Details of the Drug Combination

General Information of Drug Combination (ID: DC8LHHK)

Drug Combination Name

Topotecan Imatinib

Indication

Disease Entry	Status	REF
Melanoma	Investigative	[1]

Component Drugs

Topotecan DMP6G8T

Imatinib DM7RJXL

Small molecular drug

2D MOL

3D MOL

High-throughput Screening Result

Testing Cell Line: MALME-3M

Zero Interaction Potency (ZIP) Score: 4.18

Bliss Independence Score: 4.92

Loewe Additivity Score: 1.17

LHighest Single Agent (HSA) Score: 3.04

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

Indication(s) of Imatinib

Disease Entry	ICD 11	Status	REF
Acute lymphoblastic leukaemia	2A85	Approved	[6]
Blast phase chronic myelogenous leukemia, BCR-ABL1 positive	N.A.	Approved	[7]
Choroidal neovascularization	9B76	Approved	[7]
Chronic eosinophilic leukemia	N.A.	Approved	[7]
Chronic myelogenous leukaemia	2A20.0	Approved	[8]
Chronic myeloid leukaemia	2A20	Approved	[9]
Dermatofibrosarcoma protuberans	N.A.	Approved	[7]
Gastrointestinal stromal tumour	2B5B	Approved	[7]
Leukemia	N.A.	Approved	[7]
Malignant peripheral nerve sheath tumor	N.A.	Approved	[7]
Myeloproliferative neoplasm	2A20	Approved	[7]
Pulmonary hypertension	BB01	Approved	[7]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 3	[10]
Intestinal cancer	2C0Z	Phase 3	[8]
Lung cancer	2C25.0	Phase 2	[8]
Idiopathic hypereosinophilic syndrome	N.A.	Investigative	[7]
Middle East Respiratory Syndrome (MERS)	1D64	Investigative	[11]
Scleroderma	4A42	Investigative	[7]
Severe acute respiratory syndrome (SARS)	1D65	Investigative	[11]
Systemic mastocytosis	2A21.0	Investigative	[12]

Imatinib Interacts with 5 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Mcl-1 messenger RNA (MCL-1 mRNA)	TTN6ORK	MCL1_HUMAN	.	[12]
Fusion protein Bcr-Abl (Bcr-Abl)	TTS7G69	BCR_HUMAN-ABL1_HUMAN	Inhibitor	[37]
Platelet-derived growth factor receptor (PDGFR)	TTI2WET	NOUNIPROTAC	Inhibitor	[37]
Tyrosine-protein kinase Kit (KIT)	TTX41N9	KIT_HUMAN	Inhibitor	[37]
HUMAN fusion protein Bcr-Abl (Bcr-Abl)	TTE63HY	BCR_HUMAN/ABL1_HUMAN	Inhibitor	[11]
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Imatinib Interacts with 6 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[38]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[39]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[40]
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[41]
Organic anion transporting polypeptide 1A2 (SLCO1A2)	DTE2B1D	SO1A2_HUMAN	Substrate	[42]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[40]
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⏷ Show the Full List of 6 DTP(s)

Imatinib Interacts with 8 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[43]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[44]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[45]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[46]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[47]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[48]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[49]
Prostaglandin G/H synthase 1 (COX-1)	DE073H6	PGH1_HUMAN	Metabolism	[45]
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⏷ Show the Full List of 8 DME(s)

