Details of the Drug Combination

General Information of Drug Combination (ID: DCI6WN6)

• Drug Combination Name: Anastrozole + Topotecan
• Indication: Malignant melanoma; Status: Investigative [1]
• Component Drugs:
  Anastrozole (DMNP60F): Small molecular drug
  Topotecan (DMP6G8T): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: LOX IMVI
  Zero Interaction Potency (ZIP) Score: 3.88
  Bliss Independence Score: 3.82
  Loewe Additivity Score: 6.76
  LHighest Single Agent (HSA) Score: 7.03

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Anastrozole

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Approved	[2]
Estrogen-receptor positive breast cancer	N.A.	Approved	[3]
Obesity	5B81	Approved	[3]

Anastrozole Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Aromatase (CYP19A1)	TTSZLWK	CP19A_HUMAN	Inhibitor	[8]

Anastrozole Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Putative sodium-coupled neutral amino acid transporter 7 (SLC38A7)	DT2EGUN	S38A7_HUMAN	Substrate	[9]

Anastrozole Interacts with 6 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[10]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[10]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[10]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[10]
UDP-glucuronosyltransferase 2B7 (UGT2B7)	DEB3CV1	UD2B7_HUMAN	Metabolism	[10]
UDP-glucuronosyltransferase 1A3 (UGT1A3)	DEF2WXN	UD13_HUMAN	Metabolism	[10]

Anastrozole Interacts with 6 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Adenylate kinase isoenzyme 1 (AK1)	OT614AR3	KAD1_HUMAN	Increases ADR	[11]
Progesterone receptor (PGR)	OT0FZ3QE	PRGR_HUMAN	Decreases Expression	[12]
Aromatase (CYP19A1)	OTZ6XF74	CP19A_HUMAN	Decreases Activity	[13]
NADPH--cytochrome P450 reductase (POR)	OTVIDOCH	NCPR_HUMAN	Decreases Activity	[14]
Gap junction alpha-1 protein (GJA1)	OTT94MKL	CXA1_HUMAN	Decreases Expression	[15]
Proliferation marker protein Ki-67 (MKI67)	OTA8N1QI	KI67_HUMAN	Decreases Expression	[16]

Indication(s) of Topotecan

Disease Entry	ICD 11	Status	REF
Central nervous system neoplasm	N.A.	Approved	[4]
Cervical cancer	2C77.0	Approved	[4]
Epithelial ovarian cancer	2B5D	Approved	[4]
Lung cancer	2C25.0	Approved	[4]
Ovarian cancer	2C73	Approved	[5]
Solid tumour/cancer	2A00-2F9Z	Approved	[6]
Small-cell lung cancer	2C25.Y	Phase 1	[7]
Neuroblastoma	2D11.2	Investigative	[4]

Topotecan Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
DNA topoisomerase I (TOP1)	TTGTQHC	TOP1_HUMAN	Modulator	[20]

Topotecan Interacts with 6 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 1 (ABCC1)	DTSYQGK	MRP1_HUMAN	Substrate	[21]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[22]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[23]
Multidrug and toxin extrusion protein 1 (SLC47A1)	DTZGT0P	S47A1_HUMAN	Substrate	[24]
Multidrug resistance-associated protein 4 (ABCC4)	DTCSGPB	MRP4_HUMAN	Substrate	[25]
Multidrug and toxin extrusion protein 2 (SLC47A2)	DT3TX4H	S47A2_HUMAN	Substrate	[24]

