General Information of Drug Combination (ID: DCFFJG4)

Drug Combination Name
Testosterone cypionate Theophylline
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Testosterone cypionate   DMC1TEV Theophylline   DMRJFN9
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: 9.01
Bliss Independence Score: 9.01
Loewe Additivity Score: 21.39
LHighest Single Agent (HSA) Score: 21.41

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Testosterone cypionate Interacts with 21 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [4]
Aromatase (CYP19A1) DEQX145 CP19A_HUMAN Metabolism [5]
Cytochrome P450 1A1 (CYP1A1) DE6OQ3W CP1A1_HUMAN Metabolism [6]
Cytochrome P450 4B1 (CYP4B1) DEMF740 CP4B1_HUMAN Metabolism [7]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [8]
Cytochrome P450 3A7 (CYP3A7) DERD86B CP3A7_HUMAN Metabolism [9]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Metabolism [10]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [11]
Cytochrome P450 2B6 (CYP2B6) DEPKLMQ CP2B6_HUMAN Metabolism [12]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [13]
Cytochrome P450 3A43 (CYP3A43) DEO1IE3 CP343_HUMAN Metabolism [14]
Cytochrome P450 1B1 (CYP1B1) DE9QHP6 CP1B1_HUMAN Metabolism [15]
Cholesterol 24-hydroxylase (CYP46A1) DEKP5HX CP46A_HUMAN Metabolism [16]
Cytochrome P450 2A13 (CYP2A13) DEXZA9U CP2AD_HUMAN Metabolism [17]
Steroid 5-alpha-reductase 1 (SRD5A1) DEOG15F S5A1_HUMAN Metabolism [18]
Steroid 5-alpha-reductase 2 (SRD5A2) DEPTJ3D S5A2_HUMAN Metabolism [18]
Steroid 5-alpha-reductase 3 (SRD5A3) DEZGVDW PORED_HUMAN Metabolism [18]
Farnesol dehydrogenase (AKR1B15) DER0XCH AK1BF_HUMAN Metabolism [19]
Dehydrogenase/reductase retSDR3 (HSD17B14) DEGTB1K DHB14_HUMAN Metabolism [20]
Cytochrome P450 MEG (cyp106) DEZ1H4L CPXM_BACME Metabolism [21], [22]
Cytochrome P450 154C2 (cyp154) DEHDW40 A0A345AH95_STRSQ Metabolism [23], [24]
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⏷ Show the Full List of 21 DME(s)
Indication(s) of Theophylline
Disease Entry ICD 11 Status REF
Bronchitis CA20 Approved [2]
Chronic obstructive pulmonary disease CA22 Approved [3]
Lung cancer 2C25.0 Approved [2]
Non-small-cell lung cancer 2C25.Y Approved [2]
Pulmonary disease 1B10-1F85 Approved [2]
Pulmonary emphysema CA21.Z Approved [2]
Severe asthma CA23 Approved [2]
Asthma CA23 Investigative [2]
Theophylline Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Adenosine receptor (ADOR) TTSLI08 NOUNIPROTAC Antagonist [25]
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Theophylline Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Organic anion transporter 2 (SLC22A7) DT0OC1Q S22A7_HUMAN Substrate [26]
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Theophylline Interacts with 6 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [27]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [28]
Cytochrome P450 1A1 (CYP1A1) DE6OQ3W CP1A1_HUMAN Metabolism [29]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [27]
Cytochrome P450 2E1 (CYP2E1) DEVDYN7 CP2E1_HUMAN Metabolism [30]
Cytochrome P450 1B1 (CYP1B1) DE9QHP6 CP1B1_HUMAN Metabolism [31]
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⏷ Show the Full List of 6 DME(s)
Theophylline Interacts with 4 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 2E1 (CYP2E1) OTHQ17JG CP2E1_HUMAN Increases ADR [32]
Renin (REN) OT52GZR2 RENI_HUMAN Increases ADR [32]
Alanine aminotransferase 1 (GPT) OTOXOA0Q ALAT1_HUMAN Increases ADR [32]
Cyclic GMP-AMP phosphodiesterase SMPDL3A (SMPDL3A) OTQDYH8E ASM3A_HUMAN Increases ADR [32]
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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 Theophylline 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: 413).
4 Digging deeper into CYP3A testosterone metabolism: kinetic, regioselectivity, and stereoselectivity differences between CYP3A4/5 and CYP3A7. Drug Metab Dispos. 2017 Dec;45(12):1266-1275.
5 Loss of aromatase cytochrome P450 function as a risk factor for Parkinson's disease? Brain Res Rev. 2008 Mar;57(2):431-43.
