General Information of Drug Combination (ID: DC896YR)

Drug Combination Name
Tolazoline Allopurinol
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Tolazoline   DMI40NL Allopurinol   DMLPAOB
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: 57.25
Bliss Independence Score: 57.25
Loewe Additivity Score: 72.82
LHighest Single Agent (HSA) Score: 72.82

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Tolazoline
Disease Entry ICD 11 Status REF
Cerebrovascular disease 8B2Z Approved [2]
Pulmonary hypertension BB01 Approved [3]
Vascular disease BE2Z Investigative [2]
Tolazoline Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Dopamine D2 receptor (D2R) TTEX248 DRD2_HUMAN Antagonist [6]
------------------------------------------------------------------------------------
Indication(s) of Allopurinol
Disease Entry ICD 11 Status REF
Gout FA25 Approved [4]
Hyperuricaemia 5C55.Y Approved [5]
Recurrent adult burkitt lymphoma 2A85.6 Approved [4]
Allopurinol Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Xanthine dehydrogenase/oxidase (XDH) TT7RJY8 XDH_HUMAN Inhibitor [8]
------------------------------------------------------------------------------------
Allopurinol Interacts with 2 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Organic anion transporter 2 (SLC22A7) DT0OC1Q S22A7_HUMAN Substrate [9]
Organic anion transporter 3 (SLC22A8) DTVP67E S22A8_HUMAN Substrate [10]
------------------------------------------------------------------------------------
Allopurinol Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
RNA cytidine acetyltransferase (hALP) DEZV4AP NAT10_HUMAN Metabolism [11]
------------------------------------------------------------------------------------
Allopurinol Interacts with 30 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Solute carrier family 22 member 7 (SLC22A7) OTKTNH1W S22A7_HUMAN Increases Transport [12]
HLA class I histocompatibility antigen, B alpha chain (HLA-B) OTNXFWY2 HLAB_HUMAN Increases Response To Substance [13]
HLA class I histocompatibility antigen, C alpha chain (HLA-C) OTV38BUJ HLAC_HUMAN Increases ADR [14]
HLA class I histocompatibility antigen, A alpha chain (HLA-A) OTAH14LU HLAA_HUMAN Increases ADR [15]
HLA class II histocompatibility antigen, DQ beta 1 chain (HLA-DQB1) OTVVI3UI DQB1_HUMAN Increases ADR [14]
Transmembrane protease serine 2 (TMPRSS2) OTN44YQ5 TMPS2_HUMAN Decreases Expression [16]
Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1) OTY9R6FZ ERN1_HUMAN Increases Expression [17]
Protein c-Fos (FOS) OTJBUVWS FOS_HUMAN Increases Expression [18]
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Increases Expression [19]
Apolipoprotein C-III (APOC3) OTW3520C APOC3_HUMAN Decreases Expression [17]
Apolipoprotein B-100 (APOB) OTH0UOCZ APOB_HUMAN Decreases Expression [17]
Protein disulfide-isomerase (P4HB) OTTYNYPF PDIA1_HUMAN Decreases Expression [17]
Heme oxygenase 1 (HMOX1) OTC1W6UX HMOX1_HUMAN Increases Expression [20]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Expression [20]
Endoplasmic reticulum chaperone BiP (HSPA5) OTFUIRAO BIP_HUMAN Increases Expression [17]
C-C motif chemokine 2 (CCL2) OTAD2HEL CCL2_HUMAN Increases Expression [19]
Platelet glycoprotein 4 (CD36) OT5CZWKY CD36_HUMAN Decreases Expression [17]
Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6) OTAFHAVI ATF6A_HUMAN Increases Expression [17]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Increases Phosphorylation [19]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Increases Phosphorylation [19]
DNA damage-inducible transcript 3 protein (DDIT3) OTI8YKKE DDIT3_HUMAN Increases Expression [17]
Microsomal triglyceride transfer protein large subunit (MTTP) OTNUVSDT MTP_HUMAN Decreases Expression [17]
Cytochrome P450 4A11 (CYP4A11) OTPU5J0S CP4AB_HUMAN Increases Expression [21]
Peroxisome proliferator-activated receptor alpha (PPARA) OTK095PP PPARA_HUMAN Increases Expression [21]
Peroxisomal acyl-coenzyme A oxidase 1 (ACOX1) OTM0A0DY ACOX1_HUMAN Increases Expression [21]
Angiopoietin-related protein 3 (ANGPTL3) OTCD5Z9W ANGL3_HUMAN Decreases Expression [17]
Glycophorin-A (GYPA) OTABU4YV GLPA_HUMAN Increases ADR [22]
Myeloperoxidase (MPO) OTOOXLIN PERM_HUMAN Increases ADR [22]
Intercellular adhesion molecule 1 (ICAM1) OTTOIX77 ICAM1_HUMAN Increases ADR [22]
HLA class I histocompatibility antigen protein P5 (HCP5) OTV0YRI8 HCP5_HUMAN Increases ADR [23]
------------------------------------------------------------------------------------
⏷ Show the Full List of 30 DOT(s)