Imatinib Interacts with 95 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Decreases Methylation	[50]
Cytochrome P450 3A5 (CYP3A5)	OTSXFBXB	CP3A5_HUMAN	Decreases Methylation	[50]
Cytochrome P450 3A7 (CYP3A7)	OTTCDHHM	CP3A7_HUMAN	Decreases Methylation	[50]
Cytochrome P450 2C8 (CYP2C8)	OTHCWT42	CP2C8_HUMAN	Decreases Methylation	[50]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2)	OTW8V2V1	ABCG2_HUMAN	Increases Expression	[51]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Expression	[51]
Aldehyde dehydrogenase, mitochondrial (ALDH2)	OTKJ9I3N	ALDH2_HUMAN	Decreases Expression	[52]
Eukaryotic translation initiation factor 4E (EIF4E)	OTDAWNLA	IF4E_HUMAN	Decreases Expression	[52]
Fructose-bisphosphate aldolase C (ALDOC)	OTEC13I5	ALDOC_HUMAN	Decreases Expression	[52]
Pyruvate dehydrogenase E1 component subunit beta, mitochondrial (PDHB)	OT2NHE5E	ODPB_HUMAN	Decreases Expression	[52]
Cyclin-dependent kinase 4 (CDK4)	OT7EP05T	CDK4_HUMAN	Decreases Expression	[52]
Cyclin-A2 (CCNA2)	OTPHHYZJ	CCNA2_HUMAN	Decreases Expression	[52]
Ribosomal protein S6 kinase beta-1 (RPS6KB1)	OTAELNGX	KS6B1_HUMAN	Decreases Expression	[52]
Eukaryotic translation initiation factor 4B (EIF4B)	OTE8TXA8	IF4B_HUMAN	Decreases Expression	[52]
Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1)	OT5BZ1J9	P85A_HUMAN	Decreases Expression	[52]
G1/S-specific cyclin-D3 (CCND3)	OTNKPQ22	CCND3_HUMAN	Decreases Expression	[52]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Decreases Expression	[52]
Hexokinase-4 (GCK)	OTR3Q0NN	HXK4_HUMAN	Decreases Expression	[52]
Serine/threonine-protein kinase mTOR (MTOR)	OTHH8KU7	MTOR_HUMAN	Decreases Expression	[52]
Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform (PPP2CA)	OT83PT85	PP2AA_HUMAN	Increases Expression	[52]
Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1)	OTHBQVD5	4EBP1_HUMAN	Decreases Expression	[52]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[53]
Prostaglandin G/H synthase 2 (PTGS2)	OT75U9M4	PGH2_HUMAN	Decreases Expression	[54]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B)	OTA1CPBV	TR10B_HUMAN	Increases Expression	[55]
Autophagy-related protein 13 (ATG13)	OTYMHNEJ	ATG13_HUMAN	Increases Phosphorylation	[34]
Platelet-derived growth factor subunit B (PDGFB)	OTMFMFC3	PDGFB_HUMAN	Decreases Expression	[56]
Interferon gamma (IFNG)	OTXG9JM7	IFNG_HUMAN	Increases Expression	[57]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Increases Secretion	[58]
Keratin, type I cytoskeletal 14 (KRT14)	OTUVZ1DW	K1C14_HUMAN	Increases Expression	[59]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Expression	[60]
Heat shock protein beta-1 (HSPB1)	OTHFZ8ED	HSPB1_HUMAN	Increases Expression	[55]
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Decreases Activity	[61]
Intercellular adhesion molecule 1 (ICAM1)	OTTOIX77	ICAM1_HUMAN	Increases Expression	[55]
Tyrosine-protein kinase Lck (LCK)	OT883FG9	LCK_HUMAN	Decreases Phosphorylation	[62]
Cyclin-dependent kinase 1 (CDK1)	OTW1SC2N	CDK1_HUMAN	Decreases Expression	[57]
Cathepsin B (CTSB)	OTP9G5QB	CATB_HUMAN	Increases Expression	[34]
Proto-oncogene tyrosine-protein kinase receptor Ret (RET)	OTLU040A	RET_HUMAN	Decreases Phosphorylation	[63]
ATP-dependent 6-phosphofructokinase, muscle type (PFKM)	OT1QY9JM	PFKAM_HUMAN	Decreases Expression	[64]
Platelet-derived growth factor receptor beta (PDGFRB)	OTYSNK9Q	PGFRB_HUMAN	Decreases Expression	[56]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[65]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[55]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[66]
Solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1)	OTA675TJ	GTR1_HUMAN	Decreases Expression	[60]
Breakpoint cluster region protein (BCR)	OTCN76C1	BCR_HUMAN	Decreases Activity	[36]
Lysosome-associated membrane glycoprotein 1 (LAMP1)	OTYE92QY	LAMP1_HUMAN	Increases Expression	[34]
Ornithine decarboxylase (ODC1)	OTNDAGRR	DCOR_HUMAN	Increases Expression	[55]
Keratin, type II cytoskeletal 5 (KRT5)	OTVGI9HT	K2C5_HUMAN	Increases Expression	[59]
Tissue factor (F3)	OT3MSU3B	TF_HUMAN	Increases Expression	[67]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Expression	[68]
Platelet-derived growth factor receptor alpha (PDGFRA)	OTDJXUCN	PGFRA_HUMAN	Decreases Expression	[56]
CCAAT/enhancer-binding protein beta (CEBPB)	OTM9MQIA	CEBPB_HUMAN	Increases Expression	[55]
Histidine decarboxylase (HDC)	OT4WA5YQ	DCHS_HUMAN	Decreases Expression	[69]