Topotecan Interacts with 246 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Expression	[26]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2)	OTW8V2V1	ABCG2_HUMAN	Decreases Response To Substance	[27]
DNA topoisomerase 2-alpha (TOP2A)	OT6LPS08	TOP2A_HUMAN	Decreases Expression	[28]
Catalase (CAT)	OTHEBX9R	CATA_HUMAN	Increases Expression	[29]
Epidermal growth factor receptor (EGFR)	OTAPLO1S	EGFR_HUMAN	Decreases Expression	[30]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Activity	[31]
Transcription factor Jun (JUN)	OTCYBO6X	JUN_HUMAN	Increases Phosphorylation	[32]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[33]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[34]
Proliferating cell nuclear antigen (PCNA)	OTHZ1RIA	PCNA_HUMAN	Decreases Expression	[30]
G2/mitotic-specific cyclin-B1 (CCNB1)	OT19S7E5	CCNB1_HUMAN	Decreases Expression	[35]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Expression	[35]
Methylated-DNA--protein-cysteine methyltransferase (MGMT)	OT40A9WH	MGMT_HUMAN	Decreases Expression	[36]
G1/S-specific cyclin-E1 (CCNE1)	OTLD7UID	CCNE1_HUMAN	Decreases Expression	[30]
Tumor necrosis factor receptor superfamily member 6 (FAS)	OTP9XG86	TNR6_HUMAN	Decreases Expression	[34]
Catenin beta-1 (CTNNB1)	OTZ932A3	CTNB1_HUMAN	Increases Cleavage	[26]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[33]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[37]
Caspase-2 (CASP2)	OTUDYSPP	CASP2_HUMAN	Increases Cleavage	[37]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[35]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Increases Activity	[26]
Hypoxia-inducible factor 1-alpha (HIF1A)	OTADSC03	HIF1A_HUMAN	Decreases Expression	[17]
ATP-binding cassette sub-family C member 2 (ABCC2)	OTJSIGV5	MRP2_HUMAN	Increases Expression	[26]
Tumor protein 63 (TP63)	OT0WOOKQ	P63_HUMAN	Decreases Expression	[35]
Bcl-2-like protein 12 (BCL2L12)	OTS6IFZY	B2L12_HUMAN	Decreases Expression	[34]
Three-prime repair exonuclease 1 (TREX1)	OTQG7K12	TREX1_HUMAN	Increases Expression	[32]
Histone H2A.V (H2AZ2)	OT0I5H2P	H2AV_HUMAN	Affects Response To Substance	[18]
Receptor-interacting serine/threonine-protein kinase 2 (RIPK2)	OT0KMIYQ	RIPK2_HUMAN	Affects Response To Substance	[18]
2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial (BCKDHA)	OT0LHOZB	ODBA_HUMAN	Affects Response To Substance	[18]
Secreted frizzled-related protein 1 (SFRP1)	OT0U9G41	SFRP1_HUMAN	Affects Response To Substance	[18]
Tripartite motif-containing protein 2 (TRIM2)	OT0V1YVC	TRIM2_HUMAN	Affects Response To Substance	[18]
Insulin-like growth factor-binding protein 7 (IGFBP7)	OT1D416P	IBP7_HUMAN	Affects Response To Substance	[18]
Tetraspanin-8 (TSPAN8)	OT1F68WQ	TSN8_HUMAN	Affects Response To Substance	[18]
Tumor necrosis factor alpha-induced protein 8 (TNFAIP8)	OT1G9297	TFIP8_HUMAN	Affects Response To Substance	[18]
Aldehyde oxidase (AOX1)	OT2FZP6H	AOXA_HUMAN	Affects Response To Substance	[18]
ATP-binding cassette sub-family D member 3 (ABCD3)	OT2PITLX	ABCD3_HUMAN	Affects Response To Substance	[18]
Optineurin (OPTN)	OT2UXWH9	OPTN_HUMAN	Affects Response To Substance	[18]
Epidermal growth factor-like protein 6 (EGFL6)	OT331X59	EGFL6_HUMAN	Decreases Response To Substance	[19]
Protein FAM171A1 (FAM171A1)	OT33BHEP	F1711_HUMAN	Affects Response To Substance	[18]
Filamin-C (FLNC)	OT3F8J6Y	FLNC_HUMAN	Affects Response To Substance	[18]
Cleavage stimulation factor subunit 2 tau variant (CSTF2T)	OT3IKRL2	CSTFT_HUMAN	Affects Response To Substance	[18]
Fatty acid CoA ligase Acsl3 (ACSL3)	OT3MWER1	ACSL3_HUMAN	Affects Response To Substance	[18]
Integrin alpha-5 (ITGA5)	OT3RCI67	ITA5_HUMAN	Affects Response To Substance	[18]
Platelet-derived growth factor C (PDGFC)	OT3ZJ0XU	PDGFC_HUMAN	Affects Response To Substance	[18]
Peptidyl-prolyl cis-trans isomerase NIMA-interacting 4 (PIN4)	OT403QC1	PIN4_HUMAN	Affects Response To Substance	[18]
C-Jun-amino-terminal kinase-interacting protein 4 (SPAG9)	OT45AHMB	JIP4_HUMAN	Affects Response To Substance	[18]
High mobility group protein B1 (HMGB1)	OT4B7CPF	HMGB1_HUMAN	Affects Response To Substance	[18]
