Details of the Drug Combination

General Information of Drug Combination (ID: DCLDV8J)

Drug Combination Name
Indazole derivative 5 Topotecan
Indication
Disease Entry Status REF
Amelanotic melanoma Investigative [1]
Component Drugs Indazole derivative 5   DMM1I8R Topotecan   DMP6G8T
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: MDA-MB-435
Zero Interaction Potency (ZIP) Score: 3.16
Bliss Independence Score: 5.57
Loewe Additivity Score: 3.36
LHighest Single Agent (HSA) Score: 5.84

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indazole derivative 5 Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
ABL T315I mutant (ABL T315I) TTZJTWA ABL1_HUMAN Inhibitor [6]
Fusion protein Bcr-Abl T315I mutant (Bcr-Abl T315I) TTIV39N BCR_HUMAN-ABL1_HUMAN Inhibitor [6]
------------------------------------------------------------------------------------
Indication(s) of Topotecan
Disease Entry ICD 11 Status REF
Central nervous system neoplasm N.A. Approved [2]
Cervical cancer 2C77.0 Approved [2]
Epithelial ovarian cancer 2B5D Approved [2]
Lung cancer 2C25.0 Approved [2]
Ovarian cancer 2C73 Approved [3]
Solid tumour/cancer 2A00-2F9Z Approved [4]
Small-cell lung cancer 2C25.Y Phase 1 [5]
Neuroblastoma 2D11.2 Investigative [2]
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 [10]
------------------------------------------------------------------------------------
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 [11]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [12]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [13]
Multidrug and toxin extrusion protein 1 (SLC47A1) DTZGT0P S47A1_HUMAN Substrate [14]
Multidrug resistance-associated protein 4 (ABCC4) DTCSGPB MRP4_HUMAN Substrate [15]
Multidrug and toxin extrusion protein 2 (SLC47A2) DT3TX4H S47A2_HUMAN Substrate [14]
------------------------------------------------------------------------------------
⏷ Show the Full List of 6 DTP(s)
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 [16]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2) OTW8V2V1 ABCG2_HUMAN Decreases Response To Substance [17]
DNA topoisomerase 2-alpha (TOP2A) OT6LPS08 TOP2A_HUMAN Decreases Expression [18]
Catalase (CAT) OTHEBX9R CATA_HUMAN Increases Expression [19]
Epidermal growth factor receptor (EGFR) OTAPLO1S EGFR_HUMAN Decreases Expression [20]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Activity [21]
Transcription factor Jun (JUN) OTCYBO6X JUN_HUMAN Increases Phosphorylation [22]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [23]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [24]
Proliferating cell nuclear antigen (PCNA) OTHZ1RIA PCNA_HUMAN Decreases Expression [20]
G2/mitotic-specific cyclin-B1 (CCNB1) OT19S7E5 CCNB1_HUMAN Decreases Expression [25]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Expression [25]
Methylated-DNA--protein-cysteine methyltransferase (MGMT) OT40A9WH MGMT_HUMAN Decreases Expression [26]
G1/S-specific cyclin-E1 (CCNE1) OTLD7UID CCNE1_HUMAN Decreases Expression [20]
Tumor necrosis factor receptor superfamily member 6 (FAS) OTP9XG86 TNR6_HUMAN Decreases Expression [24]
Catenin beta-1 (CTNNB1) OTZ932A3 CTNB1_HUMAN Increases Cleavage [16]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Increases Expression [23]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [27]
Caspase-2 (CASP2) OTUDYSPP CASP2_HUMAN Increases Cleavage [27]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [25]
Caspase-8 (CASP8) OTA8TVI8 CASP8_HUMAN Increases Activity [16]
