Details of the Drug Combination

General Information of Drug Combination (ID: DCUTDR3)

• Drug Combination Name: Omacetaxine mepesuccinate + Verapamil
• Indication: Hepatoblastoma; Status: Investigative [1]
• Component Drugs:
  Omacetaxine mepesuccinate (DMPU2WX): Small molecular drug
  Verapamil (DMA7PEW): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: HB3
  Zero Interaction Potency (ZIP) Score: 5.739
  Bliss Independence Score: 9.193
  Loewe Additivity Score: 1.014
  LHighest Single Agent (HSA) Score: 7.261

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Omacetaxine mepesuccinate

Disease Entry	ICD 11	Status	REF
Adult acute monocytic leukemia	N.A.	Approved	[2]
Chronic myelogenous leukaemia	2A20.0	Approved	[2]
Chronic myeloid leukaemia	2A20	Approved	[3]
Leukemia	N.A.	Approved	[2]

Omacetaxine mepesuccinate Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Ribosome A (hRA)	TTA4FIU	NOUNIPROTAC	Modulator	[7]

Omacetaxine mepesuccinate Interacts with 29 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Inhibitor of nuclear factor kappa-B kinase subunit alpha (CHUK)	OTLF4ZB1	IKKA_HUMAN	Increases Phosphorylation	[8]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Expression	[8]
Cyclin-dependent kinase 1 (CDK1)	OTW1SC2N	CDK1_HUMAN	Increases Expression	[9]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[10]
G2/mitotic-specific cyclin-B1 (CCNB1)	OT19S7E5	CCNB1_HUMAN	Decreases Expression	[9]
Cyclin-A2 (CCNA2)	OTPHHYZJ	CCNA2_HUMAN	Decreases Expression	[9]
G1/S-specific cyclin-E1 (CCNE1)	OTLD7UID	CCNE1_HUMAN	Increases Expression	[9]
Cyclin-dependent kinase 2 (CDK2)	OTB5DYYZ	CDK2_HUMAN	Increases Expression	[9]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[9]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[9]
Hematopoietic progenitor cell antigen CD34 (CD34)	OT1MOFLZ	CD34_HUMAN	Decreases Expression	[8]
ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 (CD38)	OTG0TTX7	CD38_HUMAN	Increases Expression	[8]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Decreases Phosphorylation	[9]
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA)	OTTOMI8J	PK3CA_HUMAN	Decreases Expression	[9]
Serine/threonine-protein kinase mTOR (MTOR)	OTHH8KU7	MTOR_HUMAN	Decreases Phosphorylation	[9]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Cleavage	[9]
Proliferation marker protein Ki-67 (MKI67)	OTA8N1QI	KI67_HUMAN	Decreases Expression	[9]
Neurogenic locus notch homolog protein 1 (NOTCH1)	OTI1WADQ	NOTC1_HUMAN	Increases Expression	[8]
Ephrin type-B receptor 4 (EPHB4)	OTKLPVXJ	EPHB4_HUMAN	Decreases Expression	[9]
Caspase-7 (CASP7)	OTAPJ040	CASP7_HUMAN	Increases Cleavage	[9]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Cleavage	[9]
Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN)	OTOWDUNT	PTEN_HUMAN	Increases Expression	[9]
Nuclear factor NF-kappa-B p100 subunit (NFKB2)	OTS231V7	NFKB2_HUMAN	Increases Expression	[8]
Transcription factor RelB (RELB)	OTU3QYEF	RELB_HUMAN	Increases Expression	[8]
Transcription factor p65 (RELA)	OTUJP9CN	TF65_HUMAN	Increases Expression	[8]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[9]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1)	OT2YYI1A	MCL1_HUMAN	Decreases Expression	[10]
Jouberin (AHI1)	OT8K2YWY	AHI1_HUMAN	Increases Expression	[11]
Bcl2-associated agonist of cell death (BAD)	OT63ERYM	BAD_HUMAN	Increases Expression	[9]

