Details of the Drug Combination

General Information of Drug Combination (ID: DCNDOA2)

• Drug Combination Name: Artesunate + Chloroquine
• Indication: Uncomplicated Falciparum Malaria; Status: Phase 1 [1]
• Component Drugs:
  Artesunate (DMR27C8): Small molecular drug
  Chloroquine (DMSI5CB): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Artesunate

Disease Entry	ICD 11	Status	REF
Infection of P. falciparum	1F40	Approved	[2]
Malaria	1F40-1F45	Approved	[3]
Plasmodium falciparum malaria	1F40	Approved	[2]

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	[3]

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	[12]

Artesunate Interacts with 57 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Catalase (CAT)	OTHEBX9R	CATA_HUMAN	Increases Expression	[9]
Transcription factor Sp1 (SP1)	OTISPT4X	SP1_HUMAN	Decreases Expression	[9]
Glutathione S-transferase P (GSTP1)	OTLP0A0Y	GSTP1_HUMAN	Decreases Expression	[9]
Tumor necrosis factor receptor superfamily member 6 (FAS)	OTP9XG86	TNR6_HUMAN	Increases Expression	[9]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[9]
Serine/threonine-protein kinase Chk1 (CHEK1)	OTTTI622	CHK1_HUMAN	Increases Phosphorylation	[13]
Ubiquitin-like protein ATG12 (ATG12)	OTJRO09Y	ATG12_HUMAN	Increases Expression	[14]
Apoptosis-inducing factor 1, mitochondrial (AIFM1)	OTKPWB7Q	AIFM1_HUMAN	Affects Localization	[15]
Serine/threonine-protein kinase Chk2 (CHEK2)	OT8ZPCNS	CHK2_HUMAN	Increases Phosphorylation	[13]
Metalloproteinase inhibitor 1 (TIMP1)	OTOXC51H	TIMP1_HUMAN	Increases Expression	[14]
Fibronectin (FN1)	OTB5ZN4Q	FINC_HUMAN	Decreases Expression	[14]
Ferritin heavy chain (FTH1)	OT6IFS0O	FRIH_HUMAN	Decreases Expression	[14]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Expression	[16]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[15]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[15]
Matrix metalloproteinase-9 (MMP9)	OTB2QDAV	MMP9_HUMAN	Decreases Expression	[14]
Replication protein A 32 kDa subunit (RPA2)	OTZ54WAF	RFA2_HUMAN	Increases Phosphorylation	[13]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Phosphorylation	[13]
Desmin (DES)	OTI09KBW	DESM_HUMAN	Decreases Expression	[14]
Phospholipid hydroperoxide glutathione peroxidase GPX4 (GPX4)	OTRAFFX2	GPX4_HUMAN	Decreases Activity	[14]
Serine/threonine-protein kinase mTOR (MTOR)	OTHH8KU7	MTOR_HUMAN	Decreases Phosphorylation	[10]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Affects Expression	[15]
Actin, aortic smooth muscle (ACTA2)	OTEDLG8E	ACTA_HUMAN	Decreases Expression	[14]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[15]
Sequestosome-1 (SQSTM1)	OTGY5D5J	SQSTM_HUMAN	Decreases Expression	[14]
Nuclear receptor coactivator 4 (NCOA4)	OTRVU0UA	NCOA4_HUMAN	Decreases Expression	[14]
Nuclear factor erythroid 2-related factor 2 (NFE2L2)	OT0HENJ5	NF2L2_HUMAN	Affects Localization	[17]
Microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B)	OTUYHB84	MLP3B_HUMAN	Increases Lipidation	[10]
