General Information of Drug Combination (ID: DCTCKIS)

Drug Combination Name
Testosterone cypionate Baclofen
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Testosterone cypionate   DMC1TEV Baclofen   DM0QV1J
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: 6.28
Bliss Independence Score: 6.28
Loewe Additivity Score: 19.28
LHighest Single Agent (HSA) Score: 19.3

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]
------------------------------------------------------------------------------------
⏷ Show the Full List of 21 DME(s)
Indication(s) of Baclofen
Disease Entry ICD 11 Status REF
Multiple sclerosis 8A40 Approved [2]
Fragile X syndrome LD55 Phase 3 [3]
Baclofen Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Gamma-aminobutyric acid B receptor (GABBR) TTDCVZW GABR1_HUMAN; GABR2_HUMAN Modulator [25]
------------------------------------------------------------------------------------
Baclofen Interacts with 3 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Decreases Secretion [26]
Adenosine receptor A1 (ADORA1) OTI7X39E AA1R_HUMAN Increases ADR [27]
ATP-binding cassette sub-family C member 4 (ABCC4) OTO27PAL MRP4_HUMAN Increases Transport [28]
------------------------------------------------------------------------------------

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: 1084).
3 ClinicalTrials.gov (NCT01706523) Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders. U.S. National Institutes of Health.
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 Synthesis and pharmacology of the baclofen homologues 5-amino-4-(4-chlorophenyl)pentanoic acid and the R- and S-enantiomers of 5-amino-3-(4-chlorop... J Med Chem. 1999 Jun 3;42(11):2053-9.
26 Anti-inflammatory effects of the GABA(B) receptor agonist baclofen in allergic contact dermatitis. Exp Dermatol. 2010 Jul 1;19(7):661-6. doi: 10.1111/j.1600-0625.2010.01076.x. Epub 2010 Feb 25.
27 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.
28 Multichannel liquid chromatography-tandem mass spectrometry cocktail method for comprehensive substrate characterization of multidrug resistance-associated protein 4 transporter. Pharm Res. 2007 Dec;24(12):2281-96.