Indication(s) of Verapamil

Disease Entry	ICD 11	Status	REF
Angina pectoris	BA40	Approved	[4]
Atrial fibrillation	BC81.3	Approved	[4]
Classic phenylketonuria	N.A.	Approved	[4]
Hypertension	BA00-BA04	Approved	[5]
Malignant essential hypertension	BA00	Approved	[4]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 2/3	[6]

Verapamil Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Voltage-gated calcium channel alpha Cav3.1 (CACNA1G)	TT729IR	CAC1G_HUMAN	Blocker	[12]
HUMAN two pore channel subtype 2 (TPC2)	TTHQJ2Y	TPC2_HUMAN	Blocker	[13]

Verapamil Interacts with 6 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 1 (ABCC1)	DTSYQGK	MRP1_HUMAN	Substrate	[14]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[15]
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[16]
Multidrug resistance protein 3 (ABCB4)	DTZRMK5	MDR3_HUMAN	Substrate	[17]
Organic cation/carnitine transporter 2 (SLC22A5)	DT3HUVD	S22A5_HUMAN	Substrate	[18]
Organic cation/carnitine transporter 1 (SLC22A4)	DT2EG60	S22A4_HUMAN	Substrate	[19]

Verapamil Interacts with 10 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[20]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[21]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[22]
Cytochrome P450 2E1 (CYP2E1)	DEVDYN7	CP2E1_HUMAN	Metabolism	[23]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[24]
Cytochrome P450 2C18 (CYP2C18)	DEZMWRE	CP2CI_HUMAN	Metabolism	[23]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[25]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[26]
Cytochrome P450 2B6 (CYP2B6)	DEPKLMQ	CP2B6_HUMAN	Metabolism	[23]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[27]

