Details of the Drug Combination

General Information of Drug Combination (ID: DC0UV24)

• Drug Combination Name: Teriflunomide + Tetracycline
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Teriflunomide (DMQ2FKJ): Small molecular drug
  Tetracycline (DMZA017): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 10.06
  Bliss Independence Score: 10.06
  Loewe Additivity Score: 23.7
  LHighest Single Agent (HSA) Score: 23.72

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Teriflunomide

Disease Entry	ICD 11	Status	REF
Hyperlipidaemia	5C80	Approved	[2]
Lupus nephritis	4A40.0Y	Approved	[3]
Multiple sclerosis	8A40	Approved	[4]
Psoriatic arthritis	FA21	Approved	[3]
Rheumatoid arthritis	FA20	Phase 3	[4]
Hepatitis B virus infection	1E51.0	Phase 1	[2]

Teriflunomide Interacts with 3 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Plasmodium Dihydroorotate dehydrogenase (Malaria DHOdehase)	TT3PQ2Y	PYRD_PLAF7	Inhibitor	[7]
HMG-CoA reductase (HMGCR)	TTPADOQ	HMDH_HUMAN	Inhibitor	[2]
Dihydroorotate dehydrogenase (DHODH)	TTLVP78	PYRD_HUMAN	Modulator	[8]

Teriflunomide 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]

Teriflunomide Interacts with 33 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Phenylalanine--tRNA ligase, mitochondrial (FARS2)	OTXAK6F0	SYFM_HUMAN	Decreases Expression	[10]
Ornithine aminotransferase, mitochondrial (OAT)	OTEKO8CT	OAT_HUMAN	Increases Expression	[10]
Heat shock 70 kDa protein 1-like (HSPA1L)	OTC2V1K6	HS71L_HUMAN	Decreases Expression	[10]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Expression	[10]
1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial (CYP24A1)	OTG2T749	CP24A_HUMAN	Decreases Expression	[10]
BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3)	OT4SO7J4	BNIP3_HUMAN	Increases Expression	[10]
Mitochondrial adenyl nucleotide antiporter SLC25A25 (SLC25A25)	OTMNPSNY	SCMC2_HUMAN	Increases Expression	[10]
Mitochondrial fission regulator 2 (MTFR2)	OTLOR68D	MTFR2_HUMAN	Decreases Expression	[10]
Choline dehydrogenase, mitochondrial (CHDH)	OTO2DPGL	CHDH_HUMAN	Decreases Expression	[10]
Dimethyladenosine transferase 1, mitochondrial (TFB1M)	OTFCUSAZ	TFB1M_HUMAN	Decreases Expression	[10]
Probable ATP-dependent RNA helicase DDX28 (DDX28)	OTIIHNYN	DDX28_HUMAN	Decreases Expression	[10]
Glucocorticoid receptor (NR3C1)	OTCI2YDI	GCR_HUMAN	Increases Activity	[11]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Expression	[11]
Cytochrome P450 2C9 (CYP2C9)	OTGLBN29	CP2C9_HUMAN	Increases Expression	[11]
Cytochrome P450 2B6 (CYP2B6)	OTOYO4S7	CP2B6_HUMAN	Increases Expression	[11]
Phosphoenolpyruvate carboxykinase, cytosolic (PCK1)	OTNWEJ5Y	PCKGC_HUMAN	Increases Expression	[11]
Glucose-6-phosphatase catalytic subunit 1 (G6PC1)	OTJ6FM9F	G6PC1_HUMAN	Increases Expression	[11]
Fatty acid synthase (FASN)	OTFII9KG	FAS_HUMAN	Decreases Expression	[11]
Nuclear receptor subfamily 1 group I member 3 (NR1I3)	OTS3SGH7	NR1I3_HUMAN	Increases Expression	[11]
Glycophorin-A (GYPA)	OTABU4YV	GLPA_HUMAN	Increases Expression	[12]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Expression	[13]
Retinoblastoma-associated protein (RB1)	OTQJUJMZ	RB_HUMAN	Decreases Expression	[14]
Cyclin-A2 (CCNA2)	OTPHHYZJ	CCNA2_HUMAN	Increases Expression	[12]
Ribosomal protein S6 kinase beta-1 (RPS6KB1)	OTAELNGX	KS6B1_HUMAN	Decreases Phosphorylation	[14]
G1/S-specific cyclin-E1 (CCNE1)	OTLD7UID	CCNE1_HUMAN	Decreases Expression	[14]
C-X-C chemokine receptor type 1 (CXCR1)	OT5512B2	CXCR1_HUMAN	Decreases Expression	[13]
G1/S-specific cyclin-D2 (CCND2)	OTDULQF9	CCND2_HUMAN	Decreases Expression	[14]
M-phase inducer phosphatase 1 (CDC25A)	OTSLKKCO	MPIP1_HUMAN	Decreases Expression	[14]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Decreases Phosphorylation	[14]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[12]
Heat shock factor protein 1 (HSF1)	OTYNJ4KP	HSF1_HUMAN	Increases Activity	[15]
Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1)	OTHBQVD5	4EBP1_HUMAN	Decreases Phosphorylation	[14]
Interleukin-10 receptor subunit alpha (IL10RA)	OTOX3D1D	I10R1_HUMAN	Increases Expression	[13]

