Details of the Drug Combination

General Information of Drug Combination (ID: DCXRQUG)

• Drug Combination Name: Allopurinol + Rifampin
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Allopurinol (DMLPAOB): Small molecular drug
  Rifampin (DMA8J1G): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 31.71
  Bliss Independence Score: 31.71
  Loewe Additivity Score: 49.08
  LHighest Single Agent (HSA) Score: 49.08

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Allopurinol

Disease Entry	ICD 11	Status	REF
Gout	FA25	Approved	[2]
Hyperuricaemia	5C55.Y	Approved	[3]
Recurrent adult burkitt lymphoma	2A85.6	Approved	[2]

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	[6]

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	[7]
Organic anion transporter 3 (SLC22A8)	DTVP67E	S22A8_HUMAN	Substrate	[8]

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	[9]

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	[10]
HLA class I histocompatibility antigen, B alpha chain (HLA-B)	OTNXFWY2	HLAB_HUMAN	Increases Response To Substance	[11]
HLA class I histocompatibility antigen, C alpha chain (HLA-C)	OTV38BUJ	HLAC_HUMAN	Increases ADR	[12]
HLA class I histocompatibility antigen, A alpha chain (HLA-A)	OTAH14LU	HLAA_HUMAN	Increases ADR	[13]
HLA class II histocompatibility antigen, DQ beta 1 chain (HLA-DQB1)	OTVVI3UI	DQB1_HUMAN	Increases ADR	[12]
Transmembrane protease serine 2 (TMPRSS2)	OTN44YQ5	TMPS2_HUMAN	Decreases Expression	[14]
Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1)	OTY9R6FZ	ERN1_HUMAN	Increases Expression	[15]
Protein c-Fos (FOS)	OTJBUVWS	FOS_HUMAN	Increases Expression	[16]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Increases Expression	[17]
Apolipoprotein C-III (APOC3)	OTW3520C	APOC3_HUMAN	Decreases Expression	[15]
Apolipoprotein B-100 (APOB)	OTH0UOCZ	APOB_HUMAN	Decreases Expression	[15]
Protein disulfide-isomerase (P4HB)	OTTYNYPF	PDIA1_HUMAN	Decreases Expression	[15]
Heme oxygenase 1 (HMOX1)	OTC1W6UX	HMOX1_HUMAN	Increases Expression	[18]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[18]
Endoplasmic reticulum chaperone BiP (HSPA5)	OTFUIRAO	BIP_HUMAN	Increases Expression	[15]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Increases Expression	[17]
Platelet glycoprotein 4 (CD36)	OT5CZWKY	CD36_HUMAN	Decreases Expression	[15]
Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6)	OTAFHAVI	ATF6A_HUMAN	Increases Expression	[15]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Increases Phosphorylation	[17]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Increases Phosphorylation	[17]
DNA damage-inducible transcript 3 protein (DDIT3)	OTI8YKKE	DDIT3_HUMAN	Increases Expression	[15]
Microsomal triglyceride transfer protein large subunit (MTTP)	OTNUVSDT	MTP_HUMAN	Decreases Expression	[15]
Cytochrome P450 4A11 (CYP4A11)	OTPU5J0S	CP4AB_HUMAN	Increases Expression	[19]
Peroxisome proliferator-activated receptor alpha (PPARA)	OTK095PP	PPARA_HUMAN	Increases Expression	[19]
Peroxisomal acyl-coenzyme A oxidase 1 (ACOX1)	OTM0A0DY	ACOX1_HUMAN	Increases Expression	[19]
Angiopoietin-related protein 3 (ANGPTL3)	OTCD5Z9W	ANGL3_HUMAN	Decreases Expression	[15]
Glycophorin-A (GYPA)	OTABU4YV	GLPA_HUMAN	Increases ADR	[20]
Myeloperoxidase (MPO)	OTOOXLIN	PERM_HUMAN	Increases ADR	[20]
Intercellular adhesion molecule 1 (ICAM1)	OTTOIX77	ICAM1_HUMAN	Increases ADR	[20]
HLA class I histocompatibility antigen protein P5 (HCP5)	OTV0YRI8	HCP5_HUMAN	Increases ADR	[21]

Indication(s) of Rifampin

Disease Entry	ICD 11	Status	REF
Tuberculosis	1B10-1B1Z	Approved	[4]

Rifampin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Bacterial RNA polymerase switch region (Bact RNAP-SR)	TTIJ5EB	NOUNIPROTAC	Inhibitor	[22]

Rifampin Interacts with 5 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 2 (ABCC2)	DTFI42L	MRP2_HUMAN	Substrate	[23]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[24]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[25]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[26]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[27]

References

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• [2] Allopurinol FDA Label
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• [17] 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.
• [18] 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.
• [19] 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.
• [20] 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.
• [21] 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.
• [22] Bacillus subtilis tolerance of moderate concentrations of rifampin involves the sigma(B)-dependent general and multiple stress response. J Bacteriol. 2002 Jan;184(2):459-67.
• [23] Expression and distribution of CYP3A genes, CYP2B22, and MDR1, MRP1, MRP2, LRP efflux transporters in brain of control and rifampicin-treated pigs. Mol Cell Biochem. 2010 Apr;337(1-2):133-43.
• [24] Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
• [25] Arginine-482 is not essential for transport of antibiotics, primary bile acids and unconjugated sterols by the human breast cancer resistance protein (ABCG2). Biochem J. 2005 Jan 15;385(Pt 2):419-26.
• [26] Human organic anion transporting polypeptide-C (SLC21A6) is a major determinant of rifampin-mediated pregnane X receptor activation. J Pharmacol Exp Ther. 2003 Jan;304(1):223-8.
• [27] Interactions of rifamycin SV and rifampicin with organic anion uptake systems of human liver. Hepatology. 2002 Jul;36(1):164-72.