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

General Information of Drug (ID: DMZVMKF)

• Drug Name: Alfuzosin Drug Info
• Synonyms: Alfusosine; Alfuzosina; Alfuzosine; Alfuzosinum; Alphuzosine; Alfuzosina [Spanish]; Alfuzosine [French]; Alfuzosinum [Latin]; Alfuzosin (INN); Alfuzosin [INN:BAN]; Xatral (TN); N-[3-[(4-amino-6,7-dimethoxyquinazolin-2-yl)-methylamino]propyl]oxolane-2-carboxamide; N-(3-((4-Amino-6,7-dimethoxy-2-quinazolinyl)methylamino)propyl)tetrahydro-2-furancarboxamide; N-{3-[(4-amino-6,7-dimethoxyquinazolin-2-yl)(methyl)amino]propyl}tetrahydrofuran-2-carboxamide

Indication

Disease Entry	ICD 11	Status	REF
Benign prostatic hyperplasia	GA90	Approved	[1]
Multiple sclerosis	8A40	Approved	[2]
Urinary retention	MF50.3	Approved	[2]

• Therapeutic Class: Antihypertensive Agents
• Cross-matching ID:
  PubChem CID: 2092
  ChEBI ID: CHEBI:51141
  CAS Number: CAS 81403-80-7
  TTD Drug ID: DMZVMKF
  VARIDT Drug ID: DR01382
  ACDINA Drug ID: D00018

Molecule-Related Drug Atlas

Drug(s) Targeting Adrenergic receptor alpha-1D (ADRA1D)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxazosin	DM9PLRH	Benign prostatic hyperplasia	GA90	Approved	[7]
Armodafinil	DMGB035	Malignant glioma	2A00.0	Approved	[8]
Moxisylyte	DMFCLYW	Erectile dysfunction	HA01.1	Approved	[9]
Terazosin	DM3JCVS	Benign prostatic hyperplasia	GA90	Approved	[10]
Bunazosin	DM4I8O7	Glaucoma/ocular hypertension	9C61	Approved	[11]
Trimazosin	DM1QLST	Congestive heart failure	BD10	Approved	[12]
MEDETOMIDINE	DMX9Y7V	Pain	MG30-MG3Z	Phase 2	[13]
DL-017	DMM8GZT	Hypertension	BA00-BA04	Phase 1	[14]
PMID30124346-Compound-LDT8	DM5MUNG	Benign prostatic hyperplasia	GA90	Patented	[15]
PMID30124346-Compound-LDT66	DMJMTNL	Benign prostatic hyperplasia	GA90	Patented	[15]

Drug(s) Transported By Breast cancer resistance protein (ABCG2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[16]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[17]
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[18]
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[19]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[20]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[21]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[22]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[21]
Sulfasalazine	DMICA9H	Irritable bowel syndrome	DD91.0	Approved	[23]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[24]

Drug(s) Affected By Alpha-1D adrenergic receptor (ADRA1D)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[25]
Epinephrine	DM3KJBC	Acute asthma	CA23	Approved	[26]
Oxymetazoline	DM8ZXT6	Arrhythmia	BC9Z	Approved	[27]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[28]
Terbutaline	DMD4381	Asthma	CA23	Approved	[29]
Methoxamine	DMF5XQH	Hypertension	BA00-BA04	Approved	[27]
Quinidine	DMLPICK	N. A.	N. A.	Approved	[25]
Dexamethasone	DMMWZET	Acute adrenal insufficiency		Approved	[29]
Norepinephrine	DMOUC09	Alopecia	ED70	Approved	[27]
Decitabine	DMQL8XJ	Acute myelogenous leukaemia	2A41	Approved	[30]