Hypoxia-inducible factor 1-alpha (HIF1A) OTADSC03 HIF1A_HUMAN Decreases Expression [7]
ATP-binding cassette sub-family C member 2 (ABCC2) OTJSIGV5 MRP2_HUMAN Increases Expression [16]
Tumor protein 63 (TP63) OT0WOOKQ P63_HUMAN Decreases Expression [25]
Bcl-2-like protein 12 (BCL2L12) OTS6IFZY B2L12_HUMAN Decreases Expression [24]
Three-prime repair exonuclease 1 (TREX1) OTQG7K12 TREX1_HUMAN Increases Expression [22]
Histone H2A.V (H2AZ2) OT0I5H2P H2AV_HUMAN Affects Response To Substance [8]
Receptor-interacting serine/threonine-protein kinase 2 (RIPK2) OT0KMIYQ RIPK2_HUMAN Affects Response To Substance [8]
2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial (BCKDHA) OT0LHOZB ODBA_HUMAN Affects Response To Substance [8]
Secreted frizzled-related protein 1 (SFRP1) OT0U9G41 SFRP1_HUMAN Affects Response To Substance [8]
Tripartite motif-containing protein 2 (TRIM2) OT0V1YVC TRIM2_HUMAN Affects Response To Substance [8]
Insulin-like growth factor-binding protein 7 (IGFBP7) OT1D416P IBP7_HUMAN Affects Response To Substance [8]
Tetraspanin-8 (TSPAN8) OT1F68WQ TSN8_HUMAN Affects Response To Substance [8]
Tumor necrosis factor alpha-induced protein 8 (TNFAIP8) OT1G9297 TFIP8_HUMAN Affects Response To Substance [8]
Aldehyde oxidase (AOX1) OT2FZP6H AOXA_HUMAN Affects Response To Substance [8]
ATP-binding cassette sub-family D member 3 (ABCD3) OT2PITLX ABCD3_HUMAN Affects Response To Substance [8]
Optineurin (OPTN) OT2UXWH9 OPTN_HUMAN Affects Response To Substance [8]
Epidermal growth factor-like protein 6 (EGFL6) OT331X59 EGFL6_HUMAN Decreases Response To Substance [9]
Protein FAM171A1 (FAM171A1) OT33BHEP F1711_HUMAN Affects Response To Substance [8]
Filamin-C (FLNC) OT3F8J6Y FLNC_HUMAN Affects Response To Substance [8]
Cleavage stimulation factor subunit 2 tau variant (CSTF2T) OT3IKRL2 CSTFT_HUMAN Affects Response To Substance [8]
Fatty acid CoA ligase Acsl3 (ACSL3) OT3MWER1 ACSL3_HUMAN Affects Response To Substance [8]
Integrin alpha-5 (ITGA5) OT3RCI67 ITA5_HUMAN Affects Response To Substance [8]
Platelet-derived growth factor C (PDGFC) OT3ZJ0XU PDGFC_HUMAN Affects Response To Substance [8]
Peptidyl-prolyl cis-trans isomerase NIMA-interacting 4 (PIN4) OT403QC1 PIN4_HUMAN Affects Response To Substance [8]
C-Jun-amino-terminal kinase-interacting protein 4 (SPAG9) OT45AHMB JIP4_HUMAN Affects Response To Substance [8]
High mobility group protein B1 (HMGB1) OT4B7CPF HMGB1_HUMAN Affects Response To Substance [8]
Sorcin (SRI) OT4R3EAC SORCN_HUMAN Affects Response To Substance [8]
High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A (PDE8A) OT4RF9Z4 PDE8A_HUMAN Affects Response To Substance [8]
Argininosuccinate synthase (ASS1) OT4ZMG0Q ASSY_HUMAN Affects Response To Substance [8]
Polyphosphoinositide phosphatase (FIG4) OT501PY9 FIG4_HUMAN Affects Response To Substance [8]
Ubiquitin-like protein ISG15 (ISG15) OT53QQ7N ISG15_HUMAN Affects Response To Substance [8]
RAC-gamma serine/threonine-protein kinase (AKT3) OT5M2LFI AKT3_HUMAN Affects Response To Substance [8]
Leukocyte elastase inhibitor (SERPINB1) OT5RDUFO ILEU_HUMAN Affects Response To Substance [8]
Collagen alpha-2(V) chain (COL5A2) OT5VOSQE CO5A2_HUMAN Decreases Response To Substance [9]
Transcription activator BRG1 (SMARCA4) OT68WOPQ SMCA4_HUMAN Affects Response To Substance [8]
Metal cation symporter ZIP8 (SLC39A8) OT6C6MNV S39A8_HUMAN Affects Response To Substance [8]
Regulator of G-protein signaling 20 (RGS20) OT6CGYHW RGS20_HUMAN Affects Response To Substance [8]
BTB/POZ domain-containing protein KCTD3 (KCTD3) OT6EGR42 KCTD3_HUMAN Affects Response To Substance [8]