Autophagy protein 5 (ATG5)	OT4T5SMS	ATG5_HUMAN	Increases Expression	[14]
DNA dC->dU-editing enzyme APOBEC-3C (APOBEC3C)	OTPL0AI1	ABC3C_HUMAN	Increases Expression	[13]
Ubiquitin-like-conjugating enzyme ATG3 (ATG3)	OT28VBVK	ATG3_HUMAN	Increases Expression	[14]
Small ribosomal subunit protein uS8 (RPS15A)	OT0BUA12	RS15A_HUMAN	Decreases Response To Substance	[11]
Mitochondrial thiamine pyrophosphate carrier (SLC25A19)	OT157TY3	TPC_HUMAN	Decreases Response To Substance	[11]
Atypical kinase COQ8A, mitochondrial (COQ8A)	OT1ETSA2	COQ8A_HUMAN	Decreases Response To Substance	[11]
Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial (MTHFD2)	OT1LQSGX	MTDC_HUMAN	Decreases Response To Substance	[11]
Large ribosomal subunit protein uL30 (RPL7)	OT4WCQBE	RL7_HUMAN	Decreases Response To Substance	[11]
Glutamate--cysteine ligase regulatory subunit (GCLM)	OT6CP234	GSH0_HUMAN	Decreases Response To Substance	[18]
Integrin beta-1 (ITGB1)	OT6G1IAR	ITB1_HUMAN	Increases Response To Substance	[11]
CAP-Gly domain-containing linker protein 4 (CLIP4)	OT75KVQK	CLIP4_HUMAN	Increases Response To Substance	[11]
Glutathione S-transferase theta-2 (GSTT2)	OTANW3TJ	GST2_HUMAN	Affects Response To Substance	[18]
ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 2 (BST1)	OTAV5SE7	BST1_HUMAN	Increases Response To Substance	[11]
Small ribosomal subunit protein eS12 (RPS12)	OTBRQ8MS	RS12_HUMAN	Decreases Response To Substance	[11]
Dopamine beta-hydroxylase (DBH)	OTC6I2SP	DOPO_HUMAN	Increases Response To Substance	[11]
Glutamate--cysteine ligase catalytic subunit (GCLC)	OTESDI4D	GSH1_HUMAN	Decreases Response To Substance	[18]
Nck-associated protein 1 (NCKAP1)	OTEZQXXJ	NCKP1_HUMAN	Increases Response To Substance	[11]
Small ribosomal subunit protein eS32 (RPL41)	OTFW5IFO	RS32_HUMAN	Decreases Response To Substance	[11]
Translationally-controlled tumor protein (TPT1)	OTHMTRJU	TCTP_HUMAN	Affects Response To Substance	[19]
Nascent polypeptide-associated complex subunit alpha (NACA)	OTLP1KR3	NACA_HUMAN	Decreases Response To Substance	[11]
Glutathione S-transferase Mu 4 (GSTM4)	OTOTF8DU	GSTM4_HUMAN	Affects Response To Substance	[18]
Maleylacetoacetate isomerase (GSTZ1)	OTQ43JCE	MAAI_HUMAN	Affects Response To Substance	[18]
Large ribosomal subunit protein eL6 (RPL6)	OTRU71O4	RL6_HUMAN	Decreases Response To Substance	[11]
Small ribosomal subunit protein eS6 (RPS6)	OTT4D1LN	RS6_HUMAN	Decreases Response To Substance	[11]
Frizzled-7 (FZD7)	OTTK3F6E	FZD7_HUMAN	Increases Response To Substance	[11]
Serine/arginine-rich splicing factor 2 (SRSF2)	OTVDHO6U	SRSF2_HUMAN	Decreases Response To Substance	[11]
T-complex protein 1 subunit beta (CCT2)	OTW1VV4E	TCPB_HUMAN	Decreases Response To Substance	[11]
Glutathione S-transferase 3, mitochondrial (MGST3)	OTYK80JA	MGST3_HUMAN	Affects Response To Substance	[18]
Filamin-A (FLNA)	OTYZ9JXM	FLNA_HUMAN	Increases Response To Substance	[11]