Transcription factor EB (TFEB)	OTJUJJQY	TFEB_HUMAN	Affects Localization	[34]
Fibroblast growth factor receptor 3 (FGFR3)	OTSAXDIL	FGFR3_HUMAN	Decreases Expression	[70]
Insulin-like growth factor-binding protein 4 (IGFBP4)	OT2HZRBD	IBP4_HUMAN	Increases Expression	[55]
Alanine aminotransferase 1 (GPT)	OTOXOA0Q	ALAT1_HUMAN	Increases Secretion	[71]
Interleukin-4 receptor subunit alpha (IL4R)	OTTXOTCW	IL4RA_HUMAN	Increases Expression	[55]
Cyclin-dependent kinase 2 (CDK2)	OTB5DYYZ	CDK2_HUMAN	Decreases Expression	[57]
NF-kappa-B inhibitor alpha (NFKBIA)	OTFT924M	IKBA_HUMAN	Increases Phosphorylation	[55]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[62]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[62]
Caspase-1 (CASP1)	OTZ3YQFU	CASP1_HUMAN	Increases Cleavage	[58]
Catenin beta-1 (CTNNB1)	OTZ932A3	CTNB1_HUMAN	Decreases Expression	[72]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[73]
Crk-like protein (CRKL)	OTOYSD1R	CRKL_HUMAN	Decreases Phosphorylation	[74]
Glycogen synthase kinase-3 beta (GSK3B)	OTL3L14B	GSK3B_HUMAN	Increases Phosphorylation	[34]
Hexokinase-2 (HK2)	OTC0GCQO	HXK2_HUMAN	Decreases Expression	[64]
Small ribosomal subunit protein eS6 (RPS6)	OTT4D1LN	RS6_HUMAN	Decreases Phosphorylation	[34]
Heat shock factor protein 1 (HSF1)	OTYNJ4KP	HSF1_HUMAN	Increases Expression	[55]
Transcription factor p65 (RELA)	OTUJP9CN	TF65_HUMAN	Decreases Expression	[72]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[66]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Expression	[75]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1)	OT2YYI1A	MCL1_HUMAN	Decreases Expression	[65]
Forkhead box protein M1 (FOXM1)	OT5887KR	FOXM1_HUMAN	Decreases Expression	[72]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Decreases Activity	[76]
Sequestosome-1 (SQSTM1)	OTGY5D5J	SQSTM_HUMAN	Increases Expression	[34]
Beclin-1 (BECN1)	OT4X293M	BECN1_HUMAN	Increases Expression	[34]
Nuclear receptor subfamily 0 group B member 2 (NR0B2)	OT7UVICX	NR0B2_HUMAN	Increases Expression	[77]
NGFI-A-binding protein 2 (NAB2)	OTG4BDF3	NAB2_HUMAN	Increases Expression	[55]
Nuclear factor erythroid 2-related factor 2 (NFE2L2)	OT0HENJ5	NF2L2_HUMAN	Decreases Expression	[78]
Cytochrome P450 1B1 (CYP1B1)	OTYXFLSD	CP1B1_HUMAN	Decreases Activity	[61]
TRAF family member-associated NF-kappa-B activator (TANK)	OTZSGFIK	TANK_HUMAN	Increases Expression	[55]
NACHT, LRR and PYD domains-containing protein 3 (NLRP3)	OTZM6MHU	NLRP3_HUMAN	Increases Expression	[58]
Bile acid receptor (NR1H4)	OTWZLPTB	NR1H4_HUMAN	Increases Activity	[77]
Docking protein 1 (DOK1)	OTGVRLW6	DOK1_HUMAN	Decreases Phosphorylation	[79]
Microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B)	OTUYHB84	MLP3B_HUMAN	Increases Expression	[34]
Transcription factor SOX-17 (SOX17)	OT9H4WWE	SOX17_HUMAN	Decreases Localization	[80]
V-type proton ATPase subunit H (ATP6V1H)	OTX17GQ9	VATH_HUMAN	Increases Expression	[34]
Tyrosine-protein kinase ABL1 (ABL1)	OT09YVXH	ABL1_HUMAN	Increases Response To Substance	[81]
LYR motif-containing protein 9 (LYRM9)	OT1MILTK	LYRM9_HUMAN	Affects Response To Substance	[82]
Leptin (LEP)	OT5Q7ODW	LEP_HUMAN	Increases ADR	[83]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Response To Substance	[84]
Bcl-2-like protein 11 (BCL2L11)	OTNQQWFJ	B2L11_HUMAN	Increases Response To Substance	[85]
Tyrosine-protein kinase Lyn (LYN)	OTP686K2	LYN_HUMAN	Decreases Response To Substance	[74]
Serine/threonine-protein kinase PLK1 (PLK1)	OTRZX45T	PLK1_HUMAN	Increases Response To Substance	[65]
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⏷ Show the Full List of 95 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Carcinoma	DC10XIY	MCF7	Investigative	[86]
Adult T acute lymphoblastic leukemia	DCIMDQQ	MOLT-4	Investigative	[1]
Amelanotic melanoma	DCMJTKE	MDA-MB-435	Investigative	[1]
Chronic myelogenous leukemia	DC17H1X	KBM-7	Investigative	[1]
Glioma	DCWM19T	SF-268	Investigative	[1]
High grade ovarian serous adenocarcinoma	DCQS371	OVCAR-5	Investigative	[1]
Minimally invasive lung adenocarcinoma	DC1XXZT	NCI-H322M	Investigative	[1]
Mixed endometrioid and clear cell carcinoma	DCGKHKI	IGROV1	Investigative	[1]
Ovarian serous cystadenocarcinoma	DCNKQ3K	SK-OV-3	Investigative	[1]
Pleural epithelioid mesothelioma	DC44Z5Y	NCI-H226	Investigative	[1]
Prostate carcinoma	DC0JQZK	PC-3	Investigative	[1]
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⏷ Show the Full List of 11 DrugCom(s)