Sorcin (SRI)	OT4R3EAC	SORCN_HUMAN	Affects Response To Substance	[18]
High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A (PDE8A)	OT4RF9Z4	PDE8A_HUMAN	Affects Response To Substance	[18]
Argininosuccinate synthase (ASS1)	OT4ZMG0Q	ASSY_HUMAN	Affects Response To Substance	[18]
Polyphosphoinositide phosphatase (FIG4)	OT501PY9	FIG4_HUMAN	Affects Response To Substance	[18]
Ubiquitin-like protein ISG15 (ISG15)	OT53QQ7N	ISG15_HUMAN	Affects Response To Substance	[18]
RAC-gamma serine/threonine-protein kinase (AKT3)	OT5M2LFI	AKT3_HUMAN	Affects Response To Substance	[18]
Leukocyte elastase inhibitor (SERPINB1)	OT5RDUFO	ILEU_HUMAN	Affects Response To Substance	[18]
Collagen alpha-2(V) chain (COL5A2)	OT5VOSQE	CO5A2_HUMAN	Decreases Response To Substance	[19]
Transcription activator BRG1 (SMARCA4)	OT68WOPQ	SMCA4_HUMAN	Affects Response To Substance	[18]
Metal cation symporter ZIP8 (SLC39A8)	OT6C6MNV	S39A8_HUMAN	Affects Response To Substance	[18]
Regulator of G-protein signaling 20 (RGS20)	OT6CGYHW	RGS20_HUMAN	Affects Response To Substance	[18]
BTB/POZ domain-containing protein KCTD3 (KCTD3)	OT6EGR42	KCTD3_HUMAN	Affects Response To Substance	[18]
Melanoma-associated antigen D1 (MAGED1)	OT6EOLFC	MAGD1_HUMAN	Affects Response To Substance	[18]
Ferritin heavy chain (FTH1)	OT6IFS0O	FRIH_HUMAN	Affects Response To Substance	[18]
Protein-glutamine gamma-glutamyltransferase 2 (TGM2)	OT6MFOWF	TGM2_HUMAN	Affects Response To Substance	[18]
G-protein-signaling modulator 2 (GPSM2)	OT6RPMRM	GPSM2_HUMAN	Affects Response To Substance	[18]
Cytochrome b5 (CYB5A)	OT6SN4RM	CYB5_HUMAN	Affects Response To Substance	[18]
Ankycorbin (RAI14)	OT6USGBK	RAI14_HUMAN	Affects Response To Substance	[18]
Plasminogen activator inhibitor 2 (SERPINB2)	OT72QLZB	PAI2_HUMAN	Affects Response To Substance	[18]
Replication protein A 70 kDa DNA-binding subunit (RPA1)	OT76POLP	RFA1_HUMAN	Affects Response To Substance	[18]
Signal transducer CD24 (CD24)	OT7CODJ4	CD24_HUMAN	Affects Response To Substance	[18]
Polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3)	OT7M67WT	GALT3_HUMAN	Affects Response To Substance	[18]
Fibroblast growth factor 2 (FGF2)	OT7YUJ9F	FGF2_HUMAN	Affects Response To Substance	[18]
Forkhead box protein D1 (FOXD1)	OT80PRHS	FOXD1_HUMAN	Affects Response To Substance	[18]
Cbp/p300-interacting transactivator 2 (CITED2)	OT812TV7	CITE2_HUMAN	Affects Response To Substance	[18]
Raftlin (RFTN1)	OT8875JE	RFTN1_HUMAN	Affects Response To Substance	[18]
Mesoderm-specific transcript homolog protein (MEST)	OT8Q4U8Y	MEST_HUMAN	Affects Response To Substance	[18]
Four-jointed box protein 1 (FJX1)	OT8SVTSS	FJX1_HUMAN	Affects Response To Substance	[18]
Leptin receptor (LEPR)	OT9H7G0C	LEPR_HUMAN	Affects Response To Substance	[18]
Calmodulin-regulated spectrin-associated protein 2 (CAMSAP2)	OT9KXWE7	CAMP2_HUMAN	Affects Response To Substance	[18]
Oxidoreductase HTATIP2 (HTATIP2)	OT9MZ4QO	HTAI2_HUMAN	Affects Response To Substance	[18]
Tissue factor pathway inhibitor (TFPI)	OTA0FX16	TFPI1_HUMAN	Affects Response To Substance	[18]
High mobility group nucleosome-binding domain-containing protein 3 (HMGN3)	OTA2TBWS	HMGN3_HUMAN	Affects Response To Substance	[18]
Diphosphoinositol polyphosphate phosphohydrolase NUDT4B (NUDT4)	OTA6ICI2	NUD4B_HUMAN	Affects Response To Substance	[18]
SEC14-like protein 1 (SEC14L1)	OTA75FET	S14L1_HUMAN	Affects Response To Substance	[18]
Autism susceptibility gene 2 protein (AUTS2)	OTAEXHSC	AUTS2_HUMAN	Affects Response To Substance	[18]
Grancalcin (GCA)	OTAJ7ZHG	GRAN_HUMAN	Affects Response To Substance	[18]
RNA polymerase II elongation factor ELL3 (ELL3)	OTALC1YD	ELL3_HUMAN	Affects Response To Substance	[18]
Receptor-type tyrosine-protein phosphatase kappa (PTPRK)	OTAP5AT3	PTPRK_HUMAN	Affects Response To Substance	[18]
snRNA-activating protein complex subunit 1 (SNAPC1)	OTAPN1NI	SNPC1_HUMAN	Affects Response To Substance	[18]
Cyclin-dependent kinase inhibitor 1C (CDKN1C)	OTASTJ3Q	CDN1C_HUMAN	Affects Response To Substance	[18]
Stearoyl-CoA desaturase (SCD)	OTB1073G	SCD_HUMAN	Affects Response To Substance	[18]
Desmoplakin (DSP)	OTB2MOP8	DESP_HUMAN	Affects Response To Substance	[18]