Melanoma-associated antigen D1 (MAGED1) OT6EOLFC MAGD1_HUMAN Affects Response To Substance [8]
Ferritin heavy chain (FTH1) OT6IFS0O FRIH_HUMAN Affects Response To Substance [8]
Protein-glutamine gamma-glutamyltransferase 2 (TGM2) OT6MFOWF TGM2_HUMAN Affects Response To Substance [8]
G-protein-signaling modulator 2 (GPSM2) OT6RPMRM GPSM2_HUMAN Affects Response To Substance [8]
Cytochrome b5 (CYB5A) OT6SN4RM CYB5_HUMAN Affects Response To Substance [8]
Ankycorbin (RAI14) OT6USGBK RAI14_HUMAN Affects Response To Substance [8]
Plasminogen activator inhibitor 2 (SERPINB2) OT72QLZB PAI2_HUMAN Affects Response To Substance [8]
Replication protein A 70 kDa DNA-binding subunit (RPA1) OT76POLP RFA1_HUMAN Affects Response To Substance [8]
Signal transducer CD24 (CD24) OT7CODJ4 CD24_HUMAN Affects Response To Substance [8]
Polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3) OT7M67WT GALT3_HUMAN Affects Response To Substance [8]
Fibroblast growth factor 2 (FGF2) OT7YUJ9F FGF2_HUMAN Affects Response To Substance [8]
Forkhead box protein D1 (FOXD1) OT80PRHS FOXD1_HUMAN Affects Response To Substance [8]
Cbp/p300-interacting transactivator 2 (CITED2) OT812TV7 CITE2_HUMAN Affects Response To Substance [8]
Raftlin (RFTN1) OT8875JE RFTN1_HUMAN Affects Response To Substance [8]
Mesoderm-specific transcript homolog protein (MEST) OT8Q4U8Y MEST_HUMAN Affects Response To Substance [8]
Four-jointed box protein 1 (FJX1) OT8SVTSS FJX1_HUMAN Affects Response To Substance [8]
Leptin receptor (LEPR) OT9H7G0C LEPR_HUMAN Affects Response To Substance [8]
Calmodulin-regulated spectrin-associated protein 2 (CAMSAP2) OT9KXWE7 CAMP2_HUMAN Affects Response To Substance [8]
Oxidoreductase HTATIP2 (HTATIP2) OT9MZ4QO HTAI2_HUMAN Affects Response To Substance [8]
Tissue factor pathway inhibitor (TFPI) OTA0FX16 TFPI1_HUMAN Affects Response To Substance [8]
High mobility group nucleosome-binding domain-containing protein 3 (HMGN3) OTA2TBWS HMGN3_HUMAN Affects Response To Substance [8]
Diphosphoinositol polyphosphate phosphohydrolase NUDT4B (NUDT4) OTA6ICI2 NUD4B_HUMAN Affects Response To Substance [8]
SEC14-like protein 1 (SEC14L1) OTA75FET S14L1_HUMAN Affects Response To Substance [8]
Autism susceptibility gene 2 protein (AUTS2) OTAEXHSC AUTS2_HUMAN Affects Response To Substance [8]
Grancalcin (GCA) OTAJ7ZHG GRAN_HUMAN Affects Response To Substance [8]
RNA polymerase II elongation factor ELL3 (ELL3) OTALC1YD ELL3_HUMAN Affects Response To Substance [8]
Receptor-type tyrosine-protein phosphatase kappa (PTPRK) OTAP5AT3 PTPRK_HUMAN Affects Response To Substance [8]
snRNA-activating protein complex subunit 1 (SNAPC1) OTAPN1NI SNPC1_HUMAN Affects Response To Substance [8]
Cyclin-dependent kinase inhibitor 1C (CDKN1C) OTASTJ3Q CDN1C_HUMAN Affects Response To Substance [8]
Stearoyl-CoA desaturase (SCD) OTB1073G SCD_HUMAN Affects Response To Substance [8]
Desmoplakin (DSP) OTB2MOP8 DESP_HUMAN Affects Response To Substance [8]
Protein lin-7 homolog C (LIN7C) OTB3015O LIN7C_HUMAN Affects Response To Substance [8]
Heterogeneous nuclear ribonucleoprotein D-like (HNRNPDL) OTB3BFCV HNRDL_HUMAN Affects Response To Substance [8]
High mobility group protein HMGI-C (HMGA2) OTBMBHHL HMGA2_HUMAN Affects Response To Substance [8]
Microtubule-associated tumor suppressor 1 (MTUS1) OTBPALMU MTUS1_HUMAN Affects Response To Substance [8]
Cilium assembly protein DZIP1 (DZIP1) OTBVPO66 DZIP1_HUMAN Affects Response To Substance [8]
Thiamin pyrophosphokinase 1 (TPK1) OTCHPUD0 TPK1_HUMAN Affects Response To Substance [8]