Verapamil Interacts with 41 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Expression	[28]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Decreases Activity	[29]
Cytochrome P450 2C8 (CYP2C8)	OTHCWT42	CP2C8_HUMAN	Decreases Activity	[30]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Decreases Activity	[22]
Cytochrome P450 3A5 (CYP3A5)	OTSXFBXB	CP3A5_HUMAN	Decreases Activity	[22]
Multidrug and toxin extrusion protein 2 (SLC47A2)	OTF2CNRD	S47A2_HUMAN	Decreases Activity	[31]
Dynamin-1-like protein (DNM1L)	OTXK1Q1G	DNM1L_HUMAN	Increases Phosphorylation	[32]
Nuclear receptor subfamily 1 group I member 2 (NR1I2)	OTC5U0N5	NR1I2_HUMAN	Increases Activity	[33]
Organic cation/carnitine transporter 2 (SLC22A5)	OTC36TYB	S22A5_HUMAN	Decreases Activity	[34]
ATP-binding cassette sub-family C member 6 (ABCC6)	OTZT0LKT	MRP6_HUMAN	Decreases Activity	[35]
Metalloproteinase inhibitor 1 (TIMP1)	OTOXC51H	TIMP1_HUMAN	Affects Expression	[36]
Protein c-Fos (FOS)	OTJBUVWS	FOS_HUMAN	Increases Expression	[37]
Natriuretic peptides A (NPPA)	OTMQNTNX	ANF_HUMAN	Increases Expression	[38]
Prolactin (PRL)	OTWFQGX7	PRL_HUMAN	Increases Expression	[39]
Platelet basic protein (PPBP)	OT1FHGQS	CXCL7_HUMAN	Decreases Expression	[40]
Platelet factor 4 (PF4)	OTEMJU68	PLF4_HUMAN	Decreases Expression	[40]
Proto-oncogene tyrosine-protein kinase receptor Ret (RET)	OTLU040A	RET_HUMAN	Affects Expression	[36]
Heme oxygenase 1 (HMOX1)	OTC1W6UX	HMOX1_HUMAN	Increases Expression	[41]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[42]
Clusterin (CLU)	OTQGG0JM	CLUS_HUMAN	Affects Expression	[36]
Neuromodulin (GAP43)	OT2OTGGV	NEUM_HUMAN	Affects Expression	[36]
Phosphatidylcholine translocator ABCB4 (ABCB4)	OTE6PY83	MDR3_HUMAN	Decreases Expression	[43]
Potassium voltage-gated channel subfamily A member 3 (KCNA3)	OTXSP3AA	KCNA3_HUMAN	Decreases Activity	[44]
Galanin peptides (GAL)	OTB3VPTO	GALA_HUMAN	Affects Expression	[36]
Alpha-1D adrenergic receptor (ADRA1D)	OTW2CD1O	ADA1D_HUMAN	Affects Binding	[45]
MHC class II transactivator (CIITA)	OTRJNZFO	C2TA_HUMAN	Affects Expression	[46]
Multidrug resistance-associated protein 1 (ABCC1)	OTGUN89S	MRP1_HUMAN	Decreases Activity	[47]
Alpha-1A adrenergic receptor (ADRA1A)	OTUIWCL5	ADA1A_HUMAN	Affects Binding	[45]
Alpha-1B adrenergic receptor (ADRA1B)	OTSAYAFD	ADA1B_HUMAN	Affects Binding	[45]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[42]
Nuclear factor erythroid 2-related factor 2 (NFE2L2)	OT0HENJ5	NF2L2_HUMAN	Affects Localization	[41]
Multidrug and toxin extrusion protein 1 (SLC47A1)	OTZX0U5Q	S47A1_HUMAN	Decreases Activity	[48]
Potassium voltage-gated channel subfamily D member 3 (KCND3)	OTRPIH7J	KCND3_HUMAN	Decreases Activity	[49]
Voltage-dependent L-type calcium channel subunit alpha-1C (CACNA1C)	OT6KFNMS	CAC1C_HUMAN	Increases Response To Substance	[50]
Potassium voltage-gated channel subfamily KQT member 1 (KCNQ1)	OT8SPJNX	KCNQ1_HUMAN	Increases ADR	[51]
Sodium channel protein type 5 subunit alpha (SCN5A)	OTGYZWR6	SCN5A_HUMAN	Increases ADR	[51]
Calcium-activated potassium channel subunit beta-1 (KCNMB1)	OTO4KNJ4	KCMB1_HUMAN	Affects Response To Substance	[52]
Beta-1 adrenergic receptor (ADRB1)	OTQBWN4U	ADRB1_HUMAN	Affects Response To Substance	[53]
Beta-1 adrenergic receptor (ADRB1)	OTQBWN4U	ADRB1_HUMAN	Increases Response	[53]
Cytochrome P450 2D6 (CYP2D6)	OTZJC802	CP2D6_HUMAN	Increases ADR	[51]
Potassium voltage-gated channel subfamily E member 1 (KCNE1)	OTZNQUW9	KCNE1_HUMAN	Increases ADR	[51]

