Details of the Drug Combination

General Information of Drug Combination (ID: DC5QFXT)

• Drug Combination Name: Chloroquine + Hydroxychloroquine
• Indication: COVID; Status: Phase 3 [1]
• Component Drugs:
  Chloroquine (DMSI5CB): Small molecular drug
  Hydroxychloroquine (DMSIVND): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Chloroquine

Disease Entry	ICD 11	Status	REF
Malaria	1F40-1F45	Approved	[2]
Plasmodium falciparum malaria	1F40	Approved	[3]
Plasmodium malariae malaria	N.A.	Approved	[3]
Plasmodium ovale malaria	N.A.	Approved	[3]
Systemic lupus erythematosus	4A40.0	Approved	[3]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 3	[4]
Middle East Respiratory Syndrome (MERS)	1D64	Investigative	[5]
Severe acute respiratory syndrome (SARS)	1D65	Investigative	[6]

Chloroquine Interacts with 3 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	[10]
HUMAN glycosylation of host receptor (GHR)	TTZGK1R	N.A.	Inhibitor	[10]
Duffy antigen chemokine receptor (ACKR1)	TTKY2NS	ACKR1_HUMAN	Modulator	[11]

Chloroquine Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[12]
Multidrug and toxin extrusion protein 1 (SLC47A1)	DTZGT0P	S47A1_HUMAN	Substrate	[13]

Chloroquine Interacts with 5 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[14]
Cytochrome P450 1A1 (CYP1A1)	DE6OQ3W	CP1A1_HUMAN	Metabolism	[15]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[16]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[14]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[17]