References

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2	Topotecan FDA Label
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6	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
7	Imatinib FDA Label
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9	FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (ANDA) 078340.
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18	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.
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21	Topotecan is a substrate for multidrug resistance associated protein 4. Curr Drug Metab. 2006 Jan;7(1):105-18.
22	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.
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24	Cancer cell adaptation to chemotherapy. BMC Cancer. 2005 Jul 18;5:78.
25	The effect of Topotecan on oxidative stress in MCF-7 human breast cancer cell line. Acta Biochim Pol. 2005;52(4):897-902.
26	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.
27	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.
28	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.
29	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.
30	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.
31	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.
32	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.
33	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.
34	Imatinib disturbs lysosomal function and morphology and impairs the activity of mTORC1 in human hepatocyte cell lines. Food Chem Toxicol. 2022 Apr;162:112869. doi: 10.1016/j.fct.2022.112869. Epub 2022 Feb 16.
35	Insulin-like growth factor I receptor pathway inhibition by ADW742, alone or in combination with imatinib, doxorubicin, or vincristine, is a novel therapeutic approach in Ewing tumor. Clin Cancer Res. 2006 Jun 1;12(11 Pt 1):3532-40. doi: 10.1158/1078-0432.CCR-05-1778.
36	Sensitivity to imatinib therapy may be predicted by testing Wilms tumor gene expression and colony growth after a short in vitro incubation. Cancer. 2004 Sep 1;101(5):979-88. doi: 10.1002/cncr.20457.
37	A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22.
38	Association of genetic polymorphisms in the influx transporter SLCO1B3 and the efflux transporter ABCB1 with imatinib pharmacokinetics in patients with chronic myeloid leukemia. Ther Drug Monit. 2011 Apr;33(2):244-50.
39	Imatinib mesylate (STI571) is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump. Blood. 2004 Nov 1;104(9):2940-2.
40	Contribution of OATP1B1 and OATP1B3 to the disposition of sorafenib and sorafenib-glucuronide. Clin Cancer Res. 2013 Mar 15;19(6):1458-66.
41	Pharmacologic markers and predictors of responses to imatinib therapy in patients with chronic myeloid leukemia. Leuk Lymphoma. 2008 Apr;49(4):639-42.
42	Environmental and genetic factors affecting transport of imatinib by OATP1A2. Clin Pharmacol Ther. 2011 Jun;89(6):816-20.
43	Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
44	The effect of apigenin on pharmacokinetics of imatinib and its metabolite N-desmethyl imatinib in rats. Biomed Res Int. 2013;2013:789184.
45	Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
46	Clinical pharmacokinetics of imatinib. Clin Pharmacokinet. 2005;44(9):879-94.
47	Drug Interactions Flockhart Table
48	Role of cytochrome P450 2C8 in drug metabolism and interactions. Pharmacol Rev. 2016 Jan;68(1):168-241.
49	Drug-drug interactions with imatinib: an observational study. Medicine (Baltimore). 2016 Oct;95(40):e5076.
