General Information of Drug Combination (ID: DCX9C16)

Drug Combination Name
Guanfacine Chlorzoxazone
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Guanfacine   DMPN5IH Chlorzoxazone   DMCYVDT
N.A. Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: KBM-7
Zero Interaction Potency (ZIP) Score: 1.2
Bliss Independence Score: 1.2
Loewe Additivity Score: 2.14
LHighest Single Agent (HSA) Score: 2.14

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Guanfacine
Disease Entry ICD 11 Status REF
Attention deficit hyperactivity disorder 6A05.Z Approved [2]
Alzheimer disease 8A20 Phase 3 [3]
Guanfacine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Adrenergic receptor alpha-2A (ADRA2A) TTWG9A4 ADA2A_HUMAN Agonist [5]
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Guanfacine Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [6]
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Indication(s) of Chlorzoxazone
Disease Entry ICD 11 Status REF
Acute pain MG31 Approved [4]
Chlorzoxazone Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Calcium-activated potassium channel (KCN) TTMNI76 NOUNIPROTAC Activator [8]
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Chlorzoxazone Interacts with 6 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [9]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [10]
Cytochrome P450 2A6 (CYP2A6) DEJVYAZ CP2A6_HUMAN Metabolism [11]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [11]
Cytochrome P450 2E1 (CYP2E1) DEVDYN7 CP2E1_HUMAN Metabolism [12]
Cytochrome P450 102A1 (cyp102) DE4OGUF CPXB_BACMB Metabolism [13]
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⏷ Show the Full List of 6 DME(s)
Chlorzoxazone Interacts with 3 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Intermediate conductance calcium-activated potassium channel protein 4 (KCNN4) OTQKQ346 KCNN4_HUMAN Increases Activity [14]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Decreases Activity [15]
Arylamine N-acetyltransferase 2 (NAT2) OTBPDQOY ARY2_HUMAN Affects Metabolism [7]
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References

1 Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
2 Guanfacine FDA Label
3 ClinicalTrials.gov (NCT03116126) Randomised Clinical Trial of Noradrenergic Add-on Therapy With Extended-Release Guanfacine in Alzheimer's Disease. U.S.National Institutes of Health.
4 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: 2322).
5 Scientific rationale for the use of alpha2A-adrenoceptor agonists in treating neuroinflammatory cognitive disorders. Mol Psychiatry. 2023 Apr 7:1-13.
6 An in vitro evaluation of guanfacine as a substrate for P-glycoprotein. Neuropsychiatr Dis Treat. 2011;7:501-5.
7 Effects of cigarette smoking and carbon monoxide on chlorzoxazone and caffeine metabolism. Clin Pharmacol Ther. 2003 Nov;74(5):468-74. doi: 10.1016/j.clpt.2003.07.001.
8 Chlorzoxazone inhibits contraction of rat thoracic aorta. Eur J Pharmacol. 2006 Sep 18;545(2-3):161-6.
9 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
10 Inhibitory monoclonal antibodies to human cytochrome P450 1A2: analysis of phenacetin O-deethylation in human liver. Pharmacogenetics. 1998 Oct;8(5):375-82.
11 Prediction of human liver microsomal oxidations of 7-ethoxycoumarin and chlorzoxazone with kinetic parameters of recombinant cytochrome P-450 enzymes. Drug Metab Dispos. 1999 Nov;27(11):1274-80.
12 Trimethadione metabolism by human liver cytochrome P450: evidence for the involvement of CYP2E1. Xenobiotica. 1998 Nov;28(11):1041-7.
13 Wild-type CYP102A1 as a biocatalyst: turnover of drugs usually metabolised by human liver enzymes. J Biol Inorg Chem. 2007 Mar;12(3):313-23.
14 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.
15 Association of CYP1A1 and CYP1B1 inhibition in in vitro assays with drug-induced liver injury. J Toxicol Sci. 2021;46(4):167-176. doi: 10.2131/jts.46.167.