Protein lin-7 homolog C (LIN7C)	OTB3015O	LIN7C_HUMAN	Affects Response To Substance	[18]
Heterogeneous nuclear ribonucleoprotein D-like (HNRNPDL)	OTB3BFCV	HNRDL_HUMAN	Affects Response To Substance	[18]
High mobility group protein HMGI-C (HMGA2)	OTBMBHHL	HMGA2_HUMAN	Affects Response To Substance	[18]
Microtubule-associated tumor suppressor 1 (MTUS1)	OTBPALMU	MTUS1_HUMAN	Affects Response To Substance	[18]
Cilium assembly protein DZIP1 (DZIP1)	OTBVPO66	DZIP1_HUMAN	Affects Response To Substance	[18]
Thiamin pyrophosphokinase 1 (TPK1)	OTCHPUD0	TPK1_HUMAN	Affects Response To Substance	[18]
Cytoskeleton-associated protein 2 (CKAP2)	OTCLTC0J	CKAP2_HUMAN	Affects Response To Substance	[18]
Hydroxymethylglutaryl-CoA synthase, cytoplasmic (HMGCS1)	OTCO26FV	HMCS1_HUMAN	Affects Response To Substance	[18]
Cytochrome c oxidase copper chaperone (COX17)	OTCP4LH2	COX17_HUMAN	Affects Response To Substance	[18]
Tetraspanin-13 (TSPAN13)	OTCS9BZY	TSN13_HUMAN	Affects Response To Substance	[18]
S-phase kinase-associated protein 2 (SKP2)	OTD5B41X	SKP2_HUMAN	Affects Response To Substance	[18]
Tropomyosin alpha-1 chain (TPM1)	OTD73X6R	TPM1_HUMAN	Affects Response To Substance	[18]
Keratin, type I cytoskeletal 19 (KRT19)	OTDGDQ75	K1C19_HUMAN	Affects Response To Substance	[18]
Integrin alpha-1 (ITGA1)	OTDITIST	ITA1_HUMAN	Increases Response To Substance	[19]
AP-5 complex subunit mu-1 (AP5M1)	OTDLWEBL	AP5M1_HUMAN	Affects Response To Substance	[18]
Protein eva-1 homolog B (EVA1B)	OTDNAKQD	EVA1B_HUMAN	Affects Response To Substance	[18]
Gamma-adducin (ADD3)	OTDRSHAZ	ADDG_HUMAN	Affects Response To Substance	[18]
Dickkopf-related protein 3 (DKK3)	OTDU94EY	DKK3_HUMAN	Affects Response To Substance	[18]
Ras-related protein Rab-7L1 (RAB29)	OTDZT6LP	RAB7L_HUMAN	Affects Response To Substance	[18]
Short transient receptor potential channel 1 (TRPC1)	OTEEAGLH	TRPC1_HUMAN	Affects Response To Substance	[18]
H(+)/Cl(-) exchange transporter 3 (CLCN3)	OTEEXNMU	CLCN3_HUMAN	Affects Response To Substance	[18]
Secernin-1 (SCRN1)	OTELM5C2	SCRN1_HUMAN	Affects Response To Substance	[18]
NGFI-A-binding protein 1 (NAB1)	OTEWHIZR	NAB1_HUMAN	Affects Response To Substance	[18]
Serglycin (SRGN)	OTFAVSX0	SRGN_HUMAN	Affects Response To Substance	[18]
Solute carrier family 35 member G2 (SLC35G2)	OTFBVS0P	S35G2_HUMAN	Affects Response To Substance	[18]
Cadherin-1 (CDH1)	OTFJMXPM	CADH1_HUMAN	Affects Response To Substance	[18]
Multiple C2 and transmembrane domain-containing protein 2 (MCTP2)	OTFMZ8I2	MCTP2_HUMAN	Affects Response To Substance	[18]
Caveolae-associated protein 1 (CAVIN1)	OTFO915U	CAVN1_HUMAN	Affects Response To Substance	[18]
Laminin subunit alpha-2 (LAMA2)	OTFROQWE	LAMA2_HUMAN	Increases Response To Substance	[19]
Centriolar satellite-associated tubulin polyglutamylase complex regulator 1 (CSTPP1)	OTFSO3XV	CSTP1_HUMAN	Affects Response To Substance	[18]
Baculoviral IAP repeat-containing protein 2 (BIRC2)	OTFXFREP	BIRC2_HUMAN	Affects Response To Substance	[18]
Myelin basic protein (MBP)	OTFZCEDB	MBP_HUMAN	Affects Response To Substance	[18]
Transmembrane protein 80 (TMEM80)	OTG9D4KX	TMM80_HUMAN	Affects Response To Substance	[18]
Squalene synthase (FDFT1)	OTGDISIT	FDFT_HUMAN	Affects Response To Substance	[18]
High mobility group protein B2 (HMGB2)	OTGEGAOK	HMGB2_HUMAN	Affects Response To Substance	[18]
Cytotoxic granule associated RNA binding protein TIA1 (TIA1)	OTGPN3P8	TIA1_HUMAN	Affects Response To Substance	[18]
Stanniocalcin-1 (STC1)	OTGVVXYF	STC1_HUMAN	Affects Response To Substance	[18]
Sigma intracellular receptor 2 (TMEM97)	OTH76ZWK	SGMR2_HUMAN	Affects Response To Substance	[18]
Epithelial cell adhesion molecule (EPCAM)	OTHBZK5X	EPCAM_HUMAN	Affects Response To Substance	[18]
Delta-aminolevulinic acid dehydratase (ALAD)	OTHM9GSH	HEM2_HUMAN	Affects Response To Substance	[18]
DNA damage-inducible transcript 4 protein (DDIT4)	OTHY8SY4	DDIT4_HUMAN	Affects Response To Substance	[18]
Interstitial collagenase (MMP1)	OTI4I2V1	MMP1_HUMAN	Affects Response To Substance	[18]
Solute carrier family 38 member 6 (SLC38A6)	OTIC8SHQ	S38A6_HUMAN	Affects Response To Substance	[18]