Cytoskeleton-associated protein 2 (CKAP2) OTCLTC0J CKAP2_HUMAN Affects Response To Substance [8]
Hydroxymethylglutaryl-CoA synthase, cytoplasmic (HMGCS1) OTCO26FV HMCS1_HUMAN Affects Response To Substance [8]
Cytochrome c oxidase copper chaperone (COX17) OTCP4LH2 COX17_HUMAN Affects Response To Substance [8]
Tetraspanin-13 (TSPAN13) OTCS9BZY TSN13_HUMAN Affects Response To Substance [8]
S-phase kinase-associated protein 2 (SKP2) OTD5B41X SKP2_HUMAN Affects Response To Substance [8]
Tropomyosin alpha-1 chain (TPM1) OTD73X6R TPM1_HUMAN Affects Response To Substance [8]
Keratin, type I cytoskeletal 19 (KRT19) OTDGDQ75 K1C19_HUMAN Affects Response To Substance [8]
Integrin alpha-1 (ITGA1) OTDITIST ITA1_HUMAN Increases Response To Substance [9]
AP-5 complex subunit mu-1 (AP5M1) OTDLWEBL AP5M1_HUMAN Affects Response To Substance [8]
Protein eva-1 homolog B (EVA1B) OTDNAKQD EVA1B_HUMAN Affects Response To Substance [8]
Gamma-adducin (ADD3) OTDRSHAZ ADDG_HUMAN Affects Response To Substance [8]
Dickkopf-related protein 3 (DKK3) OTDU94EY DKK3_HUMAN Affects Response To Substance [8]
Ras-related protein Rab-7L1 (RAB29) OTDZT6LP RAB7L_HUMAN Affects Response To Substance [8]
Short transient receptor potential channel 1 (TRPC1) OTEEAGLH TRPC1_HUMAN Affects Response To Substance [8]
H(+)/Cl(-) exchange transporter 3 (CLCN3) OTEEXNMU CLCN3_HUMAN Affects Response To Substance [8]
Secernin-1 (SCRN1) OTELM5C2 SCRN1_HUMAN Affects Response To Substance [8]
NGFI-A-binding protein 1 (NAB1) OTEWHIZR NAB1_HUMAN Affects Response To Substance [8]
Serglycin (SRGN) OTFAVSX0 SRGN_HUMAN Affects Response To Substance [8]
Solute carrier family 35 member G2 (SLC35G2) OTFBVS0P S35G2_HUMAN Affects Response To Substance [8]
Cadherin-1 (CDH1) OTFJMXPM CADH1_HUMAN Affects Response To Substance [8]
Multiple C2 and transmembrane domain-containing protein 2 (MCTP2) OTFMZ8I2 MCTP2_HUMAN Affects Response To Substance [8]
Caveolae-associated protein 1 (CAVIN1) OTFO915U CAVN1_HUMAN Affects Response To Substance [8]
Laminin subunit alpha-2 (LAMA2) OTFROQWE LAMA2_HUMAN Increases Response To Substance [9]
Centriolar satellite-associated tubulin polyglutamylase complex regulator 1 (CSTPP1) OTFSO3XV CSTP1_HUMAN Affects Response To Substance [8]
Baculoviral IAP repeat-containing protein 2 (BIRC2) OTFXFREP BIRC2_HUMAN Affects Response To Substance [8]
Myelin basic protein (MBP) OTFZCEDB MBP_HUMAN Affects Response To Substance [8]
Transmembrane protein 80 (TMEM80) OTG9D4KX TMM80_HUMAN Affects Response To Substance [8]
Squalene synthase (FDFT1) OTGDISIT FDFT_HUMAN Affects Response To Substance [8]
High mobility group protein B2 (HMGB2) OTGEGAOK HMGB2_HUMAN Affects Response To Substance [8]
Cytotoxic granule associated RNA binding protein TIA1 (TIA1) OTGPN3P8 TIA1_HUMAN Affects Response To Substance [8]
Stanniocalcin-1 (STC1) OTGVVXYF STC1_HUMAN Affects Response To Substance [8]
Sigma intracellular receptor 2 (TMEM97) OTH76ZWK SGMR2_HUMAN Affects Response To Substance [8]
Epithelial cell adhesion molecule (EPCAM) OTHBZK5X EPCAM_HUMAN Affects Response To Substance [8]
Delta-aminolevulinic acid dehydratase (ALAD) OTHM9GSH HEM2_HUMAN Affects Response To Substance [8]
DNA damage-inducible transcript 4 protein (DDIT4) OTHY8SY4 DDIT4_HUMAN Affects Response To Substance [8]
Interstitial collagenase (MMP1) OTI4I2V1 MMP1_HUMAN Affects Response To Substance [8]
Solute carrier family 38 member 6 (SLC38A6) OTIC8SHQ S38A6_HUMAN Affects Response To Substance [8]
Histone-lysine N-methyltransferase EZH2 (EZH2) OTIEHTKW EZH2_HUMAN Affects Response To Substance [8]