6 Allelic variants of human cytochrome P450 1A1 (CYP1A1): effect of T461N and I462V substitutions on steroid hydroxylase specificity. Pharmacogenetics. 2000 Aug;10(6):519-30.
7 Steroid hormone hydroxylase specificities of eleven cDNA-expressed human cytochrome P450s. Arch Biochem Biophys. 1991 Oct;290(1):160-6.
8 In vitro metabolism of midazolam, triazolam, nifedipine, and testosterone by human liver microsomes and recombinant cytochromes p450: role of cyp3a4 and cyp3a5. Drug Metab Dispos. 2003 Jul;31(7):938-44.
9 Steroid hydroxylation by human fetal CYP3A7 and human NADPH-cytochrome P450 reductase coexpressed in insect cells using baculovirus. Res Commun Mol Pathol Pharmacol. 1998 Apr;100(1):15-28.
10 Role of cytochrome P450 2C8 in drug metabolism and interactions. Pharmacol Rev. 2016 Jan;68(1):168-241.
11 Human cytochrome p450 induction and inhibition potential of clevidipine and its primary metabolite h152/81. Drug Metab Dispos. 2006 May;34(5):734-7.
12 Insights into CYP2B6-mediated drug-drug interactions. Acta Pharm Sin B. 2016 Sep;6(5):413-425.
13 Progesterone and testosterone hydroxylation by cytochromes P450 2C19, 2C9, and 3A4 in human liver microsomes. Arch Biochem Biophys. 1997 Oct 1;346(1):161-9.
14 cDNA cloning and initial characterization of CYP3A43, a novel human cytochrome P450. Mol Pharmacol. 2001 Feb;59(2):386-92.
15 Catalytic properties of polymorphic human cytochrome P450 1B1 variants. Carcinogenesis. 1999 Aug;20(8):1607-13.
16 Broad substrate specificity of human cytochrome P450 46A1 which initiates cholesterol degradation in the brain. Biochemistry. 2003 Dec 9;42(48):14284-92.
17 Effects of 8-methoxypsoralen on cytochrome P450 2A13. Carcinogenesis. 2005 Mar;26(3):621-9.
18 Molecular analysis of the SRD5A1 and SRD5A2 genes in patients with benign prostatic hyperplasia with regard to metabolic parameters and selected hormone levels. Int J Environ Res Public Health. 2017 Oct 30;14(11).
19 Aldo-keto Reductase 1B15 (AKR1B15): a mitochondrial human aldo-keto reductase with activity toward steroids and 3-keto-acyl-CoA conjugates. J Biol Chem. 2015 Mar 6;290(10):6531-45.
20 Expression patterns of 17beta-hydroxysteroid dehydrogenase 14 in human tissues. Horm Metab Res. 2012 Dec;44(13):949-56.
21 acillus megaterium SF185 spores exert protective effects against oxidative stress in vivo and in vitro. Sci Rep. 2019 Aug 19;9(1):12082.
22 A Novel NADPH-dependent flavoprotein reductase from Bacillus megaterium acts as an efficient cytochrome P450 reductase. J Biotechnol. 2016 Aug 10;231:83-94.
23 Regio- and stereoselective hydroxylation of testosterone by a novel cytochrome P450 154C2 from Streptomyces avermitilis. Biochem Biophys Res Commun. 2020 Feb 5;522(2):355-361.
24 The metagenome of Caracolus marginella gut microbiome using culture independent approaches and shotgun sequencing. Data Brief. 2017 Nov 22;16:501-505.
25 Emerging adenosine receptor agonists. Expert Opin Emerg Drugs. 2007 Sep;12(3):479-92.
26 Possible involvement of organic anion transporter 2 on the interaction of theophylline with erythromycin in the human liver. Drug Metab Dispos. 2005 May;33(5):619-22.
27 Characterization of human cytochromes P450 involved in theophylline 8-hydroxylation. Biochem Pharmacol. 1995 Jul 17;50(2):205-11.
28 Association between common CYP1A2 polymorphisms and theophylline metabolism in non-smoking healthy volunteers. Basic Clin Pharmacol Toxicol. 2013 Apr;112(4):257-63.
29 Specificity of substrate and inhibitor probes for human cytochromes P450 1A1 and 1A2. J Pharmacol Exp Ther. 1993 Apr;265(1):401-7.
30 Construction and assessment of models of CYP2E1: predictions of metabolism from docking, molecular dynamics, and density functional theoretical calculations. J Med Chem. 2003 Apr 24;46(9):1645-60.
31 Oxidation of xenobiotics by recombinant human cytochrome P450 1B1. Drug Metab Dispos. 1997 May;25(5):617-22.
32 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.