Indication(s) of Tetracycline

Disease Entry	ICD 11	Status	REF
Acne vulgaris	ED80	Approved	[5]
Actinomycosis	N.A.	Approved	[5]
Acute gonococcal cervicitis	N.A.	Approved	[5]
Acute gonococcal epididymo-orchitis	N.A.	Approved	[5]
Bacterial infection	1A00-1C4Z	Approved	[6]
Bronchitis	CA20	Approved	[5]
Brucellosis	N.A.	Approved	[5]
Lymphogranuloma venereum	N.A.	Approved	[5]
Ornithosis	N.A.	Approved	[5]
Pneumonia	CA40	Approved	[5]
Q fever	N.A.	Approved	[5]
Relapsing fever	N.A.	Approved	[5]
Rickettsialpox	N.A.	Approved	[5]
Rocky mountain spotted fever	N.A.	Approved	[5]
Syphilis	N.A.	Approved	[5]
Trachoma	N.A.	Approved	[5]
Typhus	N.A.	Approved	[5]
Urinary tract infection	GC08	Approved	[5]
Yaws	N.A.	Approved	[5]
Pelvic inflammatory disease	GA05	Investigative	[5]
Sinusitis	CA0A.Z	Investigative	[5]

Tetracycline Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Staphylococcus 30S ribosomal subunit (Stap-coc pbp2)	TTQ8KVI	F4NA87_STAAU	Binder	[17]

Tetracycline Interacts with 5 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[18]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[19]
Organic anion transporter 2 (SLC22A7)	DT0OC1Q	S22A7_HUMAN	Substrate	[20]
Organic anion transporter 3 (SLC22A8)	DTVP67E	S22A8_HUMAN	Substrate	[20]
Organic anion transporter 4 (SLC22A11)	DT06JWZ	S22AB_HUMAN	Substrate	[20]