G2/mitotic-specific cyclin-B2 (CCNB2) OTIEXTDK CCNB2_HUMAN Affects Response To Substance [8]
Laminin subunit gamma-1 (LAMC1) OTIG527N LAMC1_HUMAN Affects Response To Substance [8]
Cyclin-G2 (CCNG2) OTII38K2 CCNG2_HUMAN Affects Response To Substance [8]
Beta/gamma crystallin domain-containing protein 1 (CRYBG1) OTIPDI15 CRBG1_HUMAN Affects Response To Substance [8]
Ras-related protein Rab-13 (RAB13) OTIQ484I RAB13_HUMAN Affects Response To Substance [8]
Insulin-like growth factor-binding protein 3 (IGFBP3) OTIX63TX IBP3_HUMAN Affects Response To Substance [8]
Ankyrin repeat domain-containing protein 10 (ANKRD10) OTIZ2VK8 ANR10_HUMAN Affects Response To Substance [8]
Histone deacetylase complex subunit SAP18 (SAP18) OTJAZWOL SAP18_HUMAN Affects Response To Substance [8]
E3 ubiquitin-protein ligase FANCL (FANCL) OTJC7QPQ FANCL_HUMAN Affects Response To Substance [8]
Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial (HADH) OTJDOL20 HCDH_HUMAN Affects Response To Substance [8]
FERM domain-containing protein 4A (FRMD4A) OTJDTIK2 FRM4A_HUMAN Affects Response To Substance [8]
Cyclin-F (CCNF) OTJFVU43 CCNF_HUMAN Affects Response To Substance [8]
Osteopontin (SPP1) OTJGC23Y OSTP_HUMAN Affects Response To Substance [8]
Jupiter microtubule associated homolog 2 (JPT2) OTJGPA4T JUPI2_HUMAN Affects Response To Substance [8]
TBC1 domain family member 4 (TBC1D4) OTK66C40 TBCD4_HUMAN Affects Response To Substance [8]
Tumor necrosis factor receptor superfamily member 6B (TNFRSF6B) OTKAN9G7 TNF6B_HUMAN Affects Response To Substance [8]
Myelin protein zero-like protein 2 (MPZL2) OTKFNDUI MPZL2_HUMAN Affects Response To Substance [8]
Transmembrane channel-like protein 6 (TMC6) OTKH50J4 TMC6_HUMAN Affects Response To Substance [8]
Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2) OTKOZRZP PLOD2_HUMAN Affects Response To Substance [8]
Methylsterol monooxygenase 1 (MSMO1) OTKV62RZ MSMO1_HUMAN Affects Response To Substance [8]
Enolase-phosphatase E1 (ENOPH1) OTKXMWNN ENOPH_HUMAN Affects Response To Substance [8]
Calcium-binding tyrosine phosphorylation-regulated protein (CABYR) OTKYMT99 CABYR_HUMAN Affects Response To Substance [8]
Glycylpeptide N-tetradecanoyltransferase 2 (NMT2) OTLNA39Z NMT2_HUMAN Affects Response To Substance [8]
Hemicentin-1 (HMCN1) OTLZAS0P HMCN1_HUMAN Increases Response To Substance [9]
Ribosome biogenesis protein BOP1 (BOP1) OTMZMQDO BOP1_HUMAN Affects Response To Substance [8]
Eukaryotic peptide chain release factor GTP-binding subunit ERF3B (GSPT2) OTN0K7F3 ERF3B_HUMAN Affects Response To Substance [8]
Four and a half LIM domains protein 1 (FHL1) OTN535SU FHL1_HUMAN Affects Response To Substance [8]
MAP kinase-interacting serine/threonine-protein kinase 2 (MKNK2) OTNA9G8V MKNK2_HUMAN Affects Response To Substance [8]
Epithelial splicing regulatory protein 1 (ESRP1) OTNCS4SL ESRP1_HUMAN Affects Response To Substance [8]
Radixin (RDX) OTNSYUN6 RADI_HUMAN Affects Response To Substance [8]
Calcium-activated potassium channel subunit alpha-1 (KCNMA1) OTNYXOZO KCMA1_HUMAN Affects Response To Substance [8]
Paraneoplastic antigen-like protein 8A (PNMA8A) OTO3F7B0 PNM8A_HUMAN Affects Response To Substance [8]
Polypeptide N-acetylgalactosaminyltransferase 1 (GALNT1) OTO3RO36 GALT1_HUMAN Affects Response To Substance [8]
Histone deacetylase 9 (HDAC9) OTO8O0LF HDAC9_HUMAN Affects Response To Substance [8]
Histone-lysine N-methyltransferase KMT5B (KMT5B) OTOH7G8Q KMT5B_HUMAN Affects Response To Substance [8]