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 Tolazoline FDA Label
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: 7310).
4 Allopurinol FDA Label
5 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: 6795).
6 Comparative effects of tolazoline and nitroprusside on human isolated radial artery. Ann Thorac Surg. 2006 Jan;81(1):125-31.
7 Uric acid-lowering treatment with benzbromarone in patients with heart failure: a double-blind placebo-controlled crossover preliminary study. Circ Heart Fail. 2010 Jan;3(1):73-81.
8 Allopurinol: xanthine oxidase inhibitor. Tex Med. 1966 Jan;62(1):100-1.
9 Isolation, characterization and differential gene expression of multispecific organic anion transporter 2 in mice. Mol Pharmacol. 2002 Jul;62(1):7-14.
10 Renal transport of organic compounds mediated by mouse organic anion transporter 3 (mOat3): further substrate specificity of mOat3. Drug Metab Dispos. 2004 May;32(5):479-83.
11 Xanthine oxidase inhibition by allopurinol affects the reliability of urinary caffeine metabolic ratios as markers for N-acetyltransferase 2 and CYP1A2 activities. Eur J Clin Pharmacol. 1999 Jan;54(11):869-76.
12 Transport mechanism and substrate specificity of human organic anion transporter 2 (hOat2 [SLC22A7]). J Pharm Pharmacol. 2005 May;57(5):573-8.
13 HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol. Proc Natl Acad Sci U S A. 2005 Mar 15;102(11):4134-9. doi: 10.1073/pnas.0409500102. Epub 2005 Mar 2.
14 A study of HLA class I and class II 4-digit allele level in Stevens-Johnson syndrome and toxic epidermal necrolysis. Int J Immunogenet. 2011 Aug;38(4):303-9. doi: 10.1111/j.1744-313X.2011.01011.x. Epub 2011 May 4.
15 Positive and negative associations of HLA class I alleles with allopurinol-induced SCARs in Koreans. Pharmacogenet Genomics. 2011 May;21(5):303-7. doi: 10.1097/FPC.0b013e32834282b8.
16 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.
17 Drug-induced hepatic steatosis in absence of severe mitochondrial dysfunction in HepaRG cells: proof of multiple mechanism-based toxicity. Cell Biol Toxicol. 2021 Apr;37(2):151-175. doi: 10.1007/s10565-020-09537-1. Epub 2020 Jun 14.
18 Selection of drugs to test the specificity of the Tg.AC assay by screening for induction of the gadd153 promoter in vitro. Toxicol Sci. 2003 Aug;74(2):260-70. doi: 10.1093/toxsci/kfg113. Epub 2003 May 2.
19 Allopurinol induces innate immune responses through mitogen-activated protein kinase signaling pathways in HL-60 cells. J Appl Toxicol. 2016 Sep;36(9):1120-8. doi: 10.1002/jat.3272. Epub 2015 Dec 7.
20 Systemic drugs inducing non-immediate cutaneous adverse reactions and contact sensitizers evoke similar responses in THP-1 cells. J Appl Toxicol. 2015 Apr;35(4):398-406. doi: 10.1002/jat.3033. Epub 2014 Aug 4.
21 Allopurinol Protects Against Cholestatic Liver Injury in Mice Not Through Depletion of Uric Acid. Toxicol Sci. 2021 May 27;181(2):295-305. doi: 10.1093/toxsci/kfab034.
22 ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
23 Clinical Pharmacogenetics Implementation Consortium guidelines for human leukocyte antigen-B genotype and allopurinol dosing. Clin Pharmacol Ther. 2013 Feb;93(2):153-8. doi: 10.1038/clpt.2012.209. Epub 2012 Oct 17.