Details of the Drug Combination

General Information of Drug Combination (ID: DCHWH9R)

Drug Combination Name
Arfolitixorin Testosterone cypionate
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Arfolitixorin   DMIXMYK Testosterone cypionate   DMC1TEV
Small molecular drug N.A.
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: KBM-7
Zero Interaction Potency (ZIP) Score: 2.99
Bliss Independence Score: 2.99
Loewe Additivity Score: 5.81
LHighest Single Agent (HSA) Score: 5.86

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Arfolitixorin
Disease Entry ICD 11 Status REF
Colorectal cancer 2B91.Z Phase 3 [2]
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 [3]
Aromatase (CYP19A1) DEQX145 CP19A_HUMAN Metabolism [4]
Cytochrome P450 1A1 (CYP1A1) DE6OQ3W CP1A1_HUMAN Metabolism [5]
Cytochrome P450 4B1 (CYP4B1) DEMF740 CP4B1_HUMAN Metabolism [6]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [7]
Cytochrome P450 3A7 (CYP3A7) DERD86B CP3A7_HUMAN Metabolism [8]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Metabolism [9]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [10]
Cytochrome P450 2B6 (CYP2B6) DEPKLMQ CP2B6_HUMAN Metabolism [11]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [12]
Cytochrome P450 3A43 (CYP3A43) DEO1IE3 CP343_HUMAN Metabolism [13]
Cytochrome P450 1B1 (CYP1B1) DE9QHP6 CP1B1_HUMAN Metabolism [14]
Cholesterol 24-hydroxylase (CYP46A1) DEKP5HX CP46A_HUMAN Metabolism [15]
Cytochrome P450 2A13 (CYP2A13) DEXZA9U CP2AD_HUMAN Metabolism [16]
Steroid 5-alpha-reductase 1 (SRD5A1) DEOG15F S5A1_HUMAN Metabolism [17]
Steroid 5-alpha-reductase 2 (SRD5A2) DEPTJ3D S5A2_HUMAN Metabolism [17]
Steroid 5-alpha-reductase 3 (SRD5A3) DEZGVDW PORED_HUMAN Metabolism [17]
Farnesol dehydrogenase (AKR1B15) DER0XCH AK1BF_HUMAN Metabolism [18]
Dehydrogenase/reductase retSDR3 (HSD17B14) DEGTB1K DHB14_HUMAN Metabolism [19]
Cytochrome P450 MEG (cyp106) DEZ1H4L CPXM_BACME Metabolism [20], [21]
Cytochrome P450 154C2 (cyp154) DEHDW40 A0A345AH95_STRSQ Metabolism [22], [23]
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⏷ Show the Full List of 21 DME(s)

References

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2 ClinicalTrials.gov (NCT03750786) A Study to Compare the Efficacy of Arfolitixorin Versus Leucovorin in Combination With 5 Fluorouracil, Oxaliplatin, and Bevacizumab in Patients With Advanced Colorectal Cancer (AGENT). U.S. National Institutes of Health.
3 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.
4 Loss of aromatase cytochrome P450 function as a risk factor for Parkinson's disease? Brain Res Rev. 2008 Mar;57(2):431-43.
5 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.
6 Steroid hormone hydroxylase specificities of eleven cDNA-expressed human cytochrome P450s. Arch Biochem Biophys. 1991 Oct;290(1):160-6.
7 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.
8 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.
9 Role of cytochrome P450 2C8 in drug metabolism and interactions. Pharmacol Rev. 2016 Jan;68(1):168-241.
10 Human cytochrome p450 induction and inhibition potential of clevidipine and its primary metabolite h152/81. Drug Metab Dispos. 2006 May;34(5):734-7.
11 Insights into CYP2B6-mediated drug-drug interactions. Acta Pharm Sin B. 2016 Sep;6(5):413-425.
12 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.
13 cDNA cloning and initial characterization of CYP3A43, a novel human cytochrome P450. Mol Pharmacol. 2001 Feb;59(2):386-92.
14 Catalytic properties of polymorphic human cytochrome P450 1B1 variants. Carcinogenesis. 1999 Aug;20(8):1607-13.
15 Broad substrate specificity of human cytochrome P450 46A1 which initiates cholesterol degradation in the brain. Biochemistry. 2003 Dec 9;42(48):14284-92.
16 Effects of 8-methoxypsoralen on cytochrome P450 2A13. Carcinogenesis. 2005 Mar;26(3):621-9.
17 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).
18 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.
19 Expression patterns of 17beta-hydroxysteroid dehydrogenase 14 in human tissues. Horm Metab Res. 2012 Dec;44(13):949-56.
20 acillus megaterium SF185 spores exert protective effects against oxidative stress in vivo and in vitro. Sci Rep. 2019 Aug 19;9(1):12082.
21 A Novel NADPH-dependent flavoprotein reductase from Bacillus megaterium acts as an efficient cytochrome P450 reductase. J Biotechnol. 2016 Aug 10;231:83-94.
22 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.
23 The metagenome of Caracolus marginella gut microbiome using culture independent approaches and shotgun sequencing. Data Brief. 2017 Nov 22;16:501-505.