Details of the Drug Combination

General Information of Drug Combination (ID: DC4F5LE)

• Drug Combination Name: Cilostazol + Tetracycline
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Cilostazol (DMZMSCT): Small molecular drug
  Tetracycline (DMZA017): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 6.94
  Bliss Independence Score: 6.94
  Loewe Additivity Score: 20.8
  LHighest Single Agent (HSA) Score: 20.82

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Cilostazol

Disease Entry	ICD 11	Status	REF
Intermittent claudication	BD40.00	Approved	[2]

Cilostazol Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Phosphodiesterase 3 (PDE3)	TTZCG4L	NOUNIPROTAC	Modulator	[5]
Phosphodiesterase 3A (PDE3A)	TT06AWU	PDE3A_HUMAN	Inhibitor	[6]

Cilostazol Interacts with 3 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[7]
Organic anion transporter 3 (SLC22A8)	DTVP67E	S22A8_HUMAN	Substrate	[8]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[7]

Cilostazol Interacts with 6 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[9]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[9]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[9]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[9]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[9]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[9]

Cilostazol Interacts with 20 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Apoptosis-inducing factor 1, mitochondrial (AIFM1)	OTKPWB7Q	AIFM1_HUMAN	Increases Localization	[10]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Decreases Response To Substance	[11]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Expression	[12]
Heme oxygenase 1 (HMOX1)	OTC1W6UX	HMOX1_HUMAN	Increases Expression	[10]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[10]
Proliferating cell nuclear antigen (PCNA)	OTHZ1RIA	PCNA_HUMAN	Decreases Expression	[13]
Cystic fibrosis transmembrane conductance regulator (CFTR)	OT6B22QH	CFTR_HUMAN	Increases Activity	[14]
Cyclin-A2 (CCNA2)	OTPHHYZJ	CCNA2_HUMAN	Decreases Expression	[13]
NF-kappa-B inhibitor alpha (NFKBIA)	OTFT924M	IKBA_HUMAN	Increases Expression	[10]
Nitric oxide synthase 3 (NOS3)	OTLDT7NR	NOS3_HUMAN	Increases Phosphorylation	[15]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Increases Phosphorylation	[15]
Peroxisome proliferator-activated receptor gamma (PPARG)	OTHMARHO	PPARG_HUMAN	Increases Activity	[11]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[12]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[10]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Activity	[16]
Transcription factor E2F1 (E2F1)	OTLKYBBC	E2F1_HUMAN	Decreases Expression	[13]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[16]
Transcription factor E2F2 (E2F2)	OTO75RM7	E2F2_HUMAN	Decreases Expression	[13]
Nuclear factor erythroid 2-related factor 2 (NFE2L2)	OT0HENJ5	NF2L2_HUMAN	Increases Expression	[10]
NAD-dependent protein deacetylase sirtuin-1 (SIRT1)	OTAYZMOY	SIR1_HUMAN	Increases Expression	[15]

Indication(s) of Tetracycline

Disease Entry	ICD 11	Status	REF
Acne vulgaris	ED80	Approved	[3]
Actinomycosis	N.A.	Approved	[3]
Acute gonococcal cervicitis	N.A.	Approved	[3]
Acute gonococcal epididymo-orchitis	N.A.	Approved	[3]
Bacterial infection	1A00-1C4Z	Approved	[4]
Bronchitis	CA20	Approved	[3]
Brucellosis	N.A.	Approved	[3]
Lymphogranuloma venereum	N.A.	Approved	[3]
Ornithosis	N.A.	Approved	[3]
Pneumonia	CA40	Approved	[3]
Q fever	N.A.	Approved	[3]
Relapsing fever	N.A.	Approved	[3]
Rickettsialpox	N.A.	Approved	[3]
Rocky mountain spotted fever	N.A.	Approved	[3]
Syphilis	N.A.	Approved	[3]
Trachoma	N.A.	Approved	[3]
Typhus	N.A.	Approved	[3]
Urinary tract infection	GC08	Approved	[3]
Yaws	N.A.	Approved	[3]
Pelvic inflammatory disease	GA05	Investigative	[3]
Sinusitis	CA0A.Z	Investigative	[3]

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	[18]

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	[19]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[20]
Organic anion transporter 2 (SLC22A7)	DT0OC1Q	S22A7_HUMAN	Substrate	[21]
Organic anion transporter 3 (SLC22A8)	DTVP67E	S22A8_HUMAN	Substrate	[21]
Organic anion transporter 4 (SLC22A11)	DT06JWZ	S22AB_HUMAN	Substrate	[21]

