Details of the Drug Combination

General Information of Drug Combination (ID: DCJDKVE)

Drug Combination Name
Amodiaquine Artesunate
Indication
Disease Entry Status REF
HIV Infections Phase 1 [1]
Component Drugs Amodiaquine   DME4RA8 Artesunate   DMR27C8
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Amodiaquine
Disease Entry ICD 11 Status REF
Malaria 1F40-1F45 Approved [2]
Middle East Respiratory Syndrome (MERS) 1D64 Preclinical [3]
Severe acute respiratory syndrome (SARS) 1D65 Preclinical [3]
Amodiaquine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Histamine N-methyltransferase (HNMT) TT2B6EV HNMT_HUMAN Inhibitor [6]
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Amodiaquine Interacts with 5 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 1A1 (CYP1A1) DE6OQ3W CP1A1_HUMAN Metabolism [7]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Metabolism [8]
Cytochrome P450 1B1 (CYP1B1) DE9QHP6 CP1B1_HUMAN Metabolism [7]
Glutathione S-transferase mu-4 (GSTM4) DERQ52Z GSTM4_HUMAN Metabolism [9]
Cytochrome P450 102A1 (cyp102) DE4OGUF CPXB_BACMB Metabolism [10]
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Amodiaquine Interacts with 34 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Increases Activity [11]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Decreases Response To Substance [12]
Cytochrome P450 1A2 (CYP1A2) OTLLBX48 CP1A2_HUMAN Decreases Activity [13]
Cytochrome P450 2C9 (CYP2C9) OTGLBN29 CP2C9_HUMAN Decreases Activity [13]
Cytochrome P450 2C19 (CYP2C19) OTFMJYYE CP2CJ_HUMAN Decreases Activity [13]
Proepiregulin (EREG) OTRM4NQY EREG_HUMAN Increases Expression [14]
Interleukin-1 alpha (IL1A) OTPSGILV IL1A_HUMAN Decreases Expression [14]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Activity [15]
Retinoblastoma-associated protein (RB1) OTQJUJMZ RB_HUMAN Affects Phosphorylation [16]
Cathepsin D (CTSD) OTQZ36F3 CATD_HUMAN Decreases Activity [16]
Procathepsin L (CTSL) OTYTUW29 CATL1_HUMAN Decreases Activity [16]
Cathepsin B (CTSB) OTP9G5QB CATB_HUMAN Decreases Activity [16]
Hepatocyte growth factor receptor (MET) OT7K55MU MET_HUMAN Increases Expression [14]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [12]
Bone morphogenetic protein 6 (BMP6) OT9WN536 BMP6_HUMAN Increases Expression [14]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Affects Expression [16]
Prostaglandin G/H synthase 2 (PTGS2) OT75U9M4 PGH2_HUMAN Decreases Expression [14]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Affects Expression [16]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Cleavage [12]
Tumor necrosis factor-inducible gene 6 protein (TNFAIP6) OT1SLUZH TSG6_HUMAN Decreases Expression [14]
Transcription factor E2F1 (E2F1) OTLKYBBC E2F1_HUMAN Affects Expression [16]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [12]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Decreases Expression [12]
PTB-containing, cubilin and LRP1-interacting protein (PID1) OT5YJ7FI PCLI1_HUMAN Increases Expression [14]
Cytochrome P450 2A6 (CYP2A6) OT52TWG3 CP2A6_HUMAN Increases Metabolism [12]
Cytochrome P450 2E1 (CYP2E1) OTHQ17JG CP2E1_HUMAN Increases Metabolism [12]
Myeloperoxidase (MPO) OTOOXLIN PERM_HUMAN Increases ADR [17]
Cytochrome P450 2B6 (CYP2B6) OTOYO4S7 CP2B6_HUMAN Increases Metabolism [12]
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Increases Metabolism [9]
Cytochrome P450 3A5 (CYP3A5) OTSXFBXB CP3A5_HUMAN Increases Metabolism [12]
Cytochrome P450 3A7 (CYP3A7) OTTCDHHM CP3A7_HUMAN Increases Metabolism [12]
Cytochrome P450 2A13 (CYP2A13) OTVUDLT3 CP2AD_HUMAN Increases Metabolism [12]
