General Information of Drug Combination (ID: DC41WKW)

Drug Combination Name
Hydroxychloroquine Artemisinin
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Hydroxychloroquine   DMSIVND Artemisinin   DMOY7W3
Small molecular drug 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: 24.82
Bliss Independence Score: 24.82
Loewe Additivity Score: 33.76
LHighest Single Agent (HSA) Score: 33.76

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Hydroxychloroquine
Disease Entry ICD 11 Status REF
Chronic renal failure GB61.Z Approved [2]
Malaria 1F40-1F45 Approved [3]
Plasmodium falciparum malaria 1F40 Approved [2]
Plasmodium malariae malaria N.A. Approved [2]
Plasmodium ovale malaria N.A. Approved [2]
Systemic lupus erythematosus 4A40.0 Approved [2]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 3 [4]
Colon cancer 2B90.Z Investigative [2]
Hydroxychloroquine Interacts with 4 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
HUMAN pH-dependent viral fusion/replication (pH-DVF/R) TTD16BI N.A. Inhibitor [6]
HUMAN glycosylation of host receptor (GHR) TTZGK1R N.A. Inhibitor [6]
Toll-like receptor 7 (TLR7) TTRJ1K4 TLR7_HUMAN Antagonist [7]
HUMAN toll-like receptor 7/9 signalling pathway (TLR7/9 pathway) TT3A1EZ N.A. Inhibitor [8]
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Hydroxychloroquine Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [9]
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Hydroxychloroquine Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [10]
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Hydroxychloroquine Interacts with 30 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 2D6 (CYP2D6) OTZJC802 CP2D6_HUMAN Decreases Activity [11]
Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) OTPGHZB9 IFIT3_HUMAN Increases Expression [12]
CASP8 and FADD-like apoptosis regulator (CFLAR) OTX14BAS CFLAR_HUMAN Decreases Expression [13]
Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1) OTY9R6FZ ERN1_HUMAN Increases Expression [12]
Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1) OT4TMERS NFAC1_HUMAN Affects Expression [14]
Claudin-1 (CLDN1) OT27KV99 CLD1_HUMAN Increases Expression [15]
Interferon beta (IFNB1) OTYQGUB5 IFNB_HUMAN Increases Expression [12]
C-X-C motif chemokine 10 (CXCL10) OTTLQ6S0 CXL10_HUMAN Increases Expression [12]
3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) OTRT3F3U HMDH_HUMAN Affects Expression [16]
Alkaline phosphatase, tissue-nonspecific isozyme (ALPL) OTG7J4BP PPBT_HUMAN Affects Expression [16]
Transcription factor Jun (JUN) OTCYBO6X JUN_HUMAN Increases Phosphorylation [12]
Cathepsin B (CTSB) OTP9G5QB CATB_HUMAN Affects Localization [17]
72 kDa type IV collagenase (MMP2) OT5NIWA2 MMP2_HUMAN Decreases Expression [18]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Expression [19]
C-C motif chemokine 2 (CCL2) OTAD2HEL CCL2_HUMAN Increases Expression [19]
NF-kappa-B inhibitor alpha (NFKBIA) OTFT924M IKBA_HUMAN Increases Degradation [12]
CD40 ligand (CD40LG) OT75Z6A6 CD40L_HUMAN Decreases Expression [14]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [13]
Transcription factor p65 (RELA) OTUJP9CN TF65_HUMAN Increases Expression [12]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Activity [17]
TNF receptor-associated factor 3 (TRAF3) OT5TQBGV TRAF3_HUMAN Increases Expression [12]
Nuclear factor of activated T-cells, cytoplasmic 2 (NFATC2) OTK5T6HZ NFAC2_HUMAN Affects Localization [14]
Sequestosome-1 (SQSTM1) OTGY5D5J SQSTM_HUMAN Increases Expression [20]