Indication(s) of Chloroquine

Disease Entry	ICD 11	Status	REF
Malaria	1F40-1F45	Approved	[4]
Plasmodium falciparum malaria	1F40	Approved	[5]
Plasmodium malariae malaria	N.A.	Approved	[5]
Plasmodium ovale malaria	N.A.	Approved	[5]
Systemic lupus erythematosus	4A40.0	Approved	[5]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 3	[6]
Middle East Respiratory Syndrome (MERS)	1D64	Investigative	[7]
Severe acute respiratory syndrome (SARS)	1D65	Investigative	[8]

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	[20]
HUMAN glycosylation of host receptor (GHR)	TTZGK1R	N.A.	Inhibitor	[20]
Duffy antigen chemokine receptor (ACKR1)	TTKY2NS	ACKR1_HUMAN	Modulator	[21]

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	[22]
Multidrug and toxin extrusion protein 1 (SLC47A1)	DTZGT0P	S47A1_HUMAN	Substrate	[23]

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	[24]
Cytochrome P450 1A1 (CYP1A1)	DE6OQ3W	CP1A1_HUMAN	Metabolism	[25]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[26]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[24]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[27]

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	[28]
Cytochrome P450 2D6 (CYP2D6)	OTZJC802	CP2D6_HUMAN	Decreases Activity	[25]
Tumor necrosis factor receptor superfamily member 10A (TNFRSF10A)	OTBPCU2O	TR10A_HUMAN	Increases Expression	[29]
Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB)	OT9RDS3H	IKKB_HUMAN	Decreases Expression	[30]
Inhibitor of nuclear factor kappa-B kinase subunit alpha (CHUK)	OTLF4ZB1	IKKA_HUMAN	Decreases Expression	[30]
Trans-Golgi network integral membrane protein 2 (TGOLN2)	OTM647IV	TGON2_HUMAN	Affects Localization	[31]
Claudin-1 (CLDN1)	OT27KV99	CLD1_HUMAN	Increases Expression	[32]
Epidermal growth factor receptor (EGFR)	OTAPLO1S	EGFR_HUMAN	Decreases Expression	[33]
Metalloproteinase inhibitor 1 (TIMP1)	OTOXC51H	TIMP1_HUMAN	Decreases Expression	[14]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Decreases Expression	[34]
Interleukin-1 alpha (IL1A)	OTPSGILV	IL1A_HUMAN	Increases Expression	[35]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Decreases Expression	[36]
Ferritin heavy chain (FTH1)	OT6IFS0O	FRIH_HUMAN	Increases Expression	[14]
Receptor tyrosine-protein kinase erbB-2 (ERBB2)	OTOAUNCK	ERBB2_HUMAN	Decreases Expression	[33]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Activity	[37]
Sodium/potassium-transporting ATPase subunit alpha-1 (ATP1A1)	OTCJ458Q	AT1A1_HUMAN	Increases Expression	[38]
Apolipoprotein D (APOD)	OTT77XW8	APOD_HUMAN	Affects Localization	[39]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Decreases Expression	[34]
Cathepsin B (CTSB)	OTP9G5QB	CATB_HUMAN	Decreases Activity	[40]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Decreases Expression	[29]
72 kDa type IV collagenase (MMP2)	OT5NIWA2	MMP2_HUMAN	Decreases Expression	[41]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[42]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[35]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Increases Expression	[35]
Matrix metalloproteinase-9 (MMP9)	OTB2QDAV	MMP9_HUMAN	Decreases Expression	[41]
Glutamine synthetase (GLUL)	OTYGTCGF	GLNA_HUMAN	Decreases Expression	[43]
CCAAT/enhancer-binding protein beta (CEBPB)	OTM9MQIA	CEBPB_HUMAN	Increases Expression	[44]
Nuclear factor NF-kappa-B p105 subunit (NFKB1)	OTNRRD8I	NFKB1_HUMAN	Decreases Expression	[30]
Cation-dependent mannose-6-phosphate receptor (M6PR)	OTFEWOSB	MPRD_HUMAN	Affects Localization	[31]
Receptor tyrosine-protein kinase erbB-3 (ERBB3)	OTRSST0A	ERBB3_HUMAN	Decreases Expression	[33]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[45]
Calreticulin (CALR)	OTYD2TR1	CALR_HUMAN	Increases Expression	[44]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[45]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Decreases Phosphorylation	[46]