Histone-lysine N-methyltransferase EZH2 (EZH2)	OTIEHTKW	EZH2_HUMAN	Affects Response To Substance	[18]
G2/mitotic-specific cyclin-B2 (CCNB2)	OTIEXTDK	CCNB2_HUMAN	Affects Response To Substance	[18]
Laminin subunit gamma-1 (LAMC1)	OTIG527N	LAMC1_HUMAN	Affects Response To Substance	[18]
Cyclin-G2 (CCNG2)	OTII38K2	CCNG2_HUMAN	Affects Response To Substance	[18]
Beta/gamma crystallin domain-containing protein 1 (CRYBG1)	OTIPDI15	CRBG1_HUMAN	Affects Response To Substance	[18]
Ras-related protein Rab-13 (RAB13)	OTIQ484I	RAB13_HUMAN	Affects Response To Substance	[18]
Insulin-like growth factor-binding protein 3 (IGFBP3)	OTIX63TX	IBP3_HUMAN	Affects Response To Substance	[18]
Ankyrin repeat domain-containing protein 10 (ANKRD10)	OTIZ2VK8	ANR10_HUMAN	Affects Response To Substance	[18]
Histone deacetylase complex subunit SAP18 (SAP18)	OTJAZWOL	SAP18_HUMAN	Affects Response To Substance	[18]
E3 ubiquitin-protein ligase FANCL (FANCL)	OTJC7QPQ	FANCL_HUMAN	Affects Response To Substance	[18]
Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial (HADH)	OTJDOL20	HCDH_HUMAN	Affects Response To Substance	[18]
FERM domain-containing protein 4A (FRMD4A)	OTJDTIK2	FRM4A_HUMAN	Affects Response To Substance	[18]
Cyclin-F (CCNF)	OTJFVU43	CCNF_HUMAN	Affects Response To Substance	[18]
Osteopontin (SPP1)	OTJGC23Y	OSTP_HUMAN	Affects Response To Substance	[18]
Jupiter microtubule associated homolog 2 (JPT2)	OTJGPA4T	JUPI2_HUMAN	Affects Response To Substance	[18]
TBC1 domain family member 4 (TBC1D4)	OTK66C40	TBCD4_HUMAN	Affects Response To Substance	[18]
Tumor necrosis factor receptor superfamily member 6B (TNFRSF6B)	OTKAN9G7	TNF6B_HUMAN	Affects Response To Substance	[18]
Myelin protein zero-like protein 2 (MPZL2)	OTKFNDUI	MPZL2_HUMAN	Affects Response To Substance	[18]
Transmembrane channel-like protein 6 (TMC6)	OTKH50J4	TMC6_HUMAN	Affects Response To Substance	[18]
Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2)	OTKOZRZP	PLOD2_HUMAN	Affects Response To Substance	[18]
Methylsterol monooxygenase 1 (MSMO1)	OTKV62RZ	MSMO1_HUMAN	Affects Response To Substance	[18]
Enolase-phosphatase E1 (ENOPH1)	OTKXMWNN	ENOPH_HUMAN	Affects Response To Substance	[18]
Calcium-binding tyrosine phosphorylation-regulated protein (CABYR)	OTKYMT99	CABYR_HUMAN	Affects Response To Substance	[18]
Glycylpeptide N-tetradecanoyltransferase 2 (NMT2)	OTLNA39Z	NMT2_HUMAN	Affects Response To Substance	[18]
Hemicentin-1 (HMCN1)	OTLZAS0P	HMCN1_HUMAN	Increases Response To Substance	[19]
Ribosome biogenesis protein BOP1 (BOP1)	OTMZMQDO	BOP1_HUMAN	Affects Response To Substance	[18]
Eukaryotic peptide chain release factor GTP-binding subunit ERF3B (GSPT2)	OTN0K7F3	ERF3B_HUMAN	Affects Response To Substance	[18]
Four and a half LIM domains protein 1 (FHL1)	OTN535SU	FHL1_HUMAN	Affects Response To Substance	[18]
MAP kinase-interacting serine/threonine-protein kinase 2 (MKNK2)	OTNA9G8V	MKNK2_HUMAN	Affects Response To Substance	[18]
Epithelial splicing regulatory protein 1 (ESRP1)	OTNCS4SL	ESRP1_HUMAN	Affects Response To Substance	[18]
Radixin (RDX)	OTNSYUN6	RADI_HUMAN	Affects Response To Substance	[18]
Calcium-activated potassium channel subunit alpha-1 (KCNMA1)	OTNYXOZO	KCMA1_HUMAN	Affects Response To Substance	[18]
Paraneoplastic antigen-like protein 8A (PNMA8A)	OTO3F7B0	PNM8A_HUMAN	Affects Response To Substance	[18]
Polypeptide N-acetylgalactosaminyltransferase 1 (GALNT1)	OTO3RO36	GALT1_HUMAN	Affects Response To Substance	[18]
Histone deacetylase 9 (HDAC9)	OTO8O0LF	HDAC9_HUMAN	Affects Response To Substance	[18]
Histone-lysine N-methyltransferase KMT5B (KMT5B)	OTOH7G8Q	KMT5B_HUMAN	Affects Response To Substance	[18]
BH3-interacting domain death agonist (BID)	OTOSHSHU	BID_HUMAN	Affects Response To Substance	[18]
GTP cyclohydrolase 1 (GCH1)	OTOZ6NSL	GCH1_HUMAN	Affects Response To Substance	[18]
Unconventional myosin-Id (MYO1D)	OTP2RGPN	MYO1D_HUMAN	Affects Response To Substance	[18]
Rho GTPase-activating protein 7 (DLC1)	OTP8LMCR	RHG07_HUMAN	Affects Response To Substance	[18]
Ras-related protein Rab-20 (RAB20)	OTP9OOVS	RAB20_HUMAN	Affects Response To Substance	[18]