50	Participation of CYP2C8 and CYP3A4 in the N-demethylation of imatinib in human hepatic microsomes. Br J Pharmacol. 2010 Nov;161(5):1059-69. doi: 10.1111/j.1476-5381.2010.00946.x.
51	Chronic imatinib mesylate exposure leads to reduced intracellular drug accumulation by induction of the ABCG2 (BCRP) and ABCB1 (MDR1) drug transport pumps. Cancer Biol Ther. 2005 Jul;4(7):747-52.
52	A systems biology understanding of the synergistic effects of arsenic sulfide and Imatinib in BCR/ABL-associated leukemia. Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3378-83.
53	Interference with bile salt export pump function is a susceptibility factor for human liver injury in drug development. Toxicol Sci. 2010 Dec; 118(2):485-500.
54	Anti-leukemic effects of gallic acid on human leukemia K562 cells: downregulation of COX-2, inhibition of BCR/ABL kinase and NF-B inactivation. Toxicol In Vitro. 2012 Apr;26(3):396-405.
55	Effects of Imatinib Mesylate (Gleevec) on human islet NF-kappaB activation and chemokine production in vitro. PLoS One. 2011;6(9):e24831. doi: 10.1371/journal.pone.0024831. Epub 2011 Sep 14.
56	Chemosensitization by STI571 targeting the platelet-derived growth factor/platelet-derived growth factor receptor-signaling pathway in the tumor progression and angiogenesis of gastric carcinoma. Cancer. 2005 May 1;103(9):1800-9. doi: 10.1002/cncr.20973.
57	Imatinib mesylate, a new kid on the block for the treatment of anti-neutrophil cytoplasmic autoantibodies-associated vasculitis?. Clin Exp Immunol. 2008 Mar;151(3):391-8. doi: 10.1111/j.1365-2249.2007.03572.x. Epub 2008 Jan 10.
58	Imatinib-induced hepatotoxicity via oxidative stress and activation of NLRP3 inflammasome: an in vitro and in vivo study. Arch Toxicol. 2022 Apr;96(4):1075-1087. doi: 10.1007/s00204-022-03245-x. Epub 2022 Feb 22.
59	Oral lichenoid eruption secondary to imatinib (Glivec). J Dermatolog Treat. 2004 Jul;15(4):253-5. doi: 10.1080/09546630410015556.
60	AMP-activated protein kinase activation primes cytoplasmic translocation and autophagic degradation of the BCR-ABL protein in CML cells. Cancer Sci. 2021 Jan;112(1):194-204. doi: 10.1111/cas.14698. Epub 2020 Nov 16.
61	Association of CYP1A1 and CYP1B1 inhibition in in vitro assays with drug-induced liver injury. J Toxicol Sci. 2021;46(4):167-176. doi: 10.2131/jts.46.167.
62	Imatinib mesylate inhibits T-cell proliferation in vitro and delayed-type hypersensitivity in vivo. Blood. 2004 Aug 15;104(4):1094-9. doi: 10.1182/blood-2003-12-4266. Epub 2004 Apr 20.
63	Dual inhibition of RET and FGFR4 restrains medullary thyroid cancer cell growth. Clin Cancer Res. 2005 Feb 1;11(3):1336-41.
64	Combination of imatinib and clotrimazole enhances cell growth inhibition in T47D breast cancer cells. Chem Biol Interact. 2015 May 25;233:147-56. doi: 10.1016/j.cbi.2015.03.028. Epub 2015 Apr 8.
65	Efficacy of the polo-like kinase inhibitor rigosertib, alone or in combination with Abelson tyrosine kinase inhibitors, against break point cluster region-c-Abelson-positive leukemia cells. Oncotarget. 2015 Aug 21;6(24):20231-40. doi: 10.18632/oncotarget.4047.
66	Saikosaponin D disrupts platelet-derived growth factor- receptor/p38 pathway leading to mitochondrial apoptosis in human LO2 hepatocyte cells: a potential mechanism of hepatotoxicity. Chem Biol Interact. 2013 Oct 25;206(1):76-82. doi: 10.1016/j.cbi.2013.08.006. Epub 2013 Aug 28.
67	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.
68	Proapoptotic activity of bortezomib in gastrointestinal stromal tumor cells. Cancer Res. 2010 Jan 1;70(1):150-9. doi: 10.1158/0008-5472.CAN-09-1449. Epub 2009 Dec 22.