Drug(s) Affected By Alpha-1A adrenergic receptor (ADRA1A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tamsulosin	DM5QF9V	Benign prostatic hyperplasia	GA90	Approved	[5]
SILODOSIN	DMJSBT6	Benign prostatic hyperplasia	GA90	Approved	[26]
Gabapentin	DM6T924	Complex partial seizure	8A68.0	Approved	[31]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[25]
Epinephrine	DM3KJBC	Acute asthma	CA23	Approved	[26]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[32]
Oxymetazoline	DM8ZXT6	Arrhythmia	BC9Z	Approved	[5]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[33]
Quinidine	DMLPICK	N. A.	N. A.	Approved	[25]
Norepinephrine	DMOUC09	Alopecia	ED70	Approved	[6]

Drug(s) Affected By Alpha-1B adrenergic receptor (ADRA1B)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[25]
Epinephrine	DM3KJBC	Acute asthma	CA23	Approved	[26]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[34]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[35]
Oxymetazoline	DM8ZXT6	Arrhythmia	BC9Z	Approved	[36]
Terbutaline	DMD4381	Asthma	CA23	Approved	[29]
Quinidine	DMLPICK	N. A.	N. A.	Approved	[25]
Dexamethasone	DMMWZET	Acute adrenal insufficiency		Approved	[29]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[37]
Arsenic	DMTL2Y1	N. A.	N. A.	Approved	[38]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Adrenergic receptor alpha-1D (ADRA1D)	TT34BHT	ADA1D_HUMAN	Antagonist	[3]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[4]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Alpha-1A adrenergic receptor (ADRA1A)	OTUIWCL5	ADA1A_HUMAN	Protein Interaction/Cellular Processes	[5]
Alpha-1B adrenergic receptor (ADRA1B)	OTSAYAFD	ADA1B_HUMAN	Protein Interaction/Cellular Processes	[6]
Alpha-1D adrenergic receptor (ADRA1D)	OTW2CD1O	ADA1D_HUMAN	Protein Interaction/Cellular Processes	[6]