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	[22]
Organic anion transporter 3 (SLC22A8)	OT8BY933	S22A8_HUMAN	Increases Uptake	[21]
Glutathione S-transferase P (GSTP1)	OTLP0A0Y	GSTP1_HUMAN	Decreases Activity	[23]
Glutathione S-transferase Mu 3 (GSTM3)	OTLA2WJT	GSTM3_HUMAN	Decreases Activity	[23]
Nuclear protein 1 (NUPR1)	OT4FU8C0	NUPR1_HUMAN	Increases Expression	[17]
Alpha-1-antichymotrypsin (SERPINA3)	OT9BP2S0	AACT_HUMAN	Increases Expression	[17]
Asparagine synthetase (ASNS)	OT8R922G	ASNS_HUMAN	Increases Expression	[17]
Inhibin beta E chain (INHBE)	OTOI2NYG	INHBE_HUMAN	Increases Expression	[17]
AP-1 complex subunit sigma-1A (AP1S1)	OTQ2H8DN	AP1S1_HUMAN	Decreases Expression	[17]
Transgelin (TAGLN)	OTAEZ0KP	TAGL_HUMAN	Decreases Expression	[17]
Fibronectin type III domain-containing protein 4 (FNDC4)	OTOQK0WK	FNDC4_HUMAN	Increases Expression	[17]
Protein DEPP1 (DEPP1)	OTB36PHJ	DEPP1_HUMAN	Increases Expression	[17]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Expression	[24]
Alternative prion protein (PRNP)	OTE85L1Q	APRIO_HUMAN	Affects Binding	[25]
Claudin-11 (CLDN11)	OTNN6UTL	CLD11_HUMAN	Decreases Expression	[26]
72 kDa type IV collagenase (MMP2)	OT5NIWA2	MMP2_HUMAN	Decreases Activity	[27]
Stromelysin-1 (MMP3)	OTGBI74Z	MMP3_HUMAN	Decreases Activity	[27]
Integrin alpha-5 (ITGA5)	OT3RCI67	ITA5_HUMAN	Increases Expression	[26]
Insulin-like growth factor-binding protein 1 (IGFBP1)	OT6UQV2K	IBP1_HUMAN	Increases Expression	[28]
Integrin alpha-M (ITGAM)	OTAG6HWU	ITAM_HUMAN	Decreases Expression	[26]
DNA topoisomerase 2-alpha (TOP2A)	OT6LPS08	TOP2A_HUMAN	Decreases Expression	[29]
Integrin alpha-L (ITGAL)	OTCUQAIS	ITAL_HUMAN	Decreases Expression	[26]
Neutrophil collagenase (MMP8)	OTZXH19L	MMP8_HUMAN	Decreases Activity	[27]
Integrin alpha-3 (ITGA3)	OTBCH21D	ITA3_HUMAN	Decreases Expression	[26]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[30]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[30]
Sterol regulatory element-binding protein 1 (SREBF1)	OTWBRPAI	SRBP1_HUMAN	Increases Expression	[28]
Collagenase 3 (MMP13)	OTY8BZIE	MMP13_HUMAN	Decreases Activity	[27]
Gap junction alpha-8 protein (GJA8)	OTZCPRKD	CXA8_HUMAN	Decreases Expression	[26]
Microsomal triglyceride transfer protein large subunit (MTTP)	OTNUVSDT	MTP_HUMAN	Decreases Expression	[28]
Claudin-15 (CLDN15)	OT9K0KI7	CLD15_HUMAN	Decreases Expression	[26]
Claudin-6 (CLDN6)	OTEN8ID2	CLD6_HUMAN	Decreases Expression	[26]
Claudin-8 (CLDN8)	OT7IIWXG	CLD8_HUMAN	Decreases Expression	[26]
Claudin-2 (CLDN2)	OTRF3D6Y	CLD2_HUMAN	Decreases Expression	[26]
Claudin-10 (CLDN10)	OT2CVAKY	CLD10_HUMAN	Decreases Expression	[26]
Peroxisomal bifunctional enzyme (EHHADH)	OTBAAHL5	ECHP_HUMAN	Decreases Expression	[28]
Diacylglycerol O-acyltransferase 2 (DGAT2)	OTE5PDD0	DGAT2_HUMAN	Increases Expression	[30]
Neurogenic locus notch homolog protein 4 (NOTCH4)	OTBCHB61	NOTC4_HUMAN	Decreases Expression	[26]
Angiotensin-converting enzyme 2 (ACE2)	OTTRZGU7	ACE2_HUMAN	Increases Expression	[31]
Gap junction delta-2 protein (GJD2)	OTDR288R	CXD2_HUMAN	Decreases Expression	[26]
Neurogenic locus notch homolog protein 3 (NOTCH3)	OTMVVA7F	NOTC3_HUMAN	Decreases Expression	[26]
Solute carrier family 22 member 6 (SLC22A6)	OTKRCBVM	S22A6_HUMAN	Increases Export	[21]
ATP-binding cassette sub-family C member 4 (ABCC4)	OTO27PAL	MRP4_HUMAN	Increases Transport	[32]
Organic anion transporter 7 (SLC22A9)	OTO4BJCC	S22A9_HUMAN	Increases Export	[21]

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