BH3-interacting domain death agonist (BID) OTOSHSHU BID_HUMAN Affects Response To Substance [8]
GTP cyclohydrolase 1 (GCH1) OTOZ6NSL GCH1_HUMAN Affects Response To Substance [8]
Unconventional myosin-Id (MYO1D) OTP2RGPN MYO1D_HUMAN Affects Response To Substance [8]
Rho GTPase-activating protein 7 (DLC1) OTP8LMCR RHG07_HUMAN Affects Response To Substance [8]
Ras-related protein Rab-20 (RAB20) OTP9OOVS RAB20_HUMAN Affects Response To Substance [8]
Dual specificity protein phosphatase 3 (DUSP3) OTPJX9B4 DUS3_HUMAN Affects Response To Substance [8]
DNA dC->dU-editing enzyme APOBEC-3C (APOBEC3C) OTPL0AI1 ABC3C_HUMAN Affects Response To Substance [8]
Pentraxin-related protein PTX3 (PTX3) OTPXHRKU PTX3_HUMAN Affects Response To Substance [8]
Dermatan-sulfate epimerase (DSE) OTQ108VJ DSE_HUMAN Affects Response To Substance [8]
Centromere protein U (CENPU) OTQ4TZRS CENPU_HUMAN Affects Response To Substance [8]
Eukaryotic translation initiation factor 5A-1 (EIF5A) OTQ8DJX5 IF5A1_HUMAN Affects Response To Substance [8]
Sortilin-related receptor (SORL1) OTQ8FFNS SORL_HUMAN Affects Response To Substance [8]
Collagen alpha-2(VI) chain (COL6A2) OTQC6PPO CO6A2_HUMAN Affects Response To Substance [8]
Ran-specific GTPase-activating protein (RANBP1) OTQE226K RANG_HUMAN Affects Response To Substance [8]
MAPK/MAK/MRK overlapping kinase (MOK) OTQK7M9V MOK_HUMAN Affects Response To Substance [8]
3-oxo-5-alpha-steroid 4-dehydrogenase 1 (SRD5A1) OTQRET2B S5A1_HUMAN Affects Response To Substance [8]
High mobility group protein HMG-I/HMG-Y (HMGA1) OTQUSHPX HMGA1_HUMAN Affects Response To Substance [8]
Keratin, type I cytoskeletal 23 (KRT23) OTQW6UAG K1C23_HUMAN Increases Response To Substance [9]
Transforming growth factor-beta-induced protein ig-h3 (TGFBI) OTR443C5 BGH3_HUMAN Decreases Response To Substance [9]
Large ribosomal subunit protein mL63 (MRPL57) OTRB659E RT63_HUMAN Affects Response To Substance [8]
Actin, gamma-enteric smooth muscle (ACTG2) OTRDWUO0 ACTH_HUMAN Affects Response To Substance [8]
Acidic leucine-rich nuclear phosphoprotein 32 family member A (ANP32A) OTRHPFO2 AN32A_HUMAN Affects Response To Substance [8]
LIM domain kinase 2 (LIMK2) OTRJD7VZ LIMK2_HUMAN Affects Response To Substance [8]
Calcium/calmodulin-dependent protein kinase type 1 (CAMK1) OTRN55RE KCC1A_HUMAN Affects Response To Substance [8]
Receptor tyrosine-protein kinase erbB-3 (ERBB3) OTRSST0A ERBB3_HUMAN Affects Response To Substance [8]
Lysyl oxidase homolog 2 (LOXL2) OTRT46B5 LOXL2_HUMAN Affects Response To Substance [8]
Arginine and glutamate-rich protein 1 (ARGLU1) OTRVRZ4Z ARGL1_HUMAN Affects Response To Substance [8]
Dr1-associated corepressor (DRAP1) OTRWLF6D NC2A_HUMAN Affects Response To Substance [8]
Latent-transforming growth factor beta-binding protein 2 (LTBP2) OTS88GSD LTBP2_HUMAN Affects Response To Substance [8]
Heat shock-related 70 kDa protein 2 (HSPA2) OTSDET7B HSP72_HUMAN Affects Response To Substance [8]
Inhibin beta A chain (INHBA) OTSP64PQ INHBA_HUMAN Affects Response To Substance [8]
Lumican (LUM) OTSRC874 LUM_HUMAN Decreases Response To Substance [9]
GTP-binding protein SAR1a (SAR1A) OTSSRVGV SAR1A_HUMAN Affects Response To Substance [8]
Plasminogen activator inhibitor 1 (SERPINE1) OTT0MPQ3 PAI1_HUMAN Affects Response To Substance [8]
Collagen alpha-1(III) chain (COL3A1) OTT1EMLM CO3A1_HUMAN Decreases Response To Substance [9]
DNA-binding protein SATB1 (SATB1) OTT7SUVW SATB1_HUMAN Affects Response To Substance [8]
Gap junction alpha-1 protein (GJA1) OTT94MKL CXA1_HUMAN Affects Response To Substance [8]