Cytochrome P450 2C18 (CYP2C18) OTY687L9 CP2CI_HUMAN Increases Metabolism [12]
Cytochrome P450 2D6 (CYP2D6) OTZJC802 CP2D6_HUMAN Increases Metabolism [9]
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⏷ Show the Full List of 34 DOT(s)
Indication(s) of Artesunate
Disease Entry ICD 11 Status REF
Infection of P. falciparum 1F40 Approved [4]
Malaria 1F40-1F45 Approved [5]
Plasmodium falciparum malaria 1F40 Approved [4]
Artesunate Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Sarcoplasmic/endoplasmic reticulum calcium ATPase (ATP2A) TTZVSJ2 NOUNIPROTAC Inhibitor [5]
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Artesunate Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 2A6 (CYP2A6) DEJVYAZ CP2A6_HUMAN Metabolism [21]
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Artesunate Interacts with 57 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Catalase (CAT) OTHEBX9R CATA_HUMAN Increases Expression [18]
Transcription factor Sp1 (SP1) OTISPT4X SP1_HUMAN Decreases Expression [18]
Glutathione S-transferase P (GSTP1) OTLP0A0Y GSTP1_HUMAN Decreases Expression [18]
Tumor necrosis factor receptor superfamily member 6 (FAS) OTP9XG86 TNR6_HUMAN Increases Expression [18]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [18]
Serine/threonine-protein kinase Chk1 (CHEK1) OTTTI622 CHK1_HUMAN Increases Phosphorylation [22]
Ubiquitin-like protein ATG12 (ATG12) OTJRO09Y ATG12_HUMAN Increases Expression [23]
Apoptosis-inducing factor 1, mitochondrial (AIFM1) OTKPWB7Q AIFM1_HUMAN Affects Localization [24]
Serine/threonine-protein kinase Chk2 (CHEK2) OT8ZPCNS CHK2_HUMAN Increases Phosphorylation [22]
Metalloproteinase inhibitor 1 (TIMP1) OTOXC51H TIMP1_HUMAN Increases Expression [23]
Fibronectin (FN1) OTB5ZN4Q FINC_HUMAN Decreases Expression [23]
Ferritin heavy chain (FTH1) OT6IFS0O FRIH_HUMAN Decreases Expression [23]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Expression [25]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [24]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [24]
Matrix metalloproteinase-9 (MMP9) OTB2QDAV MMP9_HUMAN Decreases Expression [23]
Replication protein A 32 kDa subunit (RPA2) OTZ54WAF RFA2_HUMAN Increases Phosphorylation [22]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Phosphorylation [22]
Desmin (DES) OTI09KBW DESM_HUMAN Decreases Expression [23]
Phospholipid hydroperoxide glutathione peroxidase GPX4 (GPX4) OTRAFFX2 GPX4_HUMAN Decreases Activity [23]
Serine/threonine-protein kinase mTOR (MTOR) OTHH8KU7 MTOR_HUMAN Decreases Phosphorylation [19]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Affects Expression [24]
Actin, aortic smooth muscle (ACTA2) OTEDLG8E ACTA_HUMAN Decreases Expression [23]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [24]
Sequestosome-1 (SQSTM1) OTGY5D5J SQSTM_HUMAN Decreases Expression [23]
Nuclear receptor coactivator 4 (NCOA4) OTRVU0UA NCOA4_HUMAN Decreases Expression [23]
Nuclear factor erythroid 2-related factor 2 (NFE2L2) OT0HENJ5 NF2L2_HUMAN Affects Localization [26]
Microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B) OTUYHB84 MLP3B_HUMAN Increases Lipidation [19]
Autophagy protein 5 (ATG5) OT4T5SMS ATG5_HUMAN Increases Expression [23]
DNA dC->dU-editing enzyme APOBEC-3C (APOBEC3C) OTPL0AI1 ABC3C_HUMAN Increases Expression [22]
Ubiquitin-like-conjugating enzyme ATG3 (ATG3) OT28VBVK ATG3_HUMAN Increases Expression [23]
Small ribosomal subunit protein uS8 (RPS15A) OT0BUA12 RS15A_HUMAN Decreases Response To Substance [20]
Mitochondrial thiamine pyrophosphate carrier (SLC25A19) OT157TY3 TPC_HUMAN Decreases Response To Substance [20]
