Details of the Drug Combination

General Information of Drug Combination (ID: DC5DKMD)

Drug Combination Name
Guanfacine Dantrolene
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Guanfacine   DMPN5IH Dantrolene   DM1D8XY
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: 6.55
Bliss Independence Score: 6.55
Loewe Additivity Score: 11.27
LHighest Single Agent (HSA) Score: 11.27

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]
------------------------------------------------------------------------------------
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]
------------------------------------------------------------------------------------
Indication(s) of Dantrolene
Disease Entry ICD 11 Status REF
Hyperthermia MG26 Approved [4]
Dantrolene Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Ryanodine receptor (RYR) TT9YXM1 NOUNIPROTAC Modulator [7]
------------------------------------------------------------------------------------
Dantrolene Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [8]
------------------------------------------------------------------------------------
Dantrolene Interacts with 4 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Insulin-like growth factor II (IGF2) OTJ4O6MW IGF2_HUMAN Decreases Response To Substance [9]
Insulin-like growth factor I (IGF1) OTIIZR61 IGF1_HUMAN Decreases Response To Substance [9]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [10]
Angiotensin-converting enzyme 2 (ACE2) OTTRZGU7 ACE2_HUMAN Increases Expression [11]
------------------------------------------------------------------------------------

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: 4172).
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 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
8 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
9 Insulin-like growth factors (IGF) I and II utilize different calcium signaling pathways in a primary human parathyroid cell culture model. World J Surg. 2006 Mar;30(3):333-45. doi: 10.1007/s00268-005-0339-8.
10 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.
11 Effect of common medications on the expression of SARS-CoV-2 entry receptors in liver tissue. Arch Toxicol. 2020 Dec;94(12):4037-4041. doi: 10.1007/s00204-020-02869-1. Epub 2020 Aug 17.