KH domain-containing RNA-binding protein QKI (QKI) OTTAUGLB QKI_HUMAN Affects Response To Substance [8]
Cullin-4A (CUL4A) OTTBV70J CUL4A_HUMAN Affects Response To Substance [8]
Homeobox protein Hox-B2 (HOXB2) OTTD6HMV HXB2_HUMAN Affects Response To Substance [8]
Collagen alpha-1(XV) chain (COL15A1) OTTFKK18 COFA1_HUMAN Decreases Response To Substance [9]
A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1) OTTLJH8W ATS1_HUMAN Affects Response To Substance [8]
Nuclear receptor-interacting protein 3 (NRIP3) OTU15GMK NRIP3_HUMAN Affects Response To Substance [8]
Granulocyte-macrophage colony-stimulating factor receptor subunit alpha (CSF2RA) OTUOO2XS CSF2R_HUMAN Affects Response To Substance [8]
La-related protein 6 (LARP6) OTUQ9QS9 LARP6_HUMAN Affects Response To Substance [8]
General transcription factor II-I (GTF2I) OTUYL1TQ GTF2I_HUMAN Affects Response To Substance [8]
Protein aurora borealis (BORA) OTV2ZPKP BORA_HUMAN Affects Response To Substance [8]
FYVE, RhoGEF and PH domain-containing protein 1 (FGD1) OTV3T64P FGD1_HUMAN Affects Response To Substance [8]
Matrilin-2 (MATN2) OTVDR68G MATN2_HUMAN Decreases Response To Substance [9]
Microtubule-actin cross-linking factor 1, isoforms 1/2/3/4/5 (MACF1) OTVIHD77 MACF1_HUMAN Affects Response To Substance [8]
Serine protease FAM111A (FAM111A) OTVLARLG F111A_HUMAN Affects Response To Substance [8]
Transcription factor 7-like 2 (TCF7L2) OTVWPZ8B TF7L2_HUMAN Affects Response To Substance [8]
Interleukin-1 receptor accessory protein-like 1 (IL1RAPL1) OTW3T4B2 IRPL1_HUMAN Affects Response To Substance [8]
Transcription factor E2-alpha (TCF3) OTW6FR32 TFE2_HUMAN Affects Response To Substance [8]
Tissue alpha-L-fucosidase (FUCA1) OTW71IK4 FUCO_HUMAN Affects Response To Substance [8]
Fanconi anemia group I protein (FANCI) OTW8E3SC FANCI_HUMAN Affects Response To Substance [8]
U2 small nuclear ribonucleoprotein A' (SNRPA1) OTWJZFAP RU2A_HUMAN Affects Response To Substance [8]
Decorin (DCN) OTWLJL7K PGS2_HUMAN Decreases Response To Substance [9]
Periostin (POSTN) OTWP62UA POSTN_HUMAN Decreases Response To Substance [9]
Methyl-CpG-binding domain protein 4 (MBD4) OTWR9YXE MBD4_HUMAN Affects Response To Substance [8]
Glypican-3 (GPC3) OTWS8WSW GPC3_HUMAN Increases Response To Substance [9]
GDP-mannose 4,6 dehydratase (GMDS) OTWV79YD GMDS_HUMAN Affects Response To Substance [8]
ORC ubiquitin ligase 1 (OBI1) OTX62ZHW OBI1_HUMAN Affects Response To Substance [8]
Caspase-6 (CASP6) OTXLD3EC CASP6_HUMAN Affects Response To Substance [8]
Condensin complex subunit 2 (NCAPH) OTXOS97C CND2_HUMAN Affects Response To Substance [8]
Collagen alpha-2(I) chain (COL1A2) OTY7G382 CO1A2_HUMAN Increases Response To Substance [9]
Collagen alpha-1(VI) chain (COL6A1) OTYKSCOB CO6A1_HUMAN Affects Response To Substance [8]
Protein FAN (NSMAF) OTYNVZ23 FAN_HUMAN Affects Response To Substance [8]
Protein Niban 1 (NIBAN1) OTYOLI12 NIBA1_HUMAN Affects Response To Substance [8]
Nucleolar complex protein 3 homolog (NOC3L) OTYOR3PV NOC3L_HUMAN Affects Response To Substance [8]
Procathepsin L (CTSL) OTYTUW29 CATL1_HUMAN Affects Response To Substance [8]
Acetyl-CoA acetyltransferase, cytosolic (ACAT2) OTZ092ZJ THIC_HUMAN Affects Response To Substance [8]
Thiosulfate sulfurtransferase (TST) OTZ4F5LK THTR_HUMAN Affects Response To Substance [8]
Tissue factor pathway inhibitor 2 (TFPI2) OTZCRWOR TFPI2_HUMAN Affects Response To Substance [8]
Insulin-induced gene 1 protein (INSIG1) OTZF5X1D INSI1_HUMAN Affects Response To Substance [8]
Suppressor of tumorigenicity 7 protein (ST7) OTZG8RC6 ST7_HUMAN Affects Response To Substance [8]