Tetracycline Interacts with 44 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Solute carrier family 22 member 7 (SLC22A7)	OTKTNH1W	S22A7_HUMAN	Increases Transport	[21]
Organic anion transporter 3 (SLC22A8)	OT8BY933	S22A8_HUMAN	Increases Uptake	[20]
Glutathione S-transferase P (GSTP1)	OTLP0A0Y	GSTP1_HUMAN	Decreases Activity	[22]
Glutathione S-transferase Mu 3 (GSTM3)	OTLA2WJT	GSTM3_HUMAN	Decreases Activity	[22]
Nuclear protein 1 (NUPR1)	OT4FU8C0	NUPR1_HUMAN	Increases Expression	[16]
Alpha-1-antichymotrypsin (SERPINA3)	OT9BP2S0	AACT_HUMAN	Increases Expression	[16]
Asparagine synthetase (ASNS)	OT8R922G	ASNS_HUMAN	Increases Expression	[16]
Inhibin beta E chain (INHBE)	OTOI2NYG	INHBE_HUMAN	Increases Expression	[16]
AP-1 complex subunit sigma-1A (AP1S1)	OTQ2H8DN	AP1S1_HUMAN	Decreases Expression	[16]
Transgelin (TAGLN)	OTAEZ0KP	TAGL_HUMAN	Decreases Expression	[16]
Fibronectin type III domain-containing protein 4 (FNDC4)	OTOQK0WK	FNDC4_HUMAN	Increases Expression	[16]
Protein DEPP1 (DEPP1)	OTB36PHJ	DEPP1_HUMAN	Increases Expression	[16]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Expression	[23]
Alternative prion protein (PRNP)	OTE85L1Q	APRIO_HUMAN	Affects Binding	[24]
Claudin-11 (CLDN11)	OTNN6UTL	CLD11_HUMAN	Decreases Expression	[25]
72 kDa type IV collagenase (MMP2)	OT5NIWA2	MMP2_HUMAN	Decreases Activity	[26]
Stromelysin-1 (MMP3)	OTGBI74Z	MMP3_HUMAN	Decreases Activity	[26]
Integrin alpha-5 (ITGA5)	OT3RCI67	ITA5_HUMAN	Increases Expression	[25]
Insulin-like growth factor-binding protein 1 (IGFBP1)	OT6UQV2K	IBP1_HUMAN	Increases Expression	[27]
Integrin alpha-M (ITGAM)	OTAG6HWU	ITAM_HUMAN	Decreases Expression	[25]
DNA topoisomerase 2-alpha (TOP2A)	OT6LPS08	TOP2A_HUMAN	Decreases Expression	[28]
Integrin alpha-L (ITGAL)	OTCUQAIS	ITAL_HUMAN	Decreases Expression	[25]
Neutrophil collagenase (MMP8)	OTZXH19L	MMP8_HUMAN	Decreases Activity	[26]
Integrin alpha-3 (ITGA3)	OTBCH21D	ITA3_HUMAN	Decreases Expression	[25]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[29]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[29]
Sterol regulatory element-binding protein 1 (SREBF1)	OTWBRPAI	SRBP1_HUMAN	Increases Expression	[27]
Collagenase 3 (MMP13)	OTY8BZIE	MMP13_HUMAN	Decreases Activity	[26]
Gap junction alpha-8 protein (GJA8)	OTZCPRKD	CXA8_HUMAN	Decreases Expression	[25]
Microsomal triglyceride transfer protein large subunit (MTTP)	OTNUVSDT	MTP_HUMAN	Decreases Expression	[27]
Claudin-15 (CLDN15)	OT9K0KI7	CLD15_HUMAN	Decreases Expression	[25]
Claudin-6 (CLDN6)	OTEN8ID2	CLD6_HUMAN	Decreases Expression	[25]
Claudin-8 (CLDN8)	OT7IIWXG	CLD8_HUMAN	Decreases Expression	[25]
Claudin-2 (CLDN2)	OTRF3D6Y	CLD2_HUMAN	Decreases Expression	[25]
Claudin-10 (CLDN10)	OT2CVAKY	CLD10_HUMAN	Decreases Expression	[25]
Peroxisomal bifunctional enzyme (EHHADH)	OTBAAHL5	ECHP_HUMAN	Decreases Expression	[27]
Diacylglycerol O-acyltransferase 2 (DGAT2)	OTE5PDD0	DGAT2_HUMAN	Increases Expression	[29]
Neurogenic locus notch homolog protein 4 (NOTCH4)	OTBCHB61	NOTC4_HUMAN	Decreases Expression	[25]
Angiotensin-converting enzyme 2 (ACE2)	OTTRZGU7	ACE2_HUMAN	Increases Expression	[30]
Gap junction delta-2 protein (GJD2)	OTDR288R	CXD2_HUMAN	Decreases Expression	[25]
Neurogenic locus notch homolog protein 3 (NOTCH3)	OTMVVA7F	NOTC3_HUMAN	Decreases Expression	[25]
Solute carrier family 22 member 6 (SLC22A6)	OTKRCBVM	S22A6_HUMAN	Increases Export	[20]
ATP-binding cassette sub-family C member 4 (ABCC4)	OTO27PAL	MRP4_HUMAN	Increases Transport	[31]
Organic anion transporter 7 (SLC22A9)	OTO4BJCC	S22A9_HUMAN	Increases Export	[20]

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