Atypical kinase COQ8A, mitochondrial (COQ8A) OT1ETSA2 COQ8A_HUMAN Decreases Response To Substance [20]
Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial (MTHFD2) OT1LQSGX MTDC_HUMAN Decreases Response To Substance [20]
Large ribosomal subunit protein uL30 (RPL7) OT4WCQBE RL7_HUMAN Decreases Response To Substance [20]
Glutamate--cysteine ligase regulatory subunit (GCLM) OT6CP234 GSH0_HUMAN Decreases Response To Substance [27]
Integrin beta-1 (ITGB1) OT6G1IAR ITB1_HUMAN Increases Response To Substance [20]
CAP-Gly domain-containing linker protein 4 (CLIP4) OT75KVQK CLIP4_HUMAN Increases Response To Substance [20]
Glutathione S-transferase theta-2 (GSTT2) OTANW3TJ GST2_HUMAN Affects Response To Substance [27]
ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 2 (BST1) OTAV5SE7 BST1_HUMAN Increases Response To Substance [20]
Small ribosomal subunit protein eS12 (RPS12) OTBRQ8MS RS12_HUMAN Decreases Response To Substance [20]
Dopamine beta-hydroxylase (DBH) OTC6I2SP DOPO_HUMAN Increases Response To Substance [20]
Glutamate--cysteine ligase catalytic subunit (GCLC) OTESDI4D GSH1_HUMAN Decreases Response To Substance [27]
Nck-associated protein 1 (NCKAP1) OTEZQXXJ NCKP1_HUMAN Increases Response To Substance [20]
Small ribosomal subunit protein eS32 (RPL41) OTFW5IFO RS32_HUMAN Decreases Response To Substance [20]
Translationally-controlled tumor protein (TPT1) OTHMTRJU TCTP_HUMAN Affects Response To Substance [28]
Nascent polypeptide-associated complex subunit alpha (NACA) OTLP1KR3 NACA_HUMAN Decreases Response To Substance [20]
Glutathione S-transferase Mu 4 (GSTM4) OTOTF8DU GSTM4_HUMAN Affects Response To Substance [27]
Maleylacetoacetate isomerase (GSTZ1) OTQ43JCE MAAI_HUMAN Affects Response To Substance [27]
Large ribosomal subunit protein eL6 (RPL6) OTRU71O4 RL6_HUMAN Decreases Response To Substance [20]
Small ribosomal subunit protein eS6 (RPS6) OTT4D1LN RS6_HUMAN Decreases Response To Substance [20]
Frizzled-7 (FZD7) OTTK3F6E FZD7_HUMAN Increases Response To Substance [20]
Serine/arginine-rich splicing factor 2 (SRSF2) OTVDHO6U SRSF2_HUMAN Decreases Response To Substance [20]
T-complex protein 1 subunit beta (CCT2) OTW1VV4E TCPB_HUMAN Decreases Response To Substance [20]
Glutathione S-transferase 3, mitochondrial (MGST3) OTYK80JA MGST3_HUMAN Affects Response To Substance [27]
Filamin-A (FLNA) OTYZ9JXM FLNA_HUMAN Increases Response To Substance [20]
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⏷ Show the Full List of 57 DOT(s)

References

1 ClinicalTrials.gov (NCT00356824) Relationship Between HIV and Malaria in Ugandan Children
2 Drug information of Amodiaquine, 2008. eduDrugs.
3 Repurposing of clinically developed drugs for treatment of Middle East respiratory syndrome coronavirus infection. Antimicrob Agents Chemother. 2014 Aug;58(8):4885-93.
4 Artesunate FDA Label
5 The fight against drug-resistant malaria: novel plasmodial targets and antimalarial drugs. Curr Med Chem. 2008;15(2):161-71.
6 Effect of amodiaquine, a histamine N-methyltransferase inhibitor, on, Propionibacterium acnes and lipopolysaccharide-induced hepatitis in mice. Eur J Pharmacol. 2007 Mar 8;558(1-3):179-84.
7 Amodiaquine clearance and its metabolism to N-desethylamodiaquine is mediated by CYP2C8: a new high affinity and turnover enzyme-specific probe substrate. J Pharmacol Exp Ther. 2002 Feb;300(2):399-407.
8 Amodiaquine metabolism is impaired by common polymorphisms in CYP2C8: implications for malaria treatment in Africa. Clin Pharmacol Ther. 2007 Aug;82(2):197-203.