Interferon regulatory factor 3 (IRF3) OT81U8ME IRF3_HUMAN Increases Phosphorylation [12]
Occludin (OCLN) OTSUTVWL OCLN_HUMAN Increases Expression [15]
Mitochondrial antiviral-signaling protein (MAVS) OTTQ0J64 MAVS_HUMAN Increases Expression [12]
S-adenosylmethionine-dependent nucleotide dehydratase RSAD2 (RSAD2) OTCA9WCM RSAD2_HUMAN Increases Expression [12]
Interferon-induced helicase C domain-containing protein 1 (IFIH1) OTZA2AHA IFIH1_HUMAN Increases Expression [12]
Toll-like receptor 9 (TLR9) OTFZ45HX TLR9_HUMAN Decreases Expression [21]
7-dehydrocholesterol reductase (DHCR7) OTLILBUI DHCR7_HUMAN Affects Expression [16]
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⏷ Show the Full List of 30 DOT(s)
Indication(s) of Artemisinin
Disease Entry ICD 11 Status REF
Malaria 1F40-1F45 Approved [5]
Artemisinin Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Plasmodium Dihydroorotate dehydrogenase (Malaria DHOdehase) TT3PQ2Y PYRD_PLAF7 Inhibitor [5]
Sarcoplasmic/endoplasmic reticulum calcium ATPase (ATP2A) TTZVSJ2 NOUNIPROTAC Inhibitor [5]
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Artemisinin Interacts with 4 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [22]
Cytochrome P450 2A6 (CYP2A6) DEJVYAZ CP2A6_HUMAN Metabolism [23]
Glutathione S-transferase alpha-1 (GSTA1) DE4ZHS1 GSTA1_HUMAN Metabolism [24]
Cytochrome P450 2B6 (CYP2B6) DEPKLMQ CP2B6_HUMAN Metabolism [22]
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Artemisinin Interacts with 10 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Glutathione S-transferase A1 (GSTA1) OTA7K5XA GSTA1_HUMAN Decreases Activity [24]
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Increases Expression [25]
Cytochrome P450 2B6 (CYP2B6) OTOYO4S7 CP2B6_HUMAN Increases Expression [25]
Cytochrome P450 1A2 (CYP1A2) OTLLBX48 CP1A2_HUMAN Decreases Activity [26]
Cytochrome P450 2C19 (CYP2C19) OTFMJYYE CP2CJ_HUMAN Decreases Activity [26]
Glutathione S-transferase P (GSTP1) OTLP0A0Y GSTP1_HUMAN Decreases Activity [24]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Expression [25]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Activity [27]
Isocitrate dehydrogenase subunit alpha, mitochondrial (IDH3A) OT5QQB5L IDH3A_HUMAN Decreases Expression [27]
Nuclear receptor subfamily 1 group I member 3 (NR1I3) OTS3SGH7 NR1I3_HUMAN Increases Activity [28]
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⏷ Show the Full List of 10 DOT(s)

References

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2 Hydroxychloroquine 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: 7198).
4 ClinicalTrials.gov (NCT04341727) Hydroxychloroquine,Hydroxychloroquine,Azithromycin in the Treatment of SARS CoV-2 Infection (WU352). U.S. National Institutes of Health.
5 The fight against drug-resistant malaria: novel plasmodial targets and antimalarial drugs. Curr Med Chem. 2008;15(2):161-71.
6 Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020 Mar;30(3):269-271.
7 TLR7/9 antagonists as therapeutics for immune-mediated inflammatory disorders. Inflamm Allergy Drug Targets. 2007 Dec;6(4):223-35.
8 Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology. Nat Rev Rheumatol. 2020 Mar;16(3):155-166.
9 MDR-ABC transporters: biomarkers in rheumatoid arthritis. Clin Exp Rheumatol. 2013 Sep-Oct;31(5):779-87.
10 Hydroxychloroquine: a physiologically-based pharmacokinetic model in the context of cancer-related autophagy modulation. J Pharmacol Exp Ther. 2018 Jun;365(3):447-459.
