Details of the Drug Combination

General Information of Drug Combination (ID: DC5IYT7)

• Drug Combination Name: Topotecan + Lapatinib
• Indication: Colon adenocarcinoma; Status: Investigative [1]
• Component Drugs:
  Topotecan (DMP6G8T): Small molecular drug
  Lapatinib (DM3BH1Y): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: LOVO
  Zero Interaction Potency (ZIP) Score: 4.59
  Bliss Independence Score: 4.07
  Loewe Additivity Score: 10.28
  LHighest Single Agent (HSA) Score: 12.52

Molecular Interaction Atlas of This Drug Combination

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]

Topotecan Interacts with 183 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]
Transcription factor Jun (JUN)	OTCYBO6X	JUN_HUMAN	Increases Phosphorylation	[19]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[20]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Expression	[21]
Methylated-DNA--protein-cysteine methyltransferase (MGMT)	OT40A9WH	MGMT_HUMAN	Decreases Expression	[22]
Tumor necrosis factor receptor superfamily member 6 (FAS)	OTP9XG86	TNR6_HUMAN	Decreases Expression	[23]
Catenin beta-1 (CTNNB1)	OTZ932A3	CTNB1_HUMAN	Increases Cleavage	[17]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[20]
Tumor protein 63 (TP63)	OT0WOOKQ	P63_HUMAN	Decreases Expression	[21]
Bcl-2-like protein 12 (BCL2L12)	OTS6IFZY	B2L12_HUMAN	Decreases Expression	[23]
Three-prime repair exonuclease 1 (TREX1)	OTQG7K12	TREX1_HUMAN	Increases Expression	[19]
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]
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]
Optineurin (OPTN)	OT2UXWH9	OPTN_HUMAN	Affects Response To Substance	[9]
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]
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]
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]
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]
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]
Calmodulin-regulated spectrin-associated protein 2 (CAMSAP2)	OT9KXWE7	CAMP2_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]
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]
Tetraspanin-13 (TSPAN13)	OTCS9BZY	TSN13_HUMAN	Affects Response To Substance	[9]
Tropomyosin alpha-1 chain (TPM1)	OTD73X6R	TPM1_HUMAN	Affects Response To Substance	[9]
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]
Ras-related protein Rab-7L1 (RAB29)	OTDZT6LP	RAB7L_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]
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]
Transmembrane protein 80 (TMEM80)	OTG9D4KX	TMM80_HUMAN	Affects Response To Substance	[9]
Cytotoxic granule associated RNA binding protein TIA1 (TIA1)	OTGPN3P8	TIA1_HUMAN	Affects Response To Substance	[9]
Epithelial cell adhesion molecule (EPCAM)	OTHBZK5X	EPCAM_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]
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]
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]
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]
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]
BH3-interacting domain death agonist (BID)	OTOSHSHU	BID_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]
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]
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]
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]
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]
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]
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]
Interleukin-1 receptor accessory protein-like 1 (IL1RAPL1)	OTW3T4B2	IRPL1_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]
Methyl-CpG-binding domain protein 4 (MBD4)	OTWR9YXE	MBD4_HUMAN	Affects Response To Substance	[9]