Dual specificity protein phosphatase 3 (DUSP3)	OTPJX9B4	DUS3_HUMAN	Affects Response To Substance	[18]
DNA dC->dU-editing enzyme APOBEC-3C (APOBEC3C)	OTPL0AI1	ABC3C_HUMAN	Affects Response To Substance	[18]
Pentraxin-related protein PTX3 (PTX3)	OTPXHRKU	PTX3_HUMAN	Affects Response To Substance	[18]
Dermatan-sulfate epimerase (DSE)	OTQ108VJ	DSE_HUMAN	Affects Response To Substance	[18]
Centromere protein U (CENPU)	OTQ4TZRS	CENPU_HUMAN	Affects Response To Substance	[18]
Eukaryotic translation initiation factor 5A-1 (EIF5A)	OTQ8DJX5	IF5A1_HUMAN	Affects Response To Substance	[18]
Sortilin-related receptor (SORL1)	OTQ8FFNS	SORL_HUMAN	Affects Response To Substance	[18]
Collagen alpha-2(VI) chain (COL6A2)	OTQC6PPO	CO6A2_HUMAN	Affects Response To Substance	[18]
Ran-specific GTPase-activating protein (RANBP1)	OTQE226K	RANG_HUMAN	Affects Response To Substance	[18]
MAPK/MAK/MRK overlapping kinase (MOK)	OTQK7M9V	MOK_HUMAN	Affects Response To Substance	[18]
3-oxo-5-alpha-steroid 4-dehydrogenase 1 (SRD5A1)	OTQRET2B	S5A1_HUMAN	Affects Response To Substance	[18]
High mobility group protein HMG-I/HMG-Y (HMGA1)	OTQUSHPX	HMGA1_HUMAN	Affects Response To Substance	[18]
Keratin, type I cytoskeletal 23 (KRT23)	OTQW6UAG	K1C23_HUMAN	Increases Response To Substance	[19]
Transforming growth factor-beta-induced protein ig-h3 (TGFBI)	OTR443C5	BGH3_HUMAN	Decreases Response To Substance	[19]
Large ribosomal subunit protein mL63 (MRPL57)	OTRB659E	RT63_HUMAN	Affects Response To Substance	[18]
Actin, gamma-enteric smooth muscle (ACTG2)	OTRDWUO0	ACTH_HUMAN	Affects Response To Substance	[18]
Acidic leucine-rich nuclear phosphoprotein 32 family member A (ANP32A)	OTRHPFO2	AN32A_HUMAN	Affects Response To Substance	[18]
LIM domain kinase 2 (LIMK2)	OTRJD7VZ	LIMK2_HUMAN	Affects Response To Substance	[18]
Calcium/calmodulin-dependent protein kinase type 1 (CAMK1)	OTRN55RE	KCC1A_HUMAN	Affects Response To Substance	[18]
Receptor tyrosine-protein kinase erbB-3 (ERBB3)	OTRSST0A	ERBB3_HUMAN	Affects Response To Substance	[18]
Lysyl oxidase homolog 2 (LOXL2)	OTRT46B5	LOXL2_HUMAN	Affects Response To Substance	[18]
Arginine and glutamate-rich protein 1 (ARGLU1)	OTRVRZ4Z	ARGL1_HUMAN	Affects Response To Substance	[18]
Dr1-associated corepressor (DRAP1)	OTRWLF6D	NC2A_HUMAN	Affects Response To Substance	[18]
Latent-transforming growth factor beta-binding protein 2 (LTBP2)	OTS88GSD	LTBP2_HUMAN	Affects Response To Substance	[18]
Heat shock-related 70 kDa protein 2 (HSPA2)	OTSDET7B	HSP72_HUMAN	Affects Response To Substance	[18]
Inhibin beta A chain (INHBA)	OTSP64PQ	INHBA_HUMAN	Affects Response To Substance	[18]
Lumican (LUM)	OTSRC874	LUM_HUMAN	Decreases Response To Substance	[19]
GTP-binding protein SAR1a (SAR1A)	OTSSRVGV	SAR1A_HUMAN	Affects Response To Substance	[18]
Plasminogen activator inhibitor 1 (SERPINE1)	OTT0MPQ3	PAI1_HUMAN	Affects Response To Substance	[18]
Collagen alpha-1(III) chain (COL3A1)	OTT1EMLM	CO3A1_HUMAN	Decreases Response To Substance	[19]
DNA-binding protein SATB1 (SATB1)	OTT7SUVW	SATB1_HUMAN	Affects Response To Substance	[18]
Gap junction alpha-1 protein (GJA1)	OTT94MKL	CXA1_HUMAN	Affects Response To Substance	[18]
KH domain-containing RNA-binding protein QKI (QKI)	OTTAUGLB	QKI_HUMAN	Affects Response To Substance	[18]
Cullin-4A (CUL4A)	OTTBV70J	CUL4A_HUMAN	Affects Response To Substance	[18]
Homeobox protein Hox-B2 (HOXB2)	OTTD6HMV	HXB2_HUMAN	Affects Response To Substance	[18]
Collagen alpha-1(XV) chain (COL15A1)	OTTFKK18	COFA1_HUMAN	Decreases Response To Substance	[19]
A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1)	OTTLJH8W	ATS1_HUMAN	Affects Response To Substance	[18]
Nuclear receptor-interacting protein 3 (NRIP3)	OTU15GMK	NRIP3_HUMAN	Affects Response To Substance	[18]
Granulocyte-macrophage colony-stimulating factor receptor subunit alpha (CSF2RA)	OTUOO2XS	CSF2R_HUMAN	Affects Response To Substance	[18]
La-related protein 6 (LARP6)	OTUQ9QS9	LARP6_HUMAN	Affects Response To Substance	[18]
General transcription factor II-I (GTF2I)	OTUYL1TQ	GTF2I_HUMAN	Affects Response To Substance	[18]