Fermitin family homolog 2 (FERMT2) OTZNPWWX FERM2_HUMAN Affects Response To Substance [8]
------------------------------------------------------------------------------------
⏷ Show the Full List of 246 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Adult T acute lymphoblastic leukemia DCON5CJ MOLT-4 Investigative [28]
Clear cell renal cell carcinoma DC9YGCX TK-10 Investigative [28]
Clear cell renal cell carcinoma DC2BNOM CAKI-1 Investigative [28]
Glioma DCMFRR2 SF-268 Investigative [28]
Papillary renal cell carcinoma DCWJQ5B ACHN Investigative [28]
Breast adenocarcinoma DCN3EKC MDA-MB-468 Investigative [29]
Carcinoma DCT3KZB MCF7 Investigative [29]
Invasive ductal carcinoma DCZY7A4 BT-549 Investigative [29]
Cutaneous melanoma DCMBLB9 SK-MEL-28 Investigative [1]
High grade ovarian serous adenocarcinoma DC2XWA1 OVCAR-8 Investigative [1]
High grade ovarian serous adenocarcinoma DCD3UP4 OVCAR-5 Investigative [1]
Lung adenocarcinoma DCXTOD2 MDA-MB-231 Investigative [1]
Melanoma DC47JNC MALME-3M Investigative [1]
Melanoma DCMC289 UACC-257 Investigative [1]
Minimally invasive lung adenocarcinoma DC8FJ3G NCI-H322M Investigative [1]
Mixed endometrioid and clear cell carcinoma DCFCJWW IGROV1 Investigative [1]
Pleural epithelioid mesothelioma DCY64ET NCI-H226 Investigative [1]
Prostate carcinoma DCCQXYW PC-3 Investigative [1]
------------------------------------------------------------------------------------
⏷ Show the Full List of 18 DrugCom(s)

References

1 Loss of function mutations in VARS encoding cytoplasmic valyl-tRNA synthetase cause microcephaly, seizures, and progressive cerebral atrophy.Hum Genet. 2018 Apr;137(4):293-303. doi: 10.1007/s00439-018-1882-3. Epub 2018 Apr 24.
2 Topotecan FDA Label
3 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).
4 Plant-derived compounds in clinical trials. Drug Discov Today. 2008 Feb;13(3-4):161-71.
5 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.
6 Bcr-Abl tyrosine kinase inhibitors: a patent review.Expert Opin Ther Pat. 2015 Apr;25(4):397-412.
7 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.
8 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.
9 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.
10 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
11 Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
12 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.
13 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.
14 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.
15 Topotecan is a substrate for multidrug resistance associated protein 4. Curr Drug Metab. 2006 Jan;7(1):105-18.
16 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.
17 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.
18 Cancer cell adaptation to chemotherapy. BMC Cancer. 2005 Jul 18;5:78.
19 The effect of Topotecan on oxidative stress in MCF-7 human breast cancer cell line. Acta Biochim Pol. 2005;52(4):897-902.
20 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.
21 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.
22 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.
23 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.
24 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.
25 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.
26 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.
27 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.
28 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.
29 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.