Chloroquine Interacts with 77 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Decreases Activity	[18]
Cytochrome P450 2D6 (CYP2D6)	OTZJC802	CP2D6_HUMAN	Decreases Activity	[15]
Tumor necrosis factor receptor superfamily member 10A (TNFRSF10A)	OTBPCU2O	TR10A_HUMAN	Increases Expression	[19]
Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB)	OT9RDS3H	IKKB_HUMAN	Decreases Expression	[20]
Inhibitor of nuclear factor kappa-B kinase subunit alpha (CHUK)	OTLF4ZB1	IKKA_HUMAN	Decreases Expression	[20]
Trans-Golgi network integral membrane protein 2 (TGOLN2)	OTM647IV	TGON2_HUMAN	Affects Localization	[21]
Claudin-1 (CLDN1)	OT27KV99	CLD1_HUMAN	Increases Expression	[22]
Epidermal growth factor receptor (EGFR)	OTAPLO1S	EGFR_HUMAN	Decreases Expression	[23]
Metalloproteinase inhibitor 1 (TIMP1)	OTOXC51H	TIMP1_HUMAN	Decreases Expression	[24]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Decreases Expression	[25]
Interleukin-1 alpha (IL1A)	OTPSGILV	IL1A_HUMAN	Increases Expression	[26]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Decreases Expression	[27]
Ferritin heavy chain (FTH1)	OT6IFS0O	FRIH_HUMAN	Increases Expression	[24]
Receptor tyrosine-protein kinase erbB-2 (ERBB2)	OTOAUNCK	ERBB2_HUMAN	Decreases Expression	[23]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Activity	[28]
Sodium/potassium-transporting ATPase subunit alpha-1 (ATP1A1)	OTCJ458Q	AT1A1_HUMAN	Increases Expression	[29]
Apolipoprotein D (APOD)	OTT77XW8	APOD_HUMAN	Affects Localization	[30]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Decreases Expression	[25]
Cathepsin B (CTSB)	OTP9G5QB	CATB_HUMAN	Decreases Activity	[31]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Decreases Expression	[19]
72 kDa type IV collagenase (MMP2)	OT5NIWA2	MMP2_HUMAN	Decreases Expression	[32]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[33]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[26]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Increases Expression	[26]
Matrix metalloproteinase-9 (MMP9)	OTB2QDAV	MMP9_HUMAN	Decreases Expression	[32]
Glutamine synthetase (GLUL)	OTYGTCGF	GLNA_HUMAN	Decreases Expression	[34]
CCAAT/enhancer-binding protein beta (CEBPB)	OTM9MQIA	CEBPB_HUMAN	Increases Expression	[35]
Nuclear factor NF-kappa-B p105 subunit (NFKB1)	OTNRRD8I	NFKB1_HUMAN	Decreases Expression	[20]
Cation-dependent mannose-6-phosphate receptor (M6PR)	OTFEWOSB	MPRD_HUMAN	Affects Localization	[21]
Receptor tyrosine-protein kinase erbB-3 (ERBB3)	OTRSST0A	ERBB3_HUMAN	Decreases Expression	[23]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[36]
Calreticulin (CALR)	OTYD2TR1	CALR_HUMAN	Increases Expression	[35]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[36]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Decreases Phosphorylation	[37]
Multidrug resistance-associated protein 1 (ABCC1)	OTGUN89S	MRP1_HUMAN	Decreases Expression	[19]
DNA damage-inducible transcript 3 protein (DDIT3)	OTI8YKKE	DDIT3_HUMAN	Increases Expression	[35]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[38]
Aquaporin-2 (AQP2)	OTQLBKK6	AQP2_HUMAN	Decreases Expression	[39]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Cleavage	[40]
Collagenase 3 (MMP13)	OTY8BZIE	MMP13_HUMAN	Increases Expression	[32]
Coatomer subunit delta (ARCN1)	OTJ96STE	COPD_HUMAN	Affects Localization	[21]
Eotaxin (CCL11)	OT3BIFPK	CCL11_HUMAN	Decreases Secretion	[41]
Microsomal triglyceride transfer protein large subunit (MTTP)	OTNUVSDT	MTP_HUMAN	Increases Expression	[42]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Cleavage	[40]
Gamma-aminobutyric acid receptor-associated protein-like 2 (GABARAPL2)	OTS7YVHF	GBRL2_HUMAN	Increases Expression	[34]
Interleukin-2 (IL2)	OTGI4NSA	IL2_HUMAN	Decreases Expression	[43]
Rho-related GTP-binding protein RhoB (RHOB)	OTHQFQF7	RHOB_HUMAN	Increases Expression	[34]
Transcription factor p65 (RELA)	OTUJP9CN	TF65_HUMAN	Decreases Expression	[20]
Recombining binding protein suppressor of hairless (RBPJ)	OTD7CUG0	SUH_HUMAN	Increases Expression	[44]
Lymphotoxin-beta (LTB)	OTUFS8CF	TNFC_HUMAN	Increases Expression	[26]
Golgin subfamily A member 2 (GOLGA2)	OT5S9KYM	GOGA2_HUMAN	Affects Localization	[21]
BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3)	OT4SO7J4	BNIP3_HUMAN	Increases Expression	[45]
Serine-protein kinase ATM (ATM)	OTQVOHLT	ATM_HUMAN	Increases Phosphorylation	[46]
Sequestosome-1 (SQSTM1)	OTGY5D5J	SQSTM_HUMAN	Increases Expression	[47]
Solute carrier family 12 member 1 (SLC12A1)	OT6YSX0G	S12A1_HUMAN	Decreases Expression	[39]
Nuclear receptor coactivator 4 (NCOA4)	OTRVU0UA	NCOA4_HUMAN	Increases Expression	[24]
Beclin-1 (BECN1)	OT4X293M	BECN1_HUMAN	Decreases Expression	[48]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Increases Cleavage	[19]
Early endosome antigen 1 (EEA1)	OTIBXC1B	EEA1_HUMAN	Affects Localization	[21]
Occludin (OCLN)	OTSUTVWL	OCLN_HUMAN	Increases Expression	[22]
Hypoxia-inducible factor 1-alpha (HIF1A)	OTADSC03	HIF1A_HUMAN	Decreases Expression	[36]
ATP-binding cassette sub-family C member 2 (ABCC2)	OTJSIGV5	MRP2_HUMAN	Decreases Expression	[19]
Tribbles homolog 3 (TRIB3)	OTG5OS7X	TRIB3_HUMAN	Increases Expression	[35]
Microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B)	OTUYHB84	MLP3B_HUMAN	Increases Expression	[49]
Autophagy protein 5 (ATG5)	OT4T5SMS	ATG5_HUMAN	Increases Expression	[31]
Microtubule-associated proteins 1A/1B light chain 3A (MAP1LC3A)	OTPMGIU4	MLP3A_HUMAN	Increases Expression	[50]
Toll-like receptor 9 (TLR9)	OTFZ45HX	TLR9_HUMAN	Increases Expression	[32]
Toll-like receptor 8 (TLR8)	OTEJRL9C	TLR8_HUMAN	Decreases Activity	[51]
NAD-dependent protein deacetylase sirtuin-3, mitochondrial (SIRT3)	OTMEF544	SIR3_HUMAN	Increases Stability	[52]
Toll-like receptor 7 (TLR7)	OT3HZV7Z	TLR7_HUMAN	Decreases Activity	[51]
Programmed cell death 1 ligand 1 (CD274)	OTJ0VFDL	PD1L1_HUMAN	Decreases Expression	[19]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2)	OTW8V2V1	ABCG2_HUMAN	Decreases Expression	[19]
NF-kappa-B essential modulator (IKBKG)	OTNWJWSD	NEMO_HUMAN	Decreases Expression	[20]
Solute carrier organic anion transporter family member 1B1 (SLCO1B1)	OTNEN8QK	SO1B1_HUMAN	Affects Localization	[29]
Porphobilinogen deaminase (HMBS)	OT3P47DC	HEM3_HUMAN	Increases Response To Substance	[53]
Cytochrome P450 2C8 (CYP2C8)	OTHCWT42	CP2C8_HUMAN	Increases Metabolism	[54]
Linker for activation of T-cells family member 2 (LAT2)	OTWJDKIH	NTAL_HUMAN	Increases Response To Substance	[55]