69	The CML-related oncoprotein BCR/ABL induces expression of histidine decarboxylase (HDC) and the synthesis of histamine in leukemic cells. Blood. 2006 Nov 15;108(10):3538-47. doi: 10.1182/blood-2005-12-028456. Epub 2006 Jul 18.
70	Increased expression of fibroblast growth factor receptor 3 in CD34+ BCR-ABL+ cells from patients with chronic myeloid leukemia. Leukemia. 2003 Dec;17(12):2418-25. doi: 10.1038/sj.leu.2403152.
71	Cytotoxicity of 34 FDA approved small-molecule kinase inhibitors in primary rat and human hepatocytes. Toxicol Lett. 2018 Jul;291:138-148. doi: 10.1016/j.toxlet.2018.04.010. Epub 2018 Apr 12.
72	Anthelmintic Niclosamide Disrupts the Interplay of p65 and FOXM1/-catenin and Eradicates Leukemia Stem Cells in Chronic Myelogenous Leukemia. Clin Cancer Res. 2017 Feb 1;23(3):789-803. doi: 10.1158/1078-0432.CCR-16-0226. Epub 2016 Aug 4.
73	In vitro studies of the combination of imatinib mesylate (Gleevec) and arsenic trioxide (Trisenox) in chronic myelogenous leukemia. Exp Hematol. 2002 Jul;30(7):729-37. doi: 10.1016/s0301-472x(02)00836-6.
74	Establishment and characterization of a novel imatinib-sensitive chronic myeloid leukemia cell line MYL, and an imatinib-resistant subline MYL-R showing overexpression of Lyn. Eur J Haematol. 2007 May;78(5):417-31. doi: 10.1111/j.1600-0609.2007.00835.x.
75	The catalytic DNA topoisomerase II inhibitor dexrazoxane (ICRF-187) induces differentiation and apoptosis in human leukemia K562 cells. Mol Pharmacol. 2001 Mar;59(3):453-61. doi: 10.1124/mol.59.3.453.
76	Downregulation of hERG channel expression by tyrosine kinase inhibitors nilotinib and vandetanib predominantly contributes to arrhythmogenesis. Toxicol Lett. 2022 Jul 15;365:11-23. doi: 10.1016/j.toxlet.2022.06.001. Epub 2022 Jun 6.
77	Investigation of imatinib and other approved drugs as starting points for antidiabetic drug discovery with FXR modulating activity. Biochem Pharmacol. 2012 Jun 15;83(12):1674-81. doi: 10.1016/j.bcp.2012.02.027. Epub 2012 Mar 7.
78	A new strategy for the rapid identification and validation of direct toxicity targets of psoralen-induced hepatotoxicity. Toxicol Lett. 2022 Jun 15;363:11-26. doi: 10.1016/j.toxlet.2022.05.002. Epub 2022 May 18.
79	Sorafenib induces apoptosis specifically in cells expressing BCR/ABL by inhibiting its kinase activity to activate the intrinsic mitochondrial pathway. Cancer Res. 2009 May 1;69(9):3927-36. doi: 10.1158/0008-5472.CAN-08-2978. Epub 2009 Apr 14.
80	A high-throughput screen for teratogens using human pluripotent stem cells. Toxicol Sci. 2014 Jan;137(1):76-90. doi: 10.1093/toxsci/kft239. Epub 2013 Oct 23.
81	Denaturing-HPLC-based assay for detection of ABL mutations in chronic myeloid leukemia patients resistant to Imatinib. Clin Chem. 2004 Jul;50(7):1205-13. doi: 10.1373/clinchem.2004.031112. Epub 2004 Apr 23.
82	Identification of Genes That Modulate Susceptibility to Formaldehyde and Imatinib by Functional Genomic Screening in Human Haploid KBM7 Cells. Toxicol Sci. 2016 May;151(1):10-22. doi: 10.1093/toxsci/kfw032. Epub 2016 Mar 22.
83	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.
84	Disruption of the inhibitor of apoptosis protein survivin sensitizes Bcr-abl-positive cells to STI571-induced apoptosis. Cancer Res. 2005 Sep 15;65(18):8224-32. doi: 10.1158/0008-5472.CAN-05-0303.
85	Epigenetic down-regulation of BIM expression is associated with reduced optimal responses to imatinib treatment in chronic myeloid leukaemia. Eur J Cancer. 2009 Jul;45(10):1877-89. doi: 10.1016/j.ejca.2009.04.005. Epub 2009 May 4.
86	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.