlas

Drug(s) Targeting Voltage-gated potassium channel Kv11.1 (KCNH2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
VESNARINONE	DMBKX3C	Cardiac failure	BD10-BD13	Approved	[1]
M100907	DM7ZFBA	Sleep-wake disorder	7A00-7B2Z	Phase 3	[5]
HP-184	DMNOMV2	Multiple sclerosis	8A40	Phase 2	[6]
NITD609	DMQHBSX	Malaria	1F40-1F45	Phase 2	[7]
ABT-229	DMN3S1B	Pain	MG30-MG3Z	Phase 2	[8]
ISOQUINE	DMR17YI	Malaria	1F40-1F45	Phase 1	[9]
Pyrido[3,2-e][1,2,4]triazolo[4,3-a]pyrazine derivative 1	DMC8935	N. A.	N. A.	Patented	[10]
Isoindoline derivative 5	DMIUTQW	N. A.	N. A.	Patented	[11]
Isoindoline derivative 3	DM2MYL9	N. A.	N. A.	Patented	[11]
Isoindoline derivative 4	DMP1NKI	N. A.	N. A.	Patented	[11]

Drug(s) Metabolized By Cytochrome P450 2J2 (CYP2J2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Riociguat	DMXBLMP	Chronic thromboembolic pulmonary hypertension		Approved	[12]
Rivaroxaban	DMQMBZ1	Deep vein thrombosis	BD71	Approved	[13]
Ergocalciferol	DMHO0AR	Hypoparathyroidism	5A50	Approved	[14]
Vorapaxar	DMA16BR	Myocardial infarction	BA41-BA43	Approved	[15]
Vitamin D	DMWQUC9	N. A.	N. A.	Approved	[14]
Alfacalcidol	DM1237M	Hyperparathyroidism	5A51	Phase 4	[14]
Ebastine	DMH21D9	N. A.	N. A.	Phase 4	[16]
MANIDIPINE	DMJPGUA	N. A.	N. A.	Phase 3	[17]
Carebastine	DMUVMWZ	Ocular allergy	4A81	Phase 3	[18]
Eperisone	DM1SMAI	Muscle spasm	MB47.3	Phase 3	[19]

Drug(s) Affected By Potassium voltage-gated channel subfamily H member 1 (KCNH1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[20]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[21]
Zoledronate	DMIXC7G	Adenocarcinoma	2D40	Approved	[22]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[23]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[20]
Resveratrol	DM3RWXL	Giant cell arteritis	4A44.2	Phase 3	[24]
(+)-JQ1	DM1CZSJ	Testicular cancer	2C80	Phase 1	[25]
Benzo(a)pyrene	DMN7J43	N. A.	N. A.	Phase 1	[26]
Astemizole	DM2HN6Q	Allergic rhinitis	CA08.0	Withdrawn from market	[27]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Voltage-gated potassium channel Kv11.1 (KCNH2)	TTQ6VDM	KCNH2_HUMAN	Blocker	[2]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2J2 (CYP2J2) Main DME	DERSX5P	CP2J2_HUMAN	Substrate	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Potassium voltage-gated channel subfamily H member 1 (KCNH1)	OTZZXWER	KCNH1_HUMAN	Gene/Protein Processing	[4]

References

• [1] Prediction of hERG potassium channel affinity by traditional and hologram qSAR methods. Bioorg Med Chem Lett. 2003 Aug 18;13(16):2773-5.
• [2] Block of HERG potassium channels by the antihistamine astemizole and its metabolites desmethylastemizole and norastemizole. J Cardiovasc Electrophysiol. 1999 Jun;10(6):836-43.
• [3] Involvement of CYP2J2 on the intestinal first-pass metabolism of antihistamine drug, astemizole. Drug Metab Dispos. 2002 Nov;30(11):1240-5.
• [4] A clinical drug library screen identifies astemizole as an antimalarial agent. Nat Chem Biol. 2006 Aug;2(8):415-6. doi: 10.1038/nchembio806. Epub 2006 Jul 2.
• [5] Non-basic ligands for aminergic GPCRs: the discovery and development diaryl sulfones as selective, orally bioavailable 5-HT2A receptor antagonists ... Bioorg Med Chem Lett. 2010 Jun 15;20(12):3708-12.
• [6] Emerging drugs for spinal cord injury. Expert Opin Emerg Drugs. 2008 Mar;13(1):63-80.
• [7] Spiroindolones, a potent compound class for the treatment of malaria. Science. 2010 Sep 3;329(5996):1175-80.
• [8] 9-Dihydroerythromycin ethers as motilin agonists--developing structure-activity relationships for potency and safety. Bioorg Med Chem. 2010 Nov 1;18(21):7651-8.
• [9] Candidate selection and preclinical evaluation of N-tert-butyl isoquine (GSK369796), an affordable and effective 4-aminoquinoline antimalarial for ... J Med Chem. 2009 Mar 12;52(5):1408-15.
• [10] Towards selective phosphodiesterase 2A (PDE2A) inhibitors: a patent review (2010 - present).Expert Opin Ther Pat. 2016 Aug;26(8):933-46.
• [11] The sigma-2 (-2) receptor: a review of recent patent applications: 2013-2018.Expert Opin Ther Pat. 2018 Sep;28(9):655-663.
• [12] Riociguat (adempas): a novel agent for the treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. P T. 2014 Nov;39(11):749-58.
• [13] Comparative efficacy and safety of the novel oral anticoagulants dabigatran, rivaroxaban and apixaban in preclinical and clinical development. Thromb Haemost. 2010 Mar;103(3):572-85.
• [14] Characterization of rat and human CYP2J enzymes as Vitamin D 25-hydroxylases. Steroids. 2006 Oct;71(10):849-56.
• [15] Vorapaxar: the missing link in antiplatelet therapy! J Anaesthesiol Clin Pharmacol. 2017 Apr-Jun;33(2):269-270.
• [16] Identifying a selective substrate and inhibitor pair for the evaluation of CYP2J2 activity. Drug Metab Dispos. 2012 May;40(5):943-51.
• [17] Inhibitory effects of antihypertensive drugs on human cytochrome P450 2J2 activity: Potent inhibition by azelnidipine and manidipine. Chem Biol Interact. 2019 Jun 1;306:1-9.
• [18] Characterization of ebastine, hydroxyebastine, and carebastine metabolism by human liver microsomes and expressed cytochrome P450 enzymes: major roles for CYP2J2 and CYP3A. Drug Metab Dispos. 2006 Nov;34(11):1793-7.
• [19] Characterization of human cytochrome P450 enzymes involved in the biotransformation of eperisone. Xenobiotica. 2009 Jan;39(1):1-10.
• [20] Estrogens and human papilloma virus oncogenes regulate human ether--go-go-1 potassium channel expression. Cancer Res. 2009 Apr 15;69(8):3300-7. doi: 10.1158/0008-5472.CAN-08-2036. Epub 2009 Apr 7.
• [21] 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.
• [22] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [23] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [24] A novel long noncoding RNA AK001796 acts as an oncogene and is involved in cell growth inhibition by resveratrol in lung cancer. Toxicol Appl Pharmacol. 2015 Jun 1;285(2):79-88.
• [25] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [26] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [27] Functional and molecular identification of intermediate-conductance Ca(2+)-activated K(+) channels in breast cancer cells: association with cell cycle progression. Am J Physiol Cell Physiol. 2004 Jul;287(1):C125-34. doi: 10.1152/ajpcell.00488.2003. Epub 2004 Feb 25.