Protein aurora borealis (BORA)	OTV2ZPKP	BORA_HUMAN	Affects Response To Substance	[18]
FYVE, RhoGEF and PH domain-containing protein 1 (FGD1)	OTV3T64P	FGD1_HUMAN	Affects Response To Substance	[18]
Matrilin-2 (MATN2)	OTVDR68G	MATN2_HUMAN	Decreases Response To Substance	[19]
Microtubule-actin cross-linking factor 1, isoforms 1/2/3/4/5 (MACF1)	OTVIHD77	MACF1_HUMAN	Affects Response To Substance	[18]
Serine protease FAM111A (FAM111A)	OTVLARLG	F111A_HUMAN	Affects Response To Substance	[18]
Transcription factor 7-like 2 (TCF7L2)	OTVWPZ8B	TF7L2_HUMAN	Affects Response To Substance	[18]
Interleukin-1 receptor accessory protein-like 1 (IL1RAPL1)	OTW3T4B2	IRPL1_HUMAN	Affects Response To Substance	[18]
Transcription factor E2-alpha (TCF3)	OTW6FR32	TFE2_HUMAN	Affects Response To Substance	[18]
Tissue alpha-L-fucosidase (FUCA1)	OTW71IK4	FUCO_HUMAN	Affects Response To Substance	[18]
Fanconi anemia group I protein (FANCI)	OTW8E3SC	FANCI_HUMAN	Affects Response To Substance	[18]
U2 small nuclear ribonucleoprotein A' (SNRPA1)	OTWJZFAP	RU2A_HUMAN	Affects Response To Substance	[18]
Decorin (DCN)	OTWLJL7K	PGS2_HUMAN	Decreases Response To Substance	[19]
Periostin (POSTN)	OTWP62UA	POSTN_HUMAN	Decreases Response To Substance	[19]
Methyl-CpG-binding domain protein 4 (MBD4)	OTWR9YXE	MBD4_HUMAN	Affects Response To Substance	[18]
Glypican-3 (GPC3)	OTWS8WSW	GPC3_HUMAN	Increases Response To Substance	[19]
GDP-mannose 4,6 dehydratase (GMDS)	OTWV79YD	GMDS_HUMAN	Affects Response To Substance	[18]
ORC ubiquitin ligase 1 (OBI1)	OTX62ZHW	OBI1_HUMAN	Affects Response To Substance	[18]
Caspase-6 (CASP6)	OTXLD3EC	CASP6_HUMAN	Affects Response To Substance	[18]
Condensin complex subunit 2 (NCAPH)	OTXOS97C	CND2_HUMAN	Affects Response To Substance	[18]
Collagen alpha-2(I) chain (COL1A2)	OTY7G382	CO1A2_HUMAN	Increases Response To Substance	[19]
Collagen alpha-1(VI) chain (COL6A1)	OTYKSCOB	CO6A1_HUMAN	Affects Response To Substance	[18]
Protein FAN (NSMAF)	OTYNVZ23	FAN_HUMAN	Affects Response To Substance	[18]
Protein Niban 1 (NIBAN1)	OTYOLI12	NIBA1_HUMAN	Affects Response To Substance	[18]
Nucleolar complex protein 3 homolog (NOC3L)	OTYOR3PV	NOC3L_HUMAN	Affects Response To Substance	[18]
Procathepsin L (CTSL)	OTYTUW29	CATL1_HUMAN	Affects Response To Substance	[18]
Acetyl-CoA acetyltransferase, cytosolic (ACAT2)	OTZ092ZJ	THIC_HUMAN	Affects Response To Substance	[18]
Thiosulfate sulfurtransferase (TST)	OTZ4F5LK	THTR_HUMAN	Affects Response To Substance	[18]
Tissue factor pathway inhibitor 2 (TFPI2)	OTZCRWOR	TFPI2_HUMAN	Affects Response To Substance	[18]
Insulin-induced gene 1 protein (INSIG1)	OTZF5X1D	INSI1_HUMAN	Affects Response To Substance	[18]
Suppressor of tumorigenicity 7 protein (ST7)	OTZG8RC6	ST7_HUMAN	Affects Response To Substance	[18]
Fermitin family homolog 2 (FERMT2)	OTZNPWWX	FERM2_HUMAN	Affects Response To Substance	[18]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adenocarcinoma	DCF18LA	OVCAR3	Investigative	[1]
Adult T acute lymphoblastic leukemia	DCPCEKO	MOLT-4	Investigative	[1]
Astrocytoma	DCOA4AS	SNB-19	Investigative	[1]
Clear cell renal cell carcinoma	DC5G0RH	786-0	Investigative	[1]
Cutaneous melanoma	DCDFIKF	SK-MEL-28	Investigative	[1]
Glioblastoma	DCMMNUP	SNB-75	Investigative	[1]
Glioma	DCJACL5	SF-268	Investigative	[1]
High grade ovarian serous adenocarcinoma	DC6Q7NE	OVCAR-8	Investigative	[1]
High grade ovarian serous adenocarcinoma	DCHSSPI	OVCAR-4	Investigative	[1]
High grade ovarian serous adenocarcinoma	DC4S9BS	OVCAR-5	Investigative	[1]
Lung adenocarcinoma	DCMM2B4	EKVX	Investigative	[1]
Melanoma	DCHU5QO	MALME-3M	Investigative	[1]
Melanoma	DCTNAGA	UACC-257	Investigative	[1]
Minimally invasive lung adenocarcinoma	DCWPWW3	NCI-H322M	Investigative	[1]
Mixed endometrioid and clear cell carcinoma	DCFB4IJ	IGROV1	Investigative	[1]
Ovarian serous cystadenocarcinoma	DC2DFV4	SK-OV-3	Investigative	[1]
Papillary renal cell carcinoma	DCH7W0W	ACHN	Investigative	[1]
Prostate carcinoma	DC6GXEZ	PC-3	Investigative	[1]
Renal cell carcinoma	DCMMPEX	SN12C	Investigative	[1]
Breast adenocarcinoma	DCLK1FS	MDA-MB-468	Investigative	[38]
Invasive ductal carcinoma	DCG08CI	HS 578T	Investigative	[38]