References

• [1] Loss of function mutations in VARS encoding cytoplasmic valyl-tRNA synthetase cause microcephaly, seizures, and progressive cerebral atrophy.Hum Genet. 2018 Apr;137(4):293-303. doi: 10.1007/s00439-018-1882-3. Epub 2018 Apr 24.
• [2] Omacetaxine mepesuccinate FDA Label
• [3] 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: 7454).
• [4] Verapamil FDA Label
• [5] 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: 2406).
• [6] ClinicalTrials.gov (NCT04351763) Amiodarone or Verapamil in COVID-19 Hospitalized Patients With Symptoms. U.S. National Institutes of Health.
• [7] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [8] Synergistic killing effects of homoharringtonine and arsenic trioxide on acute myeloid leukemia stem cells and the underlying mechanisms. J Exp Clin Cancer Res. 2019 Jul 15;38(1):308. doi: 10.1186/s13046-019-1295-8.
• [9] Homoharringtonine suppresses LoVo cell growth by inhibiting EphB4 and the PI3K/AKT and MAPK/EKR1/2 signaling pathways. Food Chem Toxicol. 2020 Feb;136:110960. doi: 10.1016/j.fct.2019.110960. Epub 2019 Nov 11.
• [10] [Homoharringtonine combined arsenic trioxide induced apoptosis in human multiple myeloma cell line RPMI 8226: an experimental research]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2013 Jun;33(6):834-9.
• [11] [Expression and function of Ahi-1 gene in Jurkat cells]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2009 Apr;17(2):445-9.
• [12] Mechanism of tissue-selective drug action in the cardiovascular system. Mol Interv. 2005 Apr;5(2):84-93.
• [13] Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV. Nat Commun. 2020 Mar 27;11(1):1620.
• [14] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [15] Improved expression and purification of human multidrug resistance protein MDR1 from baculovirus-infected insect cells. Protein Expr Purif. 2009 Jul;66(1):7-14.
• [16] Implications of genetic polymorphisms in drug transporters for pharmacotherapy. Cancer Lett. 2006 Mar 8;234(1):4-33.
• [17] MDR3 P-glycoprotein, a phosphatidylcholine translocase, transports several cytotoxic drugs and directly interacts with drugs as judged by interference with nucleotide trapping. J Biol Chem. 2000 Aug 4;275(31):23530-9.
• [18] Genetic variations of the SLC22A5 gene in the Chinese and Indian populations of Singapore. Drug Metab Pharmacokinet. 2010;25(1):112-9.
• [19] Novel membrane transporter OCTN1 mediates multispecific, bidirectional, and pH-dependent transport of organic cations. J Pharmacol Exp Ther. 1999 May;289(2):768-73.
• [20] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
• [21] Identification of P450 enzymes involved in metabolism of verapamil in humans. Naunyn Schmiedebergs Arch Pharmacol. 1993 Sep;348(3):332-7.
• [22] Differential mechanism-based inhibition of CYP3A4 and CYP3A5 by verapamil. Drug Metab Dispos. 2005 May;33(5):664-71.
• [23] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
• [24] Prediction of cytochrome P450 3A inhibition by verapamil enantiomers and their metabolites. Drug Metab Dispos. 2004 Feb;32(2):259-66.
• [25] Differential expression and function of CYP2C isoforms in human intestine and liver. Pharmacogenetics. 2003 Sep;13(9):565-75.
• [26] Drug interactions with calcium channel blockers: possible involvement of metabolite-intermediate complexation with CYP3A. Drug Metab Dispos. 2000 Feb;28(2):125-30.
• [27] Cytochromes of the P450 2C subfamily are the major enzymes involved in the O-demethylation of verapamil in humans. Naunyn Schmiedebergs Arch Pharmacol. 1995 Dec;353(1):116-21.
• [28] Rapid induction of P-glycoprotein expression by high permeability compounds in colonic cells in vitro: a possible source of transporter mediated drug interactions?. Biochem Pharmacol. 2004 Aug 15;68(4):783-90. doi: 10.1016/j.bcp.2004.05.006.
• [29] 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.
• [30] Mechanism-based inactivation of human cytochrome P4502C8 by drugs in vitro. J Pharmacol Exp Ther. 2004 Dec;311(3):996-1007.
• [31] Inhibition of organic anion transporter (OAT) activity by cigarette smoke condensate. Toxicol In Vitro. 2017 Oct;44:27-35.