11 Somer M, Kallio J, Pesonen U, Pyykko K, Huupponen R, Scheinin M "Influence of hydroxychloroquine on the bioavailability of oral metoprolol." Br J Clin Pharmacol 49 (2000): 549-54. [PMID: 10848718]
12 Hydroxychloroquine-inhibited dengue virus is associated with host defense machinery. J Interferon Cytokine Res. 2015 Mar;35(3):143-56. doi: 10.1089/jir.2014.0038. Epub 2014 Oct 16.
13 Hydroxychloroquine potentiates Fas-mediated apoptosis of rheumatoid synoviocytes. Clin Exp Immunol. 2006 Jun;144(3):503-11. doi: 10.1111/j.1365-2249.2006.03070.x.
14 Hydroxychloroquine inhibits CD154 expression in CD4(+) T lymphocytes of systemic lupus erythematosus through NFAT, but not STAT5, signaling. Arthritis Res Ther. 2017 Aug 9;19(1):183. doi: 10.1186/s13075-017-1393-y.
15 Chloroquine and Hydroxychloroquine Increase Retinal Pigment Epithelial Layer Permeability. J Biochem Mol Toxicol. 2015 Jul;29(7):299-304. doi: 10.1002/jbt.21696. Epub 2015 Mar 9.
16 Hydroxychloroquine decreases human MSC-derived osteoblast differentiation and mineralization in vitro. J Cell Mol Med. 2018 Feb;22(2):873-882. doi: 10.1111/jcmm.13373. Epub 2017 Oct 3.
17 Mitochondrial membrane permeabilization is a critical step of lysosome-initiated apoptosis induced by hydroxychloroquine. Oncogene. 2003 Jun 19;22(25):3927-36. doi: 10.1038/sj.onc.1206622.
18 Attenuation of chloroquine and hydroxychloroquine on the invasive potential of bladder cancer through targeting matrix metalloproteinase 2 expression. Environ Toxicol. 2021 Nov;36(11):2138-2145. doi: 10.1002/tox.23328. Epub 2021 Jul 19.
19 Reactive oxygen species mediate chloroquine-induced expression of chemokines by human astroglial cells. Glia. 2004 Jul;47(1):9-20. doi: 10.1002/glia.20017.
20 d-galactose induces premature senescence of lens epithelial cells by disturbing autophagy flux and mitochondrial functions. Toxicol Lett. 2018 Jun 1;289:99-106. doi: 10.1016/j.toxlet.2018.02.001. Epub 2018 Feb 6.
21 Antagonist-mediated down-regulation of Toll-like receptors increases the prevalence of human papillomavirus infection in systemic lupus erythematosus. Arthritis Res Ther. 2012 Apr 18;14(2):R80. doi: 10.1186/ar3803.
22 Antimalarial artemisinin drugs induce cytochrome P450 and MDR1 expression by activation of xenosensors pregnane X receptor and constitutive androstane receptor. Mol Pharmacol. 2005 Jun;67(6):1954-65.
23 Identification of the human cytochrome P450 enzymes involved in the in vitro metabolism of artemisinin. Br J Clin Pharmacol. 1999 Oct;48(4):528-35.
24 Inhibition of glutathione S-transferases by antimalarial drugs possible implications for circumventing anticancer drug resistance. Int J Cancer. 2002 Feb 10;97(5):700-5.
25 Antimalarial artemisinin drugs induce cytochrome P450 and MDR1 expression by activation of xenosensors pregnane X receptor and constitutive androstane receptor. Mol Pharmacol. 2005 Jun;67(6):1954-65.
26 Application of higher throughput screening (HTS) inhibition assays to evaluate the interaction of antiparasitic drugs with cytochrome P450s. Drug Metab Dispos. 2001 Jan;29(1):30-5.
27 Identification of Compounds That Inhibit Estrogen-Related Receptor Alpha Signaling Using High-Throughput Screening Assays. Molecules. 2019 Feb 27;24(5):841. doi: 10.3390/molecules24050841.
28 In vivo and mechanistic evidence of nuclear receptor CAR induction by artemisinin. Eur J Clin Invest. 2006 Sep;36(9):647-53. doi: 10.1111/j.1365-2362.2006.01700.x.