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: 7109).
• [2] Alfuzosin FDA Label
• [3] Alfuzosin: a review of the therapeutic use of the prolonged-release formulation given once daily in the management of benign prostatic hyperplasia. Drugs. 2002;62(4):633-53.
• [4] In vitro and in vivo evidence for the importance of breast cancer resistance protein transporters (BCRP/MXR/ABCP/ABCG2). Handb Exp Pharmacol. 2011;(201):325-71.
• [5] Cell membrane chromatography competitive binding analysis for characterization of 1A adrenoreceptor binding interactions. Anal Bioanal Chem. 2011 Jul;400(10):3625-33. doi: 10.1007/s00216-011-5026-z. Epub 2011 May 5.
• [6] The alpha 1-adrenergic receptor that mediates smooth muscle contraction in human prostate has the pharmacological properties of the cloned human alpha 1c subtype. Mol Pharmacol. 1994 Apr;45(4):703-8.
• [7] The role of combination medical therapy in benign prostatic hyperplasia. Int J Impot Res. 2008 Dec;20 Suppl 3:S33-43.
• [8] Mechanisms of modafinil: A review of current research. Neuropsychiatr Dis Treat. 2007 June; 3(3): 349-364.
• [9] Pharmacokinetics of moxisylyte in healthy volunteers after intracavernous injection of increasing doses. Eur J Clin Pharmacol. 1996;49(5):411-5.
• [10] Induction of prostate apoptosis by alpha1-adrenoceptor antagonists: mechanistic significance of the quinazoline component. Prostate Cancer Prostatic Dis. 2002;5(2):88-95.
• [11] Bunazosin, a selective alpha1-adrenoceptor antagonist, as an anti-glaucoma drug: effects on ocular circulation and retinal neuronal damage. Cardiovasc Drug Rev. 2005 Spring;23(1):43-56.
• [12] The hypotensive effect of trimazosin is not caused solely by alpha 1-adrenoceptor blockade. J Cardiovasc Pharmacol. 1984 Jan-Feb;6(1):142-50.
• [13] A structure-activity relationship study of benzylic modifications of 4-[1-(1-naphthyl)ethyl]-1H-imidazoles on alpha 1- and alpha 2-adrenergic recep... J Med Chem. 1994 Jul 22;37(15):2328-33.
• [14] Antihypertensive action and blockade of alpha1-adrenoceptors by DL-017, a quinazoline derivative. J Cardiovasc Pharmacol. 2001 Dec;38(6):893-9.
• [15] 5-HT1A receptor ligands and their therapeutic applications: review of new patents.Expert Opin Ther Pat. 2018 Sep;28(9):679-689.
• [16] Doxorubicin transport by RALBP1 and ABCG2 in lung and breast cancer. Int J Oncol. 2007 Mar;30(3):717-25.
• [17] Wild-type breast cancer resistance protein (BCRP/ABCG2) is a methotrexate polyglutamate transporter. Cancer Res. 2003 Sep 1;63(17):5538-43.
• [18] The effect of low pH on breast cancer resistance protein (ABCG2)-mediated transport of methotrexate, 7-hydroxymethotrexate, methotrexate diglutamate, folic acid, mitoxantrone, topotecan, and resveratrol in in vitro drug transport models. Mol Pharmacol. 2007 Jan;71(1):240-9.
• [19] Role of BCRP as a biomarker for predicting resistance to 5-fluorouracil in breast cancer. Cancer Chemother Pharmacol. 2009 May;63(6):1103-10.
• [20] Inhibiting the function of ABCB1 and ABCG2 by the EGFR tyrosine kinase inhibitor AG1478. Biochem Pharmacol. 2009 Mar 1;77(5):781-93.
• [21] Sterol transport by the human breast cancer resistance protein (ABCG2) expressed in Lactococcus lactis. J Biol Chem. 2003 Jun 6;278(23):20645-51.
• [22] The phytoestrogen genistein enhances multidrug resistance in breast cancer cell lines by translational regulation of ABC transporters. Cancer Lett. 2016 Jun 28;376(1):165-72.
• [23] Curcumin inhibits the activity of ABCG2/BCRP1, a multidrug resistance-linked ABC drug transporter in mice. Pharm Res. 2009 Feb;26(2):480-7.
• [24] Imatinib mesylate (STI571) is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump. Blood. 2004 Nov 1;104(9):2940-2.
• [25] Effects of quinidine and verapamil on human cardiovascular alpha1-adrenoceptors. Circulation. 1998 Apr 7;97(13):1227-30. doi: 10.1161/01.cir.97.13.1227.
• [26] Carvedilol selectively inhibits oscillatory intracellular calcium changes evoked by human alpha1D- and alpha1B-adrenergic receptors. Cardiovasc Res. 2004 Sep 1;63(4):662-72. doi: 10.1016/j.cardiores.2004.05.014.
• [27] Chromatography studies on bio-affinity of nine ligands of alpha1-adrenoceptor to alpha1D subtypes overexpressed in cell membrane. Sci China C Life Sci. 2004 Aug;47(4):376-81. doi: 10.1360/03yc0109.
• [28] 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.
• [29] Neuroendocrine mediators up-regulate alpha1b- and alpha1d-adrenergic receptor subtypes in human monocytes. J Neuroimmunol. 1999 Mar 1;95(1-2):165-73. doi: 10.1016/s0165-5728(99)00011-9.
• [30] Epigenetic regulation of human alpha1d-adrenergic receptor gene expression: a role for DNA methylation in Sp1-dependent regulation. FASEB J. 2007 Jul;21(9):1979-93. doi: 10.1096/fj.06-7118com. Epub 2007 Mar 23.
• [31] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [32] Adipogenic Effects and Gene Expression Profiling of Firemaster? 550 Components in Human Primary Preadipocytes. Environ Health Perspect. 2017 Sep 14;125(9):097013. doi: 10.1289/EHP1318.
• [33] 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.
• [34] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [35] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [36] Alpha-adrenoceptor agonistic activity of oxymetazoline and xylometazoline. Fundam Clin Pharmacol. 2010 Dec;24(6):729-39.
• [37] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [38] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.