References

• [1] Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
• [2] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5137).
• [3] Anastrozole FDA Label
• [4] Topotecan FDA Label
• [5] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7101).
• [6] Plant-derived compounds in clinical trials. Drug Discov Today. 2008 Feb;13(3-4):161-71.
• [7] ClinicalTrials.gov (NCT00765973) Topotecan Liposomes Injection for Small Cell Lung Cancer (SCLC), Ovarian Cancer and Other Advanced Solid Tumors. U.S. National Institutes of Health.
• [8] Effective aromatase inhibition by anastrozole in a patient with gonadotropin-independent precocious puberty in McCune-Albright syndrome. J Pediatr Endocrinol Metab. 2002;15 Suppl 3:945-8.
• [9] Anastrozole Aromatase Inhibitor Plasma Drug Concentration Genome-Wide Association Study: Functional Epistatic Interaction Between SLC38A7 and ALPPL2. Clin Pharmacol Ther. 2019 Jan 16.
• [10] In vitro and in vivo oxidative metabolism and glucuronidation of anastrozole. Br J Clin Pharmacol. 2010 Dec;70(6):854-69.
• [11] 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.
• [12] Aromatase inhibitors: cellular and molecular effects. J Steroid Biochem Mol Biol. 2005 May;95(1-5):83-9. doi: 10.1016/j.jsbmb.2005.04.010.
• [13] Aromatase inhibition: translation into a successful therapeutic approach. Clin Cancer Res. 2005 Apr 15;11(8):2809-21. doi: 10.1158/1078-0432.CCR-04-2187.
• [14] Assessment of Five Pesticides as Endocrine-Disrupting Chemicals: Effects on Estrogen Receptors and Aromatase. Int J Environ Res Public Health. 2022 Feb 10;19(4):1959. doi: 10.3390/ijerph19041959.
• [15] Inhibition of estrogen receptor reduces connexin 43 expression in breast cancers. Toxicol Appl Pharmacol. 2018 Jan 1;338:182-190. doi: 10.1016/j.taap.2017.11.020. Epub 2017 Nov 24.
• [16] Biomarker changes during neoadjuvant anastrozole, tamoxifen, or the combination: influence of hormonal status and HER-2 in breast cancer--a study from the IMPACT trialists. J Clin Oncol. 2005 Apr 10;23(11):2477-92. doi: 10.1200/JCO.2005.07.559. Epub 2005 Mar 14.
• [17] Topotecan blocks hypoxia-inducible factor-1alpha and vascular endothelial growth factor expression induced by insulin-like growth factor-I in neuroblastoma cells. Cancer Res. 2005 Jun 1;65(11):4775-81. doi: 10.1158/0008-5472.CAN-04-3332.
• [18] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.
• [19] Microarray-based detection and expression analysis of extracellular matrix proteins in drug?resistant ovarian cancer cell lines. Oncol Rep. 2014 Nov;32(5):1981-90. doi: 10.3892/or.2014.3468. Epub 2014 Sep 9.
• [20] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [21] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [22] Involvement of P-glycoprotein, multidrug resistance protein 2 and breast cancer resistance protein in the transport of belotecan and topotecan in Caco-2 and MDCKII cells. Pharm Res. 2008 Nov;25(11):2601-12.
• [23] Differential inhibition of murine Bcrp1/Abcg2 and human BCRP/ABCG2 by the mycotoxin fumitremorgin C. Eur J Pharmacol. 2010 Oct 10;644(1-3):41-8.
• [24] Substrate specificity of MATE1 and MATE2-K, human multidrug and toxin extrusions/H(+)-organic cation antiporters. Biochem Pharmacol. 2007 Jul 15;74(2):359-71.
• [25] Topotecan is a substrate for multidrug resistance associated protein 4. Curr Drug Metab. 2006 Jan;7(1):105-18.
• [26] Chrysin blocks topotecan-induced apoptosis in Caco-2 cells in spite of inhibition of ABC-transporters. Biochem Pharmacol. 2010 Aug 15;80(4):471-9. doi: 10.1016/j.bcp.2010.04.038. Epub 2010 May 8.
• [27] Camptothecin resistance: role of the ATP-binding cassette (ABC), mitoxantrone-resistance half-transporter (MXR), and potential for glucuronidation in MXR-expressing cells. Cancer Res. 1999 Dec 1;59(23):5938-46.
• [28] Cancer cell adaptation to chemotherapy. BMC Cancer. 2005 Jul 18;5:78.
• [29] The effect of Topotecan on oxidative stress in MCF-7 human breast cancer cell line. Acta Biochim Pol. 2005;52(4):897-902.
• [30] DNA topoisomerase I is a cofactor for c-Jun in the regulation of epidermal growth factor receptor expression and cancer cell proliferation. Mol Cell Biol. 2005 Jun;25(12):5040-51. doi: 10.1128/MCB.25.12.5040-5051.2005.
• [31] Tracking the cell cycle origins for escape from topotecan action by breast cancer cells. Br J Cancer. 2003 Apr 22;88(8):1310-7. doi: 10.1038/sj.bjc.6600889.
• [32] Human three prime exonuclease TREX1 is induced by genotoxic stress and involved in protection of glioma and melanoma cells to anticancer drugs. Biochim Biophys Acta. 2013 Aug;1833(8):1832-43. doi: 10.1016/j.bbamcr.2013.03.029. Epub 2013 Apr 8.
• [33] Effect of poly(ADP-ribose)polymerase and DNA topoisomerase I inhibitors on the p53/p63-dependent survival of carcinoma cells. Biochem Pharmacol. 2015 Apr 1;94(3):212-9. doi: 10.1016/j.bcp.2015.01.012. Epub 2015 Feb 7.
• [34] Topotecan and methotrexate alter expression of the apoptosis-related genes BCL2, FAS and BCL2L12 in leukemic HL-60 cells. Biol Chem. 2006 Dec;387(12):1629-33. doi: 10.1515/BC.2006.203.
• [35] p63 involvement in poly(ADP-ribose) polymerase 1 signaling of topoisomerase I-dependent DNA damage in carcinoma cells. Biochem Pharmacol. 2013 Apr 1;85(7):999-1006. doi: 10.1016/j.bcp.2013.01.019. Epub 2013 Jan 29.
• [36] Transcriptional repression of O6-methylguanine DNA methyltransferase gene rendering cells hypersensitive to N,N'-bis(2-chloroethyl)-N-nitrosurea in camptothecin-resistant cells. Mol Pharmacol. 2008 Aug;74(2):517-26. doi: 10.1124/mol.107.043620. Epub 2008 May 20.
• [37] Topotecan triggers apoptosis in p53-deficient cells by forcing degradation of XIAP and survivin thereby activating caspase-3-mediated Bid cleavage. J Pharmacol Exp Ther. 2010 Jan;332(1):316-25. doi: 10.1124/jpet.109.159962. Epub 2009 Oct 7.
• [38] Biologically active neutrophil chemokine pattern in tonsillitis.Clin Exp Immunol. 2004 Mar;135(3):511-8. doi: 10.1111/j.1365-2249.2003.02390.x.