• [32] Low doses of BPF-induced hypertrophy in cardiomyocytes derived from human embryonic stem cells via disrupting the mitochondrial fission upon the interaction between ER and calcineurin A-DRP1 signaling pathway. Cell Biol Toxicol. 2022 Jun;38(3):409-426. doi: 10.1007/s10565-021-09615-y. Epub 2021 May 22.
• [33] Screening of a chemical library reveals novel PXR-activating pharmacologic compounds. Toxicol Lett. 2015 Jan 5;232(1):193-202. doi: 10.1016/j.toxlet.2014.10.009. Epub 2014 Oct 16.
• [34] Expression, localization, and function of the carnitine transporter octn2 (slc22a5) in human placenta. Drug Metab Dispos. 2005 Jan;33(1):31-7. doi: 10.1124/dmd.104.001560. Epub 2004 Oct 14.
• [35] Multidrug resistance protein-6 (MRP6) in human dermal fibroblasts. Comparison between cells from normal subjects and from Pseudoxanthoma elasticum patients. Matrix Biol. 2003 Nov;22(6):491-500. doi: 10.1016/j.matbio.2003.09.001.
• [36] Discovery of molecular mechanisms of neuroprotection using cell-based bioassays and oligonucleotide arrays. Physiol Genomics. 2002 Oct 29;11(2):45-52. doi: 10.1152/physiolgenomics.00064.2002.
• [37] Selection of drugs to test the specificity of the Tg.AC assay by screening for induction of the gadd153 promoter in vitro. Toxicol Sci. 2003 Aug;74(2):260-70. doi: 10.1093/toxsci/kfg113. Epub 2003 May 2.
• [38] Plasma atrial natriuretic peptide levels in essential hypertension after treatment with verapamil. Eur J Drug Metab Pharmacokinet. 2002 Jan-Mar;27(1):45-8. doi: 10.1007/BF03190404.
• [39] Verapamil-induced hyperprolactinemia complicated by a pituitary incidentaloma. Ann Pharmacother. 1995 Oct;29(10):999-1001. doi: 10.1177/106002809502901009.
• [40] [Unstable stenocardia: indicators of platelet activity and the effect of verapamil]. Biull Vsesoiuznogo Kardiol Nauchn Tsentra AMN SSSR. 1987;10(2):33-9.
• [41] Protective role of HO-1 for alcohol-dependent liver damage. Dig Dis. 2010;28(6):792-8. doi: 10.1159/000324287. Epub 2011 Apr 27.
• [42] Verapamil potentiates anti-glioblastoma efficacy of temozolomide by modulating apoptotic signaling. Toxicol In Vitro. 2018 Oct;52:306-313. doi: 10.1016/j.tiv.2018.07.001. Epub 2018 Jul 9.
• [43] 8-Methoxypsoralen disrupts MDR3-mediated phospholipids efflux and bile acid homeostasis and its relevance to hepatotoxicity. Toxicology. 2017 Jul 1;386:40-48. doi: 10.1016/j.tox.2017.05.011. Epub 2017 May 24.
• [44] Identification of quaternary ammonium compounds as potent inhibitors of hERG potassium channels. Toxicol Appl Pharmacol. 2011 May 1;252(3):250-8. doi: 10.1016/j.taap.2011.02.016. Epub 2011 Feb 26.
• [45] 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.
• [46] Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis. Chem Res Toxicol. 2015 May 18;28(5):927-34. doi: 10.1021/tx5005248. Epub 2015 Apr 3.
• [47] Glutathione S-transferase M1 and multidrug resistance protein 1 act in synergy to protect melanoma cells from vincristine effects. Mol Pharmacol. 2004 Apr;65(4):897-905. doi: 10.1124/mol.65.4.897.
• [48] Neonicotinoid pesticides poorly interact with human drug transporters. J Biochem Mol Toxicol. 2019 Oct;33(10):e22379. doi: 10.1002/jbt.22379. Epub 2019 Jul 31.
• [49] hKv4.3 channel characterization and regulation by calcium channel antagonists. Biochem Biophys Res Commun. 2001 Feb 23;281(2):452-60. doi: 10.1006/bbrc.2001.4396.
• [50] CACNA1C gene polymorphisms, cardiovascular disease outcomes, and treatment response. Circ Cardiovasc Genet. 2009 Aug;2(4):362-70. doi: 10.1161/CIRCGENETICS.109.857839. Epub 2009 Jun 3.
• [51] 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.
• [52] KCNMB1 genotype influences response to verapamil SR and adverse outcomes in the INternational VErapamil SR/Trandolapril STudy (INVEST). Pharmacogenet Genomics. 2007 Sep;17(9):719-29. doi: 10.1097/FPC.0b013e32810f2e3c.
• [53] A common 1-adrenergic receptor polymorphism predicts favorable response to rate-control therapy in atrial fibrillation. J Am Coll Cardiol. 2012 Jan 3;59(1):49-56. doi: 10.1016/j.jacc.2011.08.061.