General Information of Drug Combination (ID: DC9OWVN)

Drug Combination Name
PF-02545920 Isosorbide Dinitrate
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs PF-02545920   DMJPE61 Isosorbide Dinitrate   DMBI4JG
Small molecular drug 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: 8.83
Bliss Independence Score: 8.83
Loewe Additivity Score: 15.15
LHighest Single Agent (HSA) Score: 15.18

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of PF-02545920
Disease Entry ICD 11 Status REF
Huntington disease 8A01.10 Phase 2 [2]
Schizophrenia 6A20 Phase 2 [3]
PF-02545920 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Phosphodiesterase 10A (PDE10) TTJW4LU PDE10_HUMAN Inhibitor [2]
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PF-02545920 Interacts with 3 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Lipid transferase CIDEA (CIDEA) OTDUTSOV CIDEA_HUMAN Increases Expression [6]
Type II iodothyronine deiodinase (DIO2) OTGPNSLH IOD2_HUMAN Increases Expression [6]
Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A) OTHCDQ22 PRGC1_HUMAN Increases Expression [6]
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Indication(s) of Isosorbide Dinitrate
Disease Entry ICD 11 Status REF
Anal fissure DB50.0 Approved [4]
Angina pectoris BA40 Approved [4]
Chronic heart failure BD1Z Approved [5]
Isosorbide Dinitrate Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Guanylate cyclase (GC) TT6HPVC NOUNIPROTAC Stimulator [7]
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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 [8]
Glutathione S-transferase alpha-1 (GSTA1) DE4ZHS1 GSTA1_HUMAN Metabolism [9]
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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 [10]
Glucose-6-phosphate 1-dehydrogenase (G6PD) OT300SMK G6PD_HUMAN Decreases Response To Substance [11]
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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 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
3 ClinicalTrials.gov (NCT01939548) An Outpatient Study Of The Efficacy, Safety, And Tolerability Of PF-02545920 In The Adjunctive Treatment Of Sub-Optimally Controlled Symptoms of Schizophrenia. 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: 7051).
5 Isosorbide dinitrate FDA Label
6 A novel thermoregulatory role for PDE10A in mouse and human adipocytes. EMBO Mol Med. 2016 Jul 1;8(7):796-812. doi: 10.15252/emmm.201506085. Print 2016 Jul.
7 Nitric oxide and nitric oxide synthase isoforms in the normal, hypertrophic, and failing heart. Mol Cell Biochem. 2010 Jan;333(1-2):191-201.
8 Isoforms of cytochrome P450 on organic nitrate-derived nitric oxide release in human heart vessels. FEBS Lett. 1999 Jun 11;452(3):165-9.
9 Nitroglycerin and isosorbide dinitrate stimulation of glutathione disulfide efflux from perfused rat liver. Biochem Pharmacol. 1989 Nov 1;38(21):3807-10.
10 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.
11 Isosorbide dinitrate-induced hemolysis in G6PD-deficient subjects. Acta Haematol. 1983;69(1):63-4. doi: 10.1159/000206844.