General Information of Drug Combination (ID: DC1CO3X)

Drug Combination Name
Topotecan MK-2206
Indication
Disease Entry Status REF
Breast and ovarian cancer syndrome Investigative [1]
Component Drugs Topotecan   DMP6G8T MK-2206   DMT1OZ6
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: UWB1289
Zero Interaction Potency (ZIP) Score: 1.21
Bliss Independence Score: 3.28
Loewe Additivity Score: 10.14
LHighest Single Agent (HSA) Score: 12.31

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
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 [11]
------------------------------------------------------------------------------------
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 [12]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [13]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [14]
Multidrug and toxin extrusion protein 1 (SLC47A1) DTZGT0P S47A1_HUMAN Substrate [15]
Multidrug resistance-associated protein 4 (ABCC4) DTCSGPB MRP4_HUMAN Substrate [16]
Multidrug and toxin extrusion protein 2 (SLC47A2) DT3TX4H S47A2_HUMAN Substrate [15]
------------------------------------------------------------------------------------
⏷ 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 [17]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2) OTW8V2V1 ABCG2_HUMAN Decreases Response To Substance [18]
DNA topoisomerase 2-alpha (TOP2A) OT6LPS08 TOP2A_HUMAN Decreases Expression [19]
Catalase (CAT) OTHEBX9R CATA_HUMAN Increases Expression [20]
Epidermal growth factor receptor (EGFR) OTAPLO1S EGFR_HUMAN Decreases Expression [21]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Activity [22]
Transcription factor Jun (JUN) OTCYBO6X JUN_HUMAN Increases Phosphorylation [23]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [24]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [25]
Proliferating cell nuclear antigen (PCNA) OTHZ1RIA PCNA_HUMAN Decreases Expression [21]
G2/mitotic-specific cyclin-B1 (CCNB1) OT19S7E5 CCNB1_HUMAN Decreases Expression [26]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Expression [26]
Methylated-DNA--protein-cysteine methyltransferase (MGMT) OT40A9WH MGMT_HUMAN Decreases Expression [27]
G1/S-specific cyclin-E1 (CCNE1) OTLD7UID CCNE1_HUMAN Decreases Expression [21]
Tumor necrosis factor receptor superfamily member 6 (FAS) OTP9XG86 TNR6_HUMAN Decreases Expression [25]
Catenin beta-1 (CTNNB1) OTZ932A3 CTNB1_HUMAN Increases Cleavage [17]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Increases Expression [24]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [28]
Caspase-2 (CASP2) OTUDYSPP CASP2_HUMAN Increases Cleavage [28]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [26]
Caspase-8 (CASP8) OTA8TVI8 CASP8_HUMAN Increases Activity [17]
Hypoxia-inducible factor 1-alpha (HIF1A) OTADSC03 HIF1A_HUMAN Decreases Expression [8]
ATP-binding cassette sub-family C member 2 (ABCC2) OTJSIGV5 MRP2_HUMAN Increases Expression [17]
Tumor protein 63 (TP63) OT0WOOKQ P63_HUMAN Decreases Expression [26]
Bcl-2-like protein 12 (BCL2L12) OTS6IFZY B2L12_HUMAN Decreases Expression [25]
Three-prime repair exonuclease 1 (TREX1) OTQG7K12 TREX1_HUMAN Increases Expression [23]
Histone H2A.V (H2AZ2) OT0I5H2P H2AV_HUMAN Affects Response To Substance [9]
Receptor-interacting serine/threonine-protein kinase 2 (RIPK2) OT0KMIYQ RIPK2_HUMAN Affects Response To Substance [9]
2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial (BCKDHA) OT0LHOZB ODBA_HUMAN Affects Response To Substance [9]
Secreted frizzled-related protein 1 (SFRP1) OT0U9G41 SFRP1_HUMAN Affects Response To Substance [9]
Tripartite motif-containing protein 2 (TRIM2) OT0V1YVC TRIM2_HUMAN Affects Response To Substance [9]
Insulin-like growth factor-binding protein 7 (IGFBP7) OT1D416P IBP7_HUMAN Affects Response To Substance [9]
Tetraspanin-8 (TSPAN8) OT1F68WQ TSN8_HUMAN Affects Response To Substance [9]