Multidrug resistance-associated protein 1 (ABCC1)	OTGUN89S	MRP1_HUMAN	Decreases Expression	[29]
DNA damage-inducible transcript 3 protein (DDIT3)	OTI8YKKE	DDIT3_HUMAN	Increases Expression	[44]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[47]
Aquaporin-2 (AQP2)	OTQLBKK6	AQP2_HUMAN	Decreases Expression	[48]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Cleavage	[49]
Collagenase 3 (MMP13)	OTY8BZIE	MMP13_HUMAN	Increases Expression	[41]
Coatomer subunit delta (ARCN1)	OTJ96STE	COPD_HUMAN	Affects Localization	[31]
Eotaxin (CCL11)	OT3BIFPK	CCL11_HUMAN	Decreases Secretion	[50]
Microsomal triglyceride transfer protein large subunit (MTTP)	OTNUVSDT	MTP_HUMAN	Increases Expression	[51]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Cleavage	[49]
Gamma-aminobutyric acid receptor-associated protein-like 2 (GABARAPL2)	OTS7YVHF	GBRL2_HUMAN	Increases Expression	[43]
Interleukin-2 (IL2)	OTGI4NSA	IL2_HUMAN	Decreases Expression	[52]
Rho-related GTP-binding protein RhoB (RHOB)	OTHQFQF7	RHOB_HUMAN	Increases Expression	[43]
Transcription factor p65 (RELA)	OTUJP9CN	TF65_HUMAN	Decreases Expression	[30]
Recombining binding protein suppressor of hairless (RBPJ)	OTD7CUG0	SUH_HUMAN	Increases Expression	[53]
Lymphotoxin-beta (LTB)	OTUFS8CF	TNFC_HUMAN	Increases Expression	[35]
Golgin subfamily A member 2 (GOLGA2)	OT5S9KYM	GOGA2_HUMAN	Affects Localization	[31]
BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3)	OT4SO7J4	BNIP3_HUMAN	Increases Expression	[54]
Serine-protein kinase ATM (ATM)	OTQVOHLT	ATM_HUMAN	Increases Phosphorylation	[55]
Sequestosome-1 (SQSTM1)	OTGY5D5J	SQSTM_HUMAN	Increases Expression	[56]
Solute carrier family 12 member 1 (SLC12A1)	OT6YSX0G	S12A1_HUMAN	Decreases Expression	[48]
Nuclear receptor coactivator 4 (NCOA4)	OTRVU0UA	NCOA4_HUMAN	Increases Expression	[14]
Beclin-1 (BECN1)	OT4X293M	BECN1_HUMAN	Decreases Expression	[57]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Increases Cleavage	[29]
Early endosome antigen 1 (EEA1)	OTIBXC1B	EEA1_HUMAN	Affects Localization	[31]
Occludin (OCLN)	OTSUTVWL	OCLN_HUMAN	Increases Expression	[32]
Hypoxia-inducible factor 1-alpha (HIF1A)	OTADSC03	HIF1A_HUMAN	Decreases Expression	[45]
ATP-binding cassette sub-family C member 2 (ABCC2)	OTJSIGV5	MRP2_HUMAN	Decreases Expression	[29]
Tribbles homolog 3 (TRIB3)	OTG5OS7X	TRIB3_HUMAN	Increases Expression	[44]
Microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B)	OTUYHB84	MLP3B_HUMAN	Increases Expression	[58]
Autophagy protein 5 (ATG5)	OT4T5SMS	ATG5_HUMAN	Increases Expression	[40]
Microtubule-associated proteins 1A/1B light chain 3A (MAP1LC3A)	OTPMGIU4	MLP3A_HUMAN	Increases Expression	[59]
Toll-like receptor 9 (TLR9)	OTFZ45HX	TLR9_HUMAN	Increases Expression	[41]
Toll-like receptor 8 (TLR8)	OTEJRL9C	TLR8_HUMAN	Decreases Activity	[60]
NAD-dependent protein deacetylase sirtuin-3, mitochondrial (SIRT3)	OTMEF544	SIR3_HUMAN	Increases Stability	[61]
Toll-like receptor 7 (TLR7)	OT3HZV7Z	TLR7_HUMAN	Decreases Activity	[60]
Programmed cell death 1 ligand 1 (CD274)	OTJ0VFDL	PD1L1_HUMAN	Decreases Expression	[29]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2)	OTW8V2V1	ABCG2_HUMAN	Decreases Expression	[29]
NF-kappa-B essential modulator (IKBKG)	OTNWJWSD	NEMO_HUMAN	Decreases Expression	[30]
Solute carrier organic anion transporter family member 1B1 (SLCO1B1)	OTNEN8QK	SO1B1_HUMAN	Affects Localization	[38]
Porphobilinogen deaminase (HMBS)	OT3P47DC	HEM3_HUMAN	Increases Response To Substance	[62]
Cytochrome P450 2C8 (CYP2C8)	OTHCWT42	CP2C8_HUMAN	Increases Metabolism	[63]
Linker for activation of T-cells family member 2 (LAT2)	OTWJDKIH	NTAL_HUMAN	Increases Response To Substance	[64]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Plasmodium Falciparum Infection	DCPMMUQ	N. A.	Phase 1	[65]

References

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