Details of the Drug Combination

General Information of Drug Combination (ID: DCLU9ZB)

Drug Combination Name

Imiquimod Doxycycline

Indication

Disease Entry	Status	REF
Lymphoma, T-Cell, Cutaneous	Phase 1	[1]

Component Drugs

Imiquimod DM1TMA3

Doxycycline DM7ICNU

Small molecular drug

2D MOL

3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)

Indication(s) of Imiquimod

Disease Entry	ICD 11	Status	REF
Alopecia areata	ED70.2	Approved	[2]
Condyloma	1A95	Approved	[2]
Glioblastoma	2A00	Approved	[2]
Melanoma	2C30	Approved	[2]
Skin cancer	2C30-2C37	Approved	[3]

Imiquimod Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Toll-like receptor 7 (TLR7)	TTRJ1K4	TLR7_HUMAN	Agonist	[7]
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Imiquimod Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[8]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[8]
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Imiquimod Interacts with 18 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 1A2 (CYP1A2)	OTLLBX48	CP1A2_HUMAN	Increases Chemical Synthesis	[9]
Transforming growth factor beta-1 proprotein (TGFB1)	OTV5XHVH	TGFB1_HUMAN	Increases Secretion	[10]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Increases Expression	[11]
Interleukin-4 (IL4)	OTOXBWAU	IL4_HUMAN	Increases Secretion	[10]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Increases Secretion	[11]
Fibroblast growth factor 2 (FGF2)	OT7YUJ9F	FGF2_HUMAN	Decreases Expression	[12]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Secretion	[10]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[13]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Increases Secretion	[10]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[13]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[13]
Caspase-1 (CASP1)	OTZ3YQFU	CASP1_HUMAN	Increases Activity	[11]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Increases Phosphorylation	[14]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[15]
Interleukin-2 (IL2)	OTGI4NSA	IL2_HUMAN	Increases Secretion	[10]
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Increases Chemical Synthesis	[9]
Cytochrome P450 2C19 (CYP2C19)	OTFMJYYE	CP2CJ_HUMAN	Increases Metabolism	[9]
Cytochrome P450 2D6 (CYP2D6)	OTZJC802	CP2D6_HUMAN	Increases Metabolism	[9]
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⏷ Show the Full List of 18 DOT(s)

Indication(s) of Doxycycline

Disease Entry	ICD 11	Status	REF
Acne vulgaris	ED80	Approved	[4]
Actinomycosis	N.A.	Approved	[4]
Acute gonococcal cervicitis	N.A.	Approved	[4]
Acute gonococcal epididymo-orchitis	N.A.	Approved	[4]
Advanced gum disease	DA0D	Approved	[5]
Anthrax	1B97	Approved	[4]
Bartonellosis	N.A.	Approved	[4]
Boutonneuse fever	N.A.	Approved	[4]
Brill-Zinsser disease	N.A.	Approved	[4]
Bronchitis	CA20	Approved	[4]
Brucellosis	N.A.	Approved	[4]
Chancroid	N.A.	Approved	[4]
Chlamydiaceae infections	N.A.	Approved	[4]
Chronic periodontitis	DA0C.Y	Approved	[5]
Colorectal carcinoma	N.A.	Approved	[4]
Cutaneous anthrax	N.A.	Approved	[4]
Endemic typhus	N.A.	Approved	[4]
Epidemic louse-borne typhus	N.A.	Approved	[4]
Gastrointestinal anthrax	N.A.	Approved	[4]
Inhalational anthrax	N.A.	Approved	[4]
Listeriosis	N.A.	Approved	[4]
Lymphogranuloma venereum	N.A.	Approved	[4]
Mycoplasma pneumoniae pneumonia	N.A.	Approved	[4]
Ornithosis	N.A.	Approved	[4]
Q fever	N.A.	Approved	[4]
Relapsing fever	N.A.	Approved	[4]
Rickettsialpox	N.A.	Approved	[4]
Rickettsiosis	N.A.	Approved	[4]
Rocky mountain spotted fever	N.A.	Approved	[4]
Syphilis	N.A.	Approved	[4]
Trachoma	N.A.	Approved	[4]
Tularemia	1B94	Approved	[4]
Typhus	N.A.	Approved	[4]
Yaws	N.A.	Approved	[4]
Diabetic foot ulcer	BD54	Phase 2	[6]
Sinusitis	CA0A.Z	Investigative	[4]
Vibrio cholerae infection	1A00	Investigative	[4]