9 Human glutathione S-transferases- and NAD(P)H:quinone oxidoreductase 1-catalyzed inactivation of reactive quinoneimines of amodiaquine and N-desethylamodiaquine: possible implications for susceptibility to amodiaquine-induced liver toxicity. Toxicol Lett. 2017 Jun 5;275:83-91.
10 The bacterial P450 BM3: a prototype for a biocatalyst with human P450 activities. Trends Biotechnol. 2007 Jul;25(7):289-98.
11 Cytochrome P450 1A1/2 induction by antiparasitic drugs: dose-dependent increase in ethoxyresorufin O-deethylase activity and mRNA caused by quinine, primaquine and albendazole in HepG2 cells. Eur J Clin Pharmacol. 2002 Nov;58(8):537-42.
12 Apoptosis contributes to the cytotoxicity induced by amodiaquine and its major metabolite N-desethylamodiaquine in hepatic cells. Toxicol In Vitro. 2020 Feb;62:104669. doi: 10.1016/j.tiv.2019.104669. Epub 2019 Oct 16.
13 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.
14 An in vitro coculture system of human peripheral blood mononuclear cells with hepatocellular carcinoma-derived cells for predicting drug-induced liver injury. Arch Toxicol. 2021 Jan;95(1):149-168. doi: 10.1007/s00204-020-02882-4. Epub 2020 Aug 20.
15 High-throughput measurement of the Tp53 response to anticancer drugs and random compounds using a stably integrated Tp53-responsive luciferase reporter. Carcinogenesis. 2002 Jun;23(6):949-57. doi: 10.1093/carcin/23.6.949.
16 The antimalarial amodiaquine causes autophagic-lysosomal and proliferative blockade sensitizing human melanoma cells to starvation- and chemotherapy-induced cell death. Autophagy. 2013 Dec;9(12):2087-102. doi: 10.4161/auto.26506. Epub 2013 Oct 8.
17 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.
18 Combination treatment of malignant B cells using the anti-CD20 antibody rituximab and the anti-malarial artesunate. Int J Oncol. 2009 Jul;35(1):149-58.
19 Artesunate induces autophagy dependent apoptosis through upregulating ROS and activating AMPK-mTOR-ULK1 axis in human bladder cancer cells. Chem Biol Interact. 2020 Nov 1;331:109273. doi: 10.1016/j.cbi.2020.109273. Epub 2020 Sep 28.
20 Factors determining sensitivity or resistance of tumor cell lines towards artesunate. Chem Biol Interact. 2010 Apr 15;185(1):42-52.
21 Identification of human cytochrome P(450)s that metabolise anti-parasitic drugs and predictions of in vivo drug hepatic clearance from in vitro data. Eur J Clin Pharmacol. 2003 Sep;59(5-6):429-42.
22 Induction of APOBEC3C Facilitates the Genotoxic Stress-Mediated Cytotoxicity of Artesunate. Chem Res Toxicol. 2019 Dec 16;32(12):2526-2537. doi: 10.1021/acs.chemrestox.9b00358. Epub 2019 Nov 11.
23 Artesunate alleviates liver fibrosis by regulating ferroptosis signaling pathway. Biomed Pharmacother. 2019 Jan;109:2043-2053. doi: 10.1016/j.biopha.2018.11.030. Epub 2018 Nov 26.
24 Artesunate induces apoptosis through caspase-dependent and -independent mitochondrial pathways in human myelodysplastic syndrome SKM-1 cells. Chem Biol Interact. 2014 Aug 5;219:28-36. doi: 10.1016/j.cbi.2014.03.011. Epub 2014 Apr 3.
25 AMG900 as novel inhibitor of the translationally controlled tumor protein. Chem Biol Interact. 2021 Jan 25;334:109349. doi: 10.1016/j.cbi.2020.109349. Epub 2020 Nov 28.
26 Untargeted Proteomics and Systems-Based Mechanistic Investigation of Artesunate in Human Bronchial Epithelial Cells. Chem Res Toxicol. 2015 Oct 19;28(10):1903-13. doi: 10.1021/acs.chemrestox.5b00105. Epub 2015 Sep 21.
27 Glutathione-related enzymes contribute to resistance of tumor cells and low toxicity in normal organs to artesunate. In Vivo. 2005 Jan-Feb;19(1):225-32.
28 Mechanistic perspectives for 1,2,4-trioxanes in anti-cancer therapy. Drug Resist Updat. 2005 Feb-Apr;8(1-2):85-97. doi: 10.1016/j.drup.2005.04.003.