Details of the Drug Combination

General Information of Drug Combination (ID: DCOZBC7)

• Drug Combination Name: Doxapram + Isosorbide Dinitrate
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Doxapram (DMCYANK): Small molecular drug
  Isosorbide Dinitrate (DMBI4JG): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 12.12
  Bliss Independence Score: 12.12
  Loewe Additivity Score: 25.76
  LHighest Single Agent (HSA) Score: 25.77

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Doxapram

Disease Entry	ICD 11	Status	REF
Respiratory disease	CB40	Approved	[2]

Doxapram Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Peripheral carotid chemoreceptor (PCC)	TT6EYVN	NOUNIPROTAC	Stimulator	[5]

Doxapram Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[6]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[6]

Doxapram Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Prolactin (PRL)	OTWFQGX7	PRL_HUMAN	Increases Expression	[7]

Indication(s) of Isosorbide Dinitrate

Disease Entry	ICD 11	Status	REF
Anal fissure	DB50.0	Approved	[3]
Angina pectoris	BA40	Approved	[3]
Chronic heart failure	BD1Z	Approved	[4]

Isosorbide Dinitrate Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Guanylate cyclase (GC)	TT6HPVC	NOUNIPROTAC	Stimulator	[8]

Isosorbide Dinitrate Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[9]
Glutathione S-transferase alpha-1 (GSTA1)	DE4ZHS1	GSTA1_HUMAN	Metabolism	[10]

Isosorbide Dinitrate Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Decreases Activity	[11]
Glucose-6-phosphate 1-dehydrogenase (G6PD)	OT300SMK	G6PD_HUMAN	Decreases Response To Substance	[12]

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] 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: 7169).
• [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: 7051).
• [4] Isosorbide dinitrate FDA Label
• [5] Ovalbumin sensitization alters the ventilatory responses to chemical challenges in guinea pigs. J Appl Physiol (1985). 2005 Nov;99(5):1782-8.
• [6] Population pharmacokinetics of doxapram in low-birth-weight Japanese infants with apnea. Eur J Pediatr. 2015 Apr;174(4):509-18.
• [7] Doxapram-induced panic attacks and cortisol elevation. Psychiatry Res. 2005 Feb 28;133(2-3):253-61. doi: 10.1016/j.psychres.2004.10.010.
• [8] Nitric oxide and nitric oxide synthase isoforms in the normal, hypertrophic, and failing heart. Mol Cell Biochem. 2010 Jan;333(1-2):191-201.
• [9] Isoforms of cytochrome P450 on organic nitrate-derived nitric oxide release in human heart vessels. FEBS Lett. 1999 Jun 11;452(3):165-9.
• [10] Nitroglycerin and isosorbide dinitrate stimulation of glutathione disulfide efflux from perfused rat liver. Biochem Pharmacol. 1989 Nov 1;38(21):3807-10.
• [11] 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.
• [12] Isosorbide dinitrate-induced hemolysis in G6PD-deficient subjects. Acta Haematol. 1983;69(1):63-4. doi: 10.1159/000206844.