Doxycycline Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Bacterial 30S ribosomal RNA (Bact 30S rRNA)	TTOVFH2	NOUNIPROTAC	Modulator	[17]
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Doxycycline Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[18]
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Doxycycline Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[19]
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Doxycycline Interacts with 9 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Decreases Expression	[20]
Cytochrome P450 1B1 (CYP1B1)	OTYXFLSD	CP1B1_HUMAN	Increases Expression	[16]
Aryl hydrocarbon receptor (AHR)	OTFE4EYE	AHR_HUMAN	Increases Expression	[16]
HLA class I histocompatibility antigen, B alpha chain (HLA-B)	OTNXFWY2	HLAB_HUMAN	Affects Expression	[21]
72 kDa type IV collagenase (MMP2)	OT5NIWA2	MMP2_HUMAN	Decreases Activity	[22]
Stromelysin-1 (MMP3)	OTGBI74Z	MMP3_HUMAN	Decreases Activity	[22]
Neutrophil collagenase (MMP8)	OTZXH19L	MMP8_HUMAN	Decreases Activity	[22]
Collagenase 3 (MMP13)	OTY8BZIE	MMP13_HUMAN	Increases Expression	[23]
TAR DNA-binding protein 43 (TARDBP)	OTVOSFWW	TADBP_HUMAN	Decreases Expression	[24]
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⏷ Show the Full List of 9 DOT(s)

References

1	ClinicalTrials.gov (NCT03116659) CTCL Directed Therapy
2	Imiquimod 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: 5003).
4	Doxycycline 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: 6464).
6	ClinicalTrials.gov (NCT00764361) Safety Study of Topical Doxycycline Gel for Adult Diabetic Lower Extremity Ulcers. U.S. National Institutes of Health.
7	Imiquimod enhances IFN-gamma production and effector function of T cells infiltrating human squamous cell carcinomas of the skin. J Invest Dermatol. 2009 Nov;129(11):2676-85.
8	Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
9	The Toll-like receptor agonist imiquimod is metabolized by aryl hydrocarbon receptor-regulated cytochrome P450 enzymes in human keratinocytes and mouse liver. Arch Toxicol. 2019 Jul;93(7):1917-1926.
10	Cannabidiol selectively modulates interleukin (IL)-1 and IL-6 production in toll-like receptor activated human peripheral blood monocytes. Toxicology. 2021 Dec;464:153016. doi: 10.1016/j.tox.2021.153016. Epub 2021 Nov 2.
11	(9)-Tetrahydrocannabinol Suppresses Monocyte-Mediated Astrocyte Production of Monocyte Chemoattractant Protein 1 and Interleukin-6 in a Toll-Like Receptor 7-Stimulated Human Coculture. J Pharmacol Exp Ther. 2019 Oct;371(1):191-201. doi: 10.1124/jpet.119.260661. Epub 2019 Aug 5.
12	Imiquimod: a potential weapon against Dupuytren contracture. Med Hypotheses. 2006;66(5):991-2. doi: 10.1016/j.mehy.2005.09.052. Epub 2005 Dec 20.
13	Imiquimod induces apoptosis of human melanocytes. Arch Dermatol Res. 2010 May;302(4):301-6. doi: 10.1007/s00403-009-1012-0. Epub 2009 Dec 23.
14	Effect of toll-like receptor 7 and 9 targeted therapy to prevent the development of hepatocellular carcinoma. Liver Int. 2015 Mar;35(3):1063-76. doi: 10.1111/liv.12626. Epub 2014 Jul 30.
15	Tumor-selective induction of apoptosis and the small-molecule immune response modifier imiquimod. J Natl Cancer Inst. 2003 Aug 6;95(15):1138-49. doi: 10.1093/jnci/djg016.
16	Aryl hydrocarbon receptor protects lung adenocarcinoma cells against cigarette sidestream smoke particulates-induced oxidative stress. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):293-301.
17	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
18	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.
19	A further interaction study of quinine with clinically important drugs by human liver microsomes: determinations of inhibition constant (Ki) and type of inhibition. Eur J Drug Metab Pharmacokinet. 1999 Jul-Sep;24(3):272-8.
20	Functional and histochemical analysis of MDR3 P-glycoprotein in a tetracycline-controlled gene expression system. Eur J Med Res. 2000 Dec 29;5(12):517-22.
21	Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis. Chem Res Toxicol. 2015 May 18;28(5):927-34. doi: 10.1021/tx5005248. Epub 2015 Apr 3.
22	Synthesis and in vitro evaluation of targeted tetracycline derivatives: effects on inhibition of matrix metalloproteinases. Bioorg Med Chem. 2007 Mar 15;15(6):2368-74. doi: 10.1016/j.bmc.2007.01.026. Epub 2007 Jan 19.
23	Chloramphenicol causes mitochondrial stress, decreases ATP biosynthesis, induces matrix metalloproteinase-13 expression, and solid-tumor cell invasion. Toxicol Sci. 2010 Jul;116(1):140-50. doi: 10.1093/toxsci/kfq085. Epub 2010 Mar 25.
24	A high-content screen identifies novel compounds that inhibit stress-induced TDP-43 cellular aggregation and associated cytotoxicity. J Biomol Screen. 2014 Jan;19(1):44-56. doi: 10.1177/1087057113501553. Epub 2013 Sep 9.