Indication(s) of Hydroxychloroquine

Disease Entry	ICD 11	Status	REF
Chronic renal failure	GB61.Z	Approved	[7]
Malaria	1F40-1F45	Approved	[8]
Plasmodium falciparum malaria	1F40	Approved	[7]
Plasmodium malariae malaria	N.A.	Approved	[7]
Plasmodium ovale malaria	N.A.	Approved	[7]
Systemic lupus erythematosus	4A40.0	Approved	[7]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 3	[9]
Colon cancer	2B90.Z	Investigative	[7]

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	[10]
HUMAN glycosylation of host receptor (GHR)	TTZGK1R	N.A.	Inhibitor	[10]
Toll-like receptor 7 (TLR7)	TTRJ1K4	TLR7_HUMAN	Antagonist	[56]
HUMAN toll-like receptor 7/9 signalling pathway (TLR7/9 pathway)	TT3A1EZ	N.A.	Inhibitor	[57]

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	[58]

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	[59]

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	[60]
Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3)	OTPGHZB9	IFIT3_HUMAN	Increases Expression	[61]
CASP8 and FADD-like apoptosis regulator (CFLAR)	OTX14BAS	CFLAR_HUMAN	Decreases Expression	[62]
Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1)	OTY9R6FZ	ERN1_HUMAN	Increases Expression	[61]
Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1)	OT4TMERS	NFAC1_HUMAN	Affects Expression	[63]
Claudin-1 (CLDN1)	OT27KV99	CLD1_HUMAN	Increases Expression	[22]
Interferon beta (IFNB1)	OTYQGUB5	IFNB_HUMAN	Increases Expression	[61]
C-X-C motif chemokine 10 (CXCL10)	OTTLQ6S0	CXL10_HUMAN	Increases Expression	[61]
3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR)	OTRT3F3U	HMDH_HUMAN	Affects Expression	[64]
Alkaline phosphatase, tissue-nonspecific isozyme (ALPL)	OTG7J4BP	PPBT_HUMAN	Affects Expression	[64]
Transcription factor Jun (JUN)	OTCYBO6X	JUN_HUMAN	Increases Phosphorylation	[61]
Cathepsin B (CTSB)	OTP9G5QB	CATB_HUMAN	Affects Localization	[65]
72 kDa type IV collagenase (MMP2)	OT5NIWA2	MMP2_HUMAN	Decreases Expression	[66]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[26]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Increases Expression	[26]
NF-kappa-B inhibitor alpha (NFKBIA)	OTFT924M	IKBA_HUMAN	Increases Degradation	[61]
CD40 ligand (CD40LG)	OT75Z6A6	CD40L_HUMAN	Decreases Expression	[63]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[62]
Transcription factor p65 (RELA)	OTUJP9CN	TF65_HUMAN	Increases Expression	[61]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Activity	[65]
TNF receptor-associated factor 3 (TRAF3)	OT5TQBGV	TRAF3_HUMAN	Increases Expression	[61]
Nuclear factor of activated T-cells, cytoplasmic 2 (NFATC2)	OTK5T6HZ	NFAC2_HUMAN	Affects Localization	[63]
Sequestosome-1 (SQSTM1)	OTGY5D5J	SQSTM_HUMAN	Increases Expression	[67]
Interferon regulatory factor 3 (IRF3)	OT81U8ME	IRF3_HUMAN	Increases Phosphorylation	[61]
Occludin (OCLN)	OTSUTVWL	OCLN_HUMAN	Increases Expression	[22]
Mitochondrial antiviral-signaling protein (MAVS)	OTTQ0J64	MAVS_HUMAN	Increases Expression	[61]
S-adenosylmethionine-dependent nucleotide dehydratase RSAD2 (RSAD2)	OTCA9WCM	RSAD2_HUMAN	Increases Expression	[61]
Interferon-induced helicase C domain-containing protein 1 (IFIH1)	OTZA2AHA	IFIH1_HUMAN	Increases Expression	[61]
Toll-like receptor 9 (TLR9)	OTFZ45HX	TLR9_HUMAN	Decreases Expression	[68]
7-dehydrocholesterol reductase (DHCR7)	OTLILBUI	DHCR7_HUMAN	Affects Expression	[64]

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