Details of the Drug Combination

General Information of Drug Combination (ID: DCVS3N7)

• Drug Combination Name: Raltegravir + Dantrolene
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Raltegravir (DMYURI6): Small molecular drug
  Dantrolene (DM1D8XY): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 13.78
  Bliss Independence Score: 13.78
  Loewe Additivity Score: 17.65
  LHighest Single Agent (HSA) Score: 17.66

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Raltegravir

Disease Entry	ICD 11	Status	REF
Human immunodeficiency virus infection	1C62	Approved	[2]

Raltegravir Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Human immunodeficiency virus Integrase (HIV IN)	TT5FH9Y	POL_HV1B1	Modulator	[2]

Raltegravir Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[5]
Cytochrome P450 1A1 (CYP1A1)	DE6OQ3W	CP1A1_HUMAN	Metabolism	[6]

Indication(s) of Dantrolene

Disease Entry	ICD 11	Status	REF
Hyperthermia	MG26	Approved	[3]

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] 2007 FDA drug approvals: a year of flux. Nat Rev Drug Discov. 2008 Feb;7(2):107-9.
• [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: 4172).
• [4] Population pharmacokinetic analysis and pharmacogenetics of raltegravir in HIV-positive and healthy individuals. Antimicrob Agents Chemother. 2012 Jun;56(6):2959-66. doi: 10.1128/AAC.05424-11. Epub 2012 Feb 27.
• [5] Successful tacrolimus treatment following renal transplant in a HIV-infected patient with raltegravir previously treated with a protease inhibitor based regimen. Drug Metabol Drug Interact. 2011;26(3):139-41.
• [6] Exposure-related effects of atazanavir on the pharmacokinetics of raltegravir in HIV-1-infected patients. Ther Drug Monit. 2010 Dec;32(6):782-6.
• [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.