Tumor necrosis factor alpha-induced protein 8 (TNFAIP8) OT1G9297 TFIP8_HUMAN Affects Response To Substance [9]
Aldehyde oxidase (AOX1) OT2FZP6H AOXA_HUMAN Affects Response To Substance [9]
ATP-binding cassette sub-family D member 3 (ABCD3) OT2PITLX ABCD3_HUMAN Affects Response To Substance [9]
Optineurin (OPTN) OT2UXWH9 OPTN_HUMAN Affects Response To Substance [9]
Epidermal growth factor-like protein 6 (EGFL6) OT331X59 EGFL6_HUMAN Decreases Response To Substance [10]
Protein FAM171A1 (FAM171A1) OT33BHEP F1711_HUMAN Affects Response To Substance [9]
Filamin-C (FLNC) OT3F8J6Y FLNC_HUMAN Affects Response To Substance [9]
Cleavage stimulation factor subunit 2 tau variant (CSTF2T) OT3IKRL2 CSTFT_HUMAN Affects Response To Substance [9]
Fatty acid CoA ligase Acsl3 (ACSL3) OT3MWER1 ACSL3_HUMAN Affects Response To Substance [9]
Integrin alpha-5 (ITGA5) OT3RCI67 ITA5_HUMAN Affects Response To Substance [9]
Platelet-derived growth factor C (PDGFC) OT3ZJ0XU PDGFC_HUMAN Affects Response To Substance [9]
Peptidyl-prolyl cis-trans isomerase NIMA-interacting 4 (PIN4) OT403QC1 PIN4_HUMAN Affects Response To Substance [9]
C-Jun-amino-terminal kinase-interacting protein 4 (SPAG9) OT45AHMB JIP4_HUMAN Affects Response To Substance [9]
High mobility group protein B1 (HMGB1) OT4B7CPF HMGB1_HUMAN Affects Response To Substance [9]
Sorcin (SRI) OT4R3EAC SORCN_HUMAN Affects Response To Substance [9]
High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A (PDE8A) OT4RF9Z4 PDE8A_HUMAN Affects Response To Substance [9]
Argininosuccinate synthase (ASS1) OT4ZMG0Q ASSY_HUMAN Affects Response To Substance [9]
Polyphosphoinositide phosphatase (FIG4) OT501PY9 FIG4_HUMAN Affects Response To Substance [9]
Ubiquitin-like protein ISG15 (ISG15) OT53QQ7N ISG15_HUMAN Affects Response To Substance [9]
RAC-gamma serine/threonine-protein kinase (AKT3) OT5M2LFI AKT3_HUMAN Affects Response To Substance [9]
Leukocyte elastase inhibitor (SERPINB1) OT5RDUFO ILEU_HUMAN Affects Response To Substance [9]
Collagen alpha-2(V) chain (COL5A2) OT5VOSQE CO5A2_HUMAN Decreases Response To Substance [10]
Transcription activator BRG1 (SMARCA4) OT68WOPQ SMCA4_HUMAN Affects Response To Substance [9]
Metal cation symporter ZIP8 (SLC39A8) OT6C6MNV S39A8_HUMAN Affects Response To Substance [9]
Regulator of G-protein signaling 20 (RGS20) OT6CGYHW RGS20_HUMAN Affects Response To Substance [9]
BTB/POZ domain-containing protein KCTD3 (KCTD3) OT6EGR42 KCTD3_HUMAN Affects Response To Substance [9]
Melanoma-associated antigen D1 (MAGED1) OT6EOLFC MAGD1_HUMAN Affects Response To Substance [9]
Ferritin heavy chain (FTH1) OT6IFS0O FRIH_HUMAN Affects Response To Substance [9]
Protein-glutamine gamma-glutamyltransferase 2 (TGM2) OT6MFOWF TGM2_HUMAN Affects Response To Substance [9]
G-protein-signaling modulator 2 (GPSM2) OT6RPMRM GPSM2_HUMAN Affects Response To Substance [9]
Cytochrome b5 (CYB5A) OT6SN4RM CYB5_HUMAN Affects Response To Substance [9]
Ankycorbin (RAI14) OT6USGBK RAI14_HUMAN Affects Response To Substance [9]
Plasminogen activator inhibitor 2 (SERPINB2) OT72QLZB PAI2_HUMAN Affects Response To Substance [9]
Replication protein A 70 kDa DNA-binding subunit (RPA1) OT76POLP RFA1_HUMAN Affects Response To Substance [9]
Signal transducer CD24 (CD24) OT7CODJ4 CD24_HUMAN Affects Response To Substance [9]
Polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3) OT7M67WT GALT3_HUMAN Affects Response To Substance [9]
Fibroblast growth factor 2 (FGF2) OT7YUJ9F FGF2_HUMAN Affects Response To Substance [9]
Forkhead box protein D1 (FOXD1) OT80PRHS FOXD1_HUMAN Affects Response To Substance [9]
Cbp/p300-interacting transactivator 2 (CITED2) OT812TV7 CITE2_HUMAN Affects Response To Substance [9]
Raftlin (RFTN1) OT8875JE RFTN1_HUMAN Affects Response To Substance [9]
Mesoderm-specific transcript homolog protein (MEST) OT8Q4U8Y MEST_HUMAN Affects Response To Substance [9]
Four-jointed box protein 1 (FJX1) OT8SVTSS FJX1_HUMAN Affects Response To Substance [9]
Leptin receptor (LEPR) OT9H7G0C LEPR_HUMAN Affects Response To Substance [9]
Calmodulin-regulated spectrin-associated protein 2 (CAMSAP2) OT9KXWE7 CAMP2_HUMAN Affects Response To Substance [9]
Oxidoreductase HTATIP2 (HTATIP2) OT9MZ4QO HTAI2_HUMAN Affects Response To Substance [9]
Tissue factor pathway inhibitor (TFPI) OTA0FX16 TFPI1_HUMAN Affects Response To Substance [9]
High mobility group nucleosome-binding domain-containing protein 3 (HMGN3) OTA2TBWS HMGN3_HUMAN Affects Response To Substance [9]
Diphosphoinositol polyphosphate phosphohydrolase NUDT4B (NUDT4) OTA6ICI2 NUD4B_HUMAN Affects Response To Substance [9]
SEC14-like protein 1 (SEC14L1) OTA75FET S14L1_HUMAN Affects Response To Substance [9]
Autism susceptibility gene 2 protein (AUTS2) OTAEXHSC AUTS2_HUMAN Affects Response To Substance [9]
Grancalcin (GCA) OTAJ7ZHG GRAN_HUMAN Affects Response To Substance [9]
RNA polymerase II elongation factor ELL3 (ELL3) OTALC1YD ELL3_HUMAN Affects Response To Substance [9]
Receptor-type tyrosine-protein phosphatase kappa (PTPRK) OTAP5AT3 PTPRK_HUMAN Affects Response To Substance [9]
snRNA-activating protein complex subunit 1 (SNAPC1) OTAPN1NI SNPC1_HUMAN Affects Response To Substance [9]
Cyclin-dependent kinase inhibitor 1C (CDKN1C) OTASTJ3Q CDN1C_HUMAN Affects Response To Substance [9]
Stearoyl-CoA desaturase (SCD) OTB1073G SCD_HUMAN Affects Response To Substance [9]
Desmoplakin (DSP) OTB2MOP8 DESP_HUMAN Affects Response To Substance [9]
Protein lin-7 homolog C (LIN7C) OTB3015O LIN7C_HUMAN Affects Response To Substance [9]
Heterogeneous nuclear ribonucleoprotein D-like (HNRNPDL) OTB3BFCV HNRDL_HUMAN Affects Response To Substance [9]
High mobility group protein HMGI-C (HMGA2) OTBMBHHL HMGA2_HUMAN Affects Response To Substance [9]
Microtubule-associated tumor suppressor 1 (MTUS1) OTBPALMU MTUS1_HUMAN Affects Response To Substance [9]
Cilium assembly protein DZIP1 (DZIP1) OTBVPO66 DZIP1_HUMAN Affects Response To Substance [9]
Thiamin pyrophosphokinase 1 (TPK1) OTCHPUD0 TPK1_HUMAN Affects Response To Substance [9]
Cytoskeleton-associated protein 2 (CKAP2) OTCLTC0J CKAP2_HUMAN Affects Response To Substance [9]
Hydroxymethylglutaryl-CoA synthase, cytoplasmic (HMGCS1) OTCO26FV HMCS1_HUMAN Affects Response To Substance [9]
Cytochrome c oxidase copper chaperone (COX17) OTCP4LH2 COX17_HUMAN Affects Response To Substance [9]
Tetraspanin-13 (TSPAN13) OTCS9BZY TSN13_HUMAN Affects Response To Substance [9]
S-phase kinase-associated protein 2 (SKP2) OTD5B41X SKP2_HUMAN Affects Response To Substance [9]
Tropomyosin alpha-1 chain (TPM1) OTD73X6R TPM1_HUMAN Affects Response To Substance [9]
Keratin, type I cytoskeletal 19 (KRT19) OTDGDQ75 K1C19_HUMAN Affects Response To Substance [9]
Integrin alpha-1 (ITGA1) OTDITIST ITA1_HUMAN Increases Response To Substance [10]
AP-5 complex subunit mu-1 (AP5M1) OTDLWEBL AP5M1_HUMAN Affects Response To Substance [9]
Protein eva-1 homolog B (EVA1B) OTDNAKQD EVA1B_HUMAN Affects Response To Substance [9]
Gamma-adducin (ADD3) OTDRSHAZ ADDG_HUMAN Affects Response To Substance [9]
Dickkopf-related protein 3 (DKK3) OTDU94EY DKK3_HUMAN Affects Response To Substance [9]
Ras-related protein Rab-7L1 (RAB29) OTDZT6LP RAB7L_HUMAN Affects Response To Substance [9]
Short transient receptor potential channel 1 (TRPC1) OTEEAGLH TRPC1_HUMAN Affects Response To Substance [9]
H(+)/Cl(-) exchange transporter 3 (CLCN3) OTEEXNMU CLCN3_HUMAN Affects Response To Substance [9]
Secernin-1 (SCRN1) OTELM5C2 SCRN1_HUMAN Affects Response To Substance [9]
NGFI-A-binding protein 1 (NAB1) OTEWHIZR NAB1_HUMAN Affects Response To Substance [9]
Serglycin (SRGN) OTFAVSX0 SRGN_HUMAN Affects Response To Substance [9]
Solute carrier family 35 member G2 (SLC35G2) OTFBVS0P S35G2_HUMAN Affects Response To Substance [9]
Cadherin-1 (CDH1) OTFJMXPM CADH1_HUMAN Affects Response To Substance [9]
Multiple C2 and transmembrane domain-containing protein 2 (MCTP2) OTFMZ8I2 MCTP2_HUMAN Affects Response To Substance [9]
Caveolae-associated protein 1 (CAVIN1) OTFO915U CAVN1_HUMAN Affects Response To Substance [9]
Laminin subunit alpha-2 (LAMA2) OTFROQWE LAMA2_HUMAN Increases Response To Substance [10]
Centriolar satellite-associated tubulin polyglutamylase complex regulator 1 (CSTPP1) OTFSO3XV CSTP1_HUMAN Affects Response To Substance [9]
Baculoviral IAP repeat-containing protein 2 (BIRC2) OTFXFREP BIRC2_HUMAN Affects Response To Substance [9]
Myelin basic protein (MBP) OTFZCEDB MBP_HUMAN Affects Response To Substance [9]
Transmembrane protein 80 (TMEM80) OTG9D4KX TMM80_HUMAN Affects Response To Substance [9]
Squalene synthase (FDFT1) OTGDISIT FDFT_HUMAN Affects Response To Substance [9]
High mobility group protein B2 (HMGB2) OTGEGAOK HMGB2_HUMAN Affects Response To Substance [9]
Cytotoxic granule associated RNA binding protein TIA1 (TIA1) OTGPN3P8 TIA1_HUMAN Affects Response To Substance [9]
Stanniocalcin-1 (STC1) OTGVVXYF STC1_HUMAN Affects Response To Substance [9]
Sigma intracellular receptor 2 (TMEM97) OTH76ZWK SGMR2_HUMAN Affects Response To Substance [9]
Epithelial cell adhesion molecule (EPCAM) OTHBZK5X EPCAM_HUMAN Affects Response To Substance [9]
Delta-aminolevulinic acid dehydratase (ALAD) OTHM9GSH HEM2_HUMAN Affects Response To Substance [9]
DNA damage-inducible transcript 4 protein (DDIT4) OTHY8SY4 DDIT4_HUMAN Affects Response To Substance [9]
Interstitial collagenase (MMP1) OTI4I2V1 MMP1_HUMAN Affects Response To Substance [9]
Solute carrier family 38 member 6 (SLC38A6) OTIC8SHQ S38A6_HUMAN Affects Response To Substance [9]
Histone-lysine N-methyltransferase EZH2 (EZH2) OTIEHTKW EZH2_HUMAN Affects Response To Substance [9]
G2/mitotic-specific cyclin-B2 (CCNB2) OTIEXTDK CCNB2_HUMAN Affects Response To Substance [9]
Laminin subunit gamma-1 (LAMC1) OTIG527N LAMC1_HUMAN Affects Response To Substance [9]
Cyclin-G2 (CCNG2) OTII38K2 CCNG2_HUMAN Affects Response To Substance [9]
Beta/gamma crystallin domain-containing protein 1 (CRYBG1) OTIPDI15 CRBG1_HUMAN Affects Response To Substance [9]
Ras-related protein Rab-13 (RAB13) OTIQ484I RAB13_HUMAN Affects Response To Substance [9]
Insulin-like growth factor-binding protein 3 (IGFBP3) OTIX63TX IBP3_HUMAN Affects Response To Substance [9]
Ankyrin repeat domain-containing protein 10 (ANKRD10) OTIZ2VK8 ANR10_HUMAN Affects Response To Substance [9]
Histone deacetylase complex subunit SAP18 (SAP18) OTJAZWOL SAP18_HUMAN Affects Response To Substance [9]
E3 ubiquitin-protein ligase FANCL (FANCL) OTJC7QPQ FANCL_HUMAN Affects Response To Substance [9]
Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial (HADH) OTJDOL20 HCDH_HUMAN Affects Response To Substance [9]
FERM domain-containing protein 4A (FRMD4A) OTJDTIK2 FRM4A_HUMAN Affects Response To Substance [9]
Cyclin-F (CCNF) OTJFVU43 CCNF_HUMAN Affects Response To Substance [9]
Osteopontin (SPP1) OTJGC23Y OSTP_HUMAN Affects Response To Substance [9]
Jupiter microtubule associated homolog 2 (JPT2) OTJGPA4T JUPI2_HUMAN Affects Response To Substance [9]
TBC1 domain family member 4 (TBC1D4) OTK66C40 TBCD4_HUMAN Affects Response To Substance [9]
Tumor necrosis factor receptor superfamily member 6B (TNFRSF6B) OTKAN9G7 TNF6B_HUMAN Affects Response To Substance [9]
Myelin protein zero-like protein 2 (MPZL2) OTKFNDUI MPZL2_HUMAN Affects Response To Substance [9]
Transmembrane channel-like protein 6 (TMC6) OTKH50J4 TMC6_HUMAN Affects Response To Substance [9]
Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2) OTKOZRZP PLOD2_HUMAN Affects Response To Substance [9]
Methylsterol monooxygenase 1 (MSMO1) OTKV62RZ MSMO1_HUMAN Affects Response To Substance [9]
Enolase-phosphatase E1 (ENOPH1) OTKXMWNN ENOPH_HUMAN Affects Response To Substance [9]
Calcium-binding tyrosine phosphorylation-regulated protein (CABYR) OTKYMT99 CABYR_HUMAN Affects Response To Substance [9]
Glycylpeptide N-tetradecanoyltransferase 2 (NMT2) OTLNA39Z NMT2_HUMAN Affects Response To Substance [9]
Hemicentin-1 (HMCN1) OTLZAS0P HMCN1_HUMAN Increases Response To Substance [10]
Ribosome biogenesis protein BOP1 (BOP1) OTMZMQDO BOP1_HUMAN Affects Response To Substance [9]
Eukaryotic peptide chain release factor GTP-binding subunit ERF3B (GSPT2) OTN0K7F3 ERF3B_HUMAN Affects Response To Substance [9]
Four and a half LIM domains protein 1 (FHL1) OTN535SU FHL1_HUMAN Affects Response To Substance [9]
MAP kinase-interacting serine/threonine-protein kinase 2 (MKNK2) OTNA9G8V MKNK2_HUMAN Affects Response To Substance [9]
Epithelial splicing regulatory protein 1 (ESRP1) OTNCS4SL ESRP1_HUMAN Affects Response To Substance [9]
Radixin (RDX) OTNSYUN6 RADI_HUMAN Affects Response To Substance [9]
Calcium-activated potassium channel subunit alpha-1 (KCNMA1) OTNYXOZO KCMA1_HUMAN Affects Response To Substance [9]
Paraneoplastic antigen-like protein 8A (PNMA8A) OTO3F7B0 PNM8A_HUMAN Affects Response To Substance [9]
Polypeptide N-acetylgalactosaminyltransferase 1 (GALNT1) OTO3RO36 GALT1_HUMAN Affects Response To Substance [9]
Histone deacetylase 9 (HDAC9) OTO8O0LF HDAC9_HUMAN Affects Response To Substance [9]
Histone-lysine N-methyltransferase KMT5B (KMT5B) OTOH7G8Q KMT5B_HUMAN Affects Response To Substance [9]
BH3-interacting domain death agonist (BID) OTOSHSHU BID_HUMAN Affects Response To Substance [9]
GTP cyclohydrolase 1 (GCH1) OTOZ6NSL GCH1_HUMAN Affects Response To Substance [9]
Unconventional myosin-Id (MYO1D) OTP2RGPN MYO1D_HUMAN Affects Response To Substance [9]
Rho GTPase-activating protein 7 (DLC1) OTP8LMCR RHG07_HUMAN Affects Response To Substance [9]
Ras-related protein Rab-20 (RAB20) OTP9OOVS RAB20_HUMAN Affects Response To Substance [9]
Dual specificity protein phosphatase 3 (DUSP3) OTPJX9B4 DUS3_HUMAN Affects Response To Substance [9]
DNA dC->dU-editing enzyme APOBEC-3C (APOBEC3C) OTPL0AI1 ABC3C_HUMAN Affects Response To Substance [9]
Pentraxin-related protein PTX3 (PTX3) OTPXHRKU PTX3_HUMAN Affects Response To Substance [9]
Dermatan-sulfate epimerase (DSE) OTQ108VJ DSE_HUMAN Affects Response To Substance [9]
Centromere protein U (CENPU) OTQ4TZRS CENPU_HUMAN Affects Response To Substance [9]
Eukaryotic translation initiation factor 5A-1 (EIF5A) OTQ8DJX5 IF5A1_HUMAN Affects Response To Substance [9]
Sortilin-related receptor (SORL1) OTQ8FFNS SORL_HUMAN Affects Response To Substance [9]
Collagen alpha-2(VI) chain (COL6A2) OTQC6PPO CO6A2_HUMAN Affects Response To Substance [9]
Ran-specific GTPase-activating protein (RANBP1) OTQE226K RANG_HUMAN Affects Response To Substance [9]
MAPK/MAK/MRK overlapping kinase (MOK) OTQK7M9V MOK_HUMAN Affects Response To Substance [9]
3-oxo-5-alpha-steroid 4-dehydrogenase 1 (SRD5A1) OTQRET2B S5A1_HUMAN Affects Response To Substance [9]
High mobility group protein HMG-I/HMG-Y (HMGA1) OTQUSHPX HMGA1_HUMAN Affects Response To Substance [9]
Keratin, type I cytoskeletal 23 (KRT23) OTQW6UAG K1C23_HUMAN Increases Response To Substance [10]
Transforming growth factor-beta-induced protein ig-h3 (TGFBI) OTR443C5 BGH3_HUMAN Decreases Response To Substance [10]
Large ribosomal subunit protein mL63 (MRPL57) OTRB659E RT63_HUMAN Affects Response To Substance [9]
Actin, gamma-enteric smooth muscle (ACTG2) OTRDWUO0 ACTH_HUMAN Affects Response To Substance [9]
Acidic leucine-rich nuclear phosphoprotein 32 family member A (ANP32A) OTRHPFO2 AN32A_HUMAN Affects Response To Substance [9]
LIM domain kinase 2 (LIMK2) OTRJD7VZ LIMK2_HUMAN Affects Response To Substance [9]
Calcium/calmodulin-dependent protein kinase type 1 (CAMK1) OTRN55RE KCC1A_HUMAN Affects Response To Substance [9]
Receptor tyrosine-protein kinase erbB-3 (ERBB3) OTRSST0A ERBB3_HUMAN Affects Response To Substance [9]
Lysyl oxidase homolog 2 (LOXL2) OTRT46B5 LOXL2_HUMAN Affects Response To Substance [9]
Arginine and glutamate-rich protein 1 (ARGLU1) OTRVRZ4Z ARGL1_HUMAN Affects Response To Substance [9]
Dr1-associated corepressor (DRAP1) OTRWLF6D NC2A_HUMAN Affects Response To Substance [9]
Latent-transforming growth factor beta-binding protein 2 (LTBP2) OTS88GSD LTBP2_HUMAN Affects Response To Substance [9]
Heat shock-related 70 kDa protein 2 (HSPA2) OTSDET7B HSP72_HUMAN Affects Response To Substance [9]
Inhibin beta A chain (INHBA) OTSP64PQ INHBA_HUMAN Affects Response To Substance [9]
Lumican (LUM) OTSRC874 LUM_HUMAN Decreases Response To Substance [10]
GTP-binding protein SAR1a (SAR1A) OTSSRVGV SAR1A_HUMAN Affects Response To Substance [9]
Plasminogen activator inhibitor 1 (SERPINE1) OTT0MPQ3 PAI1_HUMAN Affects Response To Substance [9]
Collagen alpha-1(III) chain (COL3A1) OTT1EMLM CO3A1_HUMAN Decreases Response To Substance [10]
DNA-binding protein SATB1 (SATB1) OTT7SUVW SATB1_HUMAN Affects Response To Substance [9]
Gap junction alpha-1 protein (GJA1) OTT94MKL CXA1_HUMAN Affects Response To Substance [9]
KH domain-containing RNA-binding protein QKI (QKI) OTTAUGLB QKI_HUMAN Affects Response To Substance [9]
Cullin-4A (CUL4A) OTTBV70J CUL4A_HUMAN Affects Response To Substance [9]
Homeobox protein Hox-B2 (HOXB2) OTTD6HMV HXB2_HUMAN Affects Response To Substance [9]
Collagen alpha-1(XV) chain (COL15A1) OTTFKK18 COFA1_HUMAN Decreases Response To Substance [10]
A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1) OTTLJH8W ATS1_HUMAN Affects Response To Substance [9]
Nuclear receptor-interacting protein 3 (NRIP3) OTU15GMK NRIP3_HUMAN Affects Response To Substance [9]
Granulocyte-macrophage colony-stimulating factor receptor subunit alpha (CSF2RA) OTUOO2XS CSF2R_HUMAN Affects Response To Substance [9]
La-related protein 6 (LARP6) OTUQ9QS9 LARP6_HUMAN Affects Response To Substance [9]
General transcription factor II-I (GTF2I) OTUYL1TQ GTF2I_HUMAN Affects Response To Substance [9]
Protein aurora borealis (BORA) OTV2ZPKP BORA_HUMAN Affects Response To Substance [9]
FYVE, RhoGEF and PH domain-containing protein 1 (FGD1) OTV3T64P FGD1_HUMAN Affects Response To Substance [9]
Matrilin-2 (MATN2) OTVDR68G MATN2_HUMAN Decreases Response To Substance [10]
Microtubule-actin cross-linking factor 1, isoforms 1/2/3/4/5 (MACF1) OTVIHD77 MACF1_HUMAN Affects Response To Substance [9]
Serine protease FAM111A (FAM111A) OTVLARLG F111A_HUMAN Affects Response To Substance [9]
Transcription factor 7-like 2 (TCF7L2) OTVWPZ8B TF7L2_HUMAN Affects Response To Substance [9]
Interleukin-1 receptor accessory protein-like 1 (IL1RAPL1) OTW3T4B2 IRPL1_HUMAN Affects Response To Substance [9]
Transcription factor E2-alpha (TCF3) OTW6FR32 TFE2_HUMAN Affects Response To Substance [9]
Tissue alpha-L-fucosidase (FUCA1) OTW71IK4 FUCO_HUMAN Affects Response To Substance [9]
Fanconi anemia group I protein (FANCI) OTW8E3SC FANCI_HUMAN Affects Response To Substance [9]
U2 small nuclear ribonucleoprotein A' (SNRPA1) OTWJZFAP RU2A_HUMAN Affects Response To Substance [9]
Decorin (DCN) OTWLJL7K PGS2_HUMAN Decreases Response To Substance [10]
Periostin (POSTN) OTWP62UA POSTN_HUMAN Decreases Response To Substance [10]
Methyl-CpG-binding domain protein 4 (MBD4) OTWR9YXE MBD4_HUMAN Affects Response To Substance [9]
Glypican-3 (GPC3) OTWS8WSW GPC3_HUMAN Increases Response To Substance [10]
GDP-mannose 4,6 dehydratase (GMDS) OTWV79YD GMDS_HUMAN Affects Response To Substance [9]
ORC ubiquitin ligase 1 (OBI1) OTX62ZHW OBI1_HUMAN Affects Response To Substance [9]
Caspase-6 (CASP6) OTXLD3EC CASP6_HUMAN Affects Response To Substance [9]
Condensin complex subunit 2 (NCAPH) OTXOS97C CND2_HUMAN Affects Response To Substance [9]
Collagen alpha-2(I) chain (COL1A2) OTY7G382 CO1A2_HUMAN Increases Response To Substance [10]
Collagen alpha-1(VI) chain (COL6A1) OTYKSCOB CO6A1_HUMAN Affects Response To Substance [9]
Protein FAN (NSMAF) OTYNVZ23 FAN_HUMAN Affects Response To Substance [9]
Protein Niban 1 (NIBAN1) OTYOLI12 NIBA1_HUMAN Affects Response To Substance [9]
Nucleolar complex protein 3 homolog (NOC3L) OTYOR3PV NOC3L_HUMAN Affects Response To Substance [9]
Procathepsin L (CTSL) OTYTUW29 CATL1_HUMAN Affects Response To Substance [9]
Acetyl-CoA acetyltransferase, cytosolic (ACAT2) OTZ092ZJ THIC_HUMAN Affects Response To Substance [9]
Thiosulfate sulfurtransferase (TST) OTZ4F5LK THTR_HUMAN Affects Response To Substance [9]
Tissue factor pathway inhibitor 2 (TFPI2) OTZCRWOR TFPI2_HUMAN Affects Response To Substance [9]
Insulin-induced gene 1 protein (INSIG1) OTZF5X1D INSI1_HUMAN Affects Response To Substance [9]
Suppressor of tumorigenicity 7 protein (ST7) OTZG8RC6 ST7_HUMAN Affects Response To Substance [9]
Fermitin family homolog 2 (FERMT2) OTZNPWWX FERM2_HUMAN Affects Response To Substance [9]
------------------------------------------------------------------------------------
⏷ Show the Full List of 246 DOT(s)
Indication(s) of MK-2206
Disease Entry ICD 11 Status REF
Rectal adenocarcinoma 2B92 Phase 2 [6]
Nasopharyngeal carcinoma 2B6B Investigative [7]
MK-2206 Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
RAC-gamma serine/threonine-protein kinase (AKT3) TTAZ05C AKT3_HUMAN Modulator [30]
E2 ubiquitin-conjugating enzyme T (UBE2T) TT0A1R8 UBE2T_HUMAN Inhibitor [7]
------------------------------------------------------------------------------------
MK-2206 Interacts with 20 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Epidermal growth factor receptor (EGFR) OTAPLO1S EGFR_HUMAN Increases Expression [31]
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Decreases Secretion [29]
Receptor tyrosine-protein kinase erbB-2 (ERBB2) OTOAUNCK ERBB2_HUMAN Increases Expression [31]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Decreases Secretion [29]
Endothelin-1 (EDN1) OTZCACEG EDN1_HUMAN Decreases Expression [29]
Tissue factor (F3) OT3MSU3B TF_HUMAN Increases Expression [32]
Vascular endothelial growth factor receptor 1 (FLT1) OTT0OGYS VGFR1_HUMAN Decreases Expression [29]
Interleukin-10 (IL10) OTIRFRXC IL10_HUMAN Increases Secretion [29]
Endothelin receptor type B (EDNRB) OTLLZV3P EDNRB_HUMAN Increases Expression [29]
Tumor necrosis factor receptor superfamily member 6 (FAS) OTP9XG86 TNR6_HUMAN Affects Response To Substance [33]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Phosphorylation [34]
T-lymphocyte activation antigen CD80 (CD80) OTJBLUQE CD80_HUMAN Decreases Expression [29]
T-lymphocyte activation antigen CD86 (CD86) OTJCSBPC CD86_HUMAN Decreases Expression [29]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Cleavage [34]
CCAAT/enhancer-binding protein alpha (CEBPA) OTOM9OE4 CEBPA_HUMAN Decreases Expression [29]
Actin, aortic smooth muscle (ACTA2) OTEDLG8E ACTA_HUMAN Decreases Expression [35]
Small ribosomal subunit protein eS6 (RPS6) OTT4D1LN RS6_HUMAN Decreases Phosphorylation [34]
Interferon regulatory factor 8 (IRF8) OT8YSNI4 IRF8_HUMAN Decreases Expression [29]
Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) OTHBQVD5 4EBP1_HUMAN Decreases Phosphorylation [34]
Proline-rich AKT1 substrate 1 (AKT1S1) OT4JHN4Y AKTS1_HUMAN Decreases Phosphorylation [36]
------------------------------------------------------------------------------------
⏷ Show the Full List of 20 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Breast and ovarian cancer syndrome DCAL1IK UWB1289+BRCA1 Investigative [1]
Carcinoma DCDXGKV EFM192B Investigative [1]
Colon carcinoma DCLQH29 RKO Investigative [1]
Adenocarcinoma DC5D6RM CAOV3 Investigative [37]
Adenocarcinoma DCNAVCI A427 Investigative [37]
Adenocarcinoma DC0XMY0 NCIH2122 Investigative [37]
Adenocarcinoma DCP2R03 COLO320DM Investigative [37]
Adenocarcinoma DCMKSFO DLD1 Investigative [37]
Adenocarcinoma DC594EO HCT116 Investigative [37]
Adenocarcinoma DC64U2C HT29 Investigative [37]
Adenocarcinoma DC1G82Y SW-620 Investigative [37]
Amelanotic melanoma DC6F4NY A2058 Investigative [37]
Germ cell tumour DC8OH29 PA1 Investigative [37]
Malignant melanoma DCKQZHI SKMEL30 Investigative [37]
Ovarian endometrioid adenocarcinoma DC44EG3 A2780 Investigative [37]
Ovarian serous cystadenocarcinoma DCOL852 SK-OV-3 Investigative [37]
------------------------------------------------------------------------------------
⏷ Show the Full List of 16 DrugCom(s)

References

1 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.
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 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: 7945).
7 UBE2T promotes nasopharyngeal carcinoma cell proliferation, invasion, and metastasis by activating the AKT/GSK3/-catenin pathway.Oncotarget. 2016 Mar 22;7(12):15161-72.
8 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.
9 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.
10 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.
11 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
12 Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
13 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.
14 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.
15 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.
16 Topotecan is a substrate for multidrug resistance associated protein 4. Curr Drug Metab. 2006 Jan;7(1):105-18.
17 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.
18 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.
19 Cancer cell adaptation to chemotherapy. BMC Cancer. 2005 Jul 18;5:78.
20 The effect of Topotecan on oxidative stress in MCF-7 human breast cancer cell line. Acta Biochim Pol. 2005;52(4):897-902.
21 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.
22 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.
23 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.
24 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.
25 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.
26 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.
27 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.
28 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.
29 Chemerin promotes the pathogenesis of preeclampsia by activating CMKLR1/p-Akt/CEBP axis and inducing M1 macrophage polarization. Cell Biol Toxicol. 2022 Aug;38(4):611-628. doi: 10.1007/s10565-021-09636-7. Epub 2021 Aug 16.
30 First-in-man clinical trial of the oral pan-AKT inhibitor MK-2206 in patients with advanced solid tumors.J Clin Oncol.2011 Dec 10;29(35):4688-95.
31 Platycodin D potentiates proliferation inhibition and apoptosis induction upon AKT inhibition via feedback blockade in non-small cell lung cancer cells. Sci Rep. 2016 Nov 29;6:37997. doi: 10.1038/srep37997.
32 Elucidating mechanisms of toxicity using phenotypic data from primary human cell systems--a chemical biology approach for thrombosis-related side effects. Int J Mol Sci. 2015 Jan 5;16(1):1008-29. doi: 10.3390/ijms16011008.
33 PI3K/AKT inhibitors aggravate death receptor-mediated hepatocyte apoptosis and liver injury. Toxicol Appl Pharmacol. 2019 Oct 15;381:114729. doi: 10.1016/j.taap.2019.114729. Epub 2019 Aug 22.
34 Harnessing the PI3K/Akt/mTOR pathway in T-cell acute lymphoblastic leukemia: eliminating activity by targeting at different levels. Oncotarget. 2012 Aug;3(8):811-23. doi: 10.18632/oncotarget.579.
35 -Mangostin alleviates liver fibrosis through Sirtuin 3-superoxide-high mobility group box 1 signaling axis. Toxicol Appl Pharmacol. 2019 Jan 15;363:142-153. doi: 10.1016/j.taap.2018.11.011. Epub 2018 Nov 29.
36 Akt activation by Ca(2+)/calmodulin-dependent protein kinase kinase 2 (CaMKK2) in ovarian cancer cells. J Biol Chem. 2017 Aug 25;292(34):14188-14204. doi: 10.1074/jbc.M117.778464. Epub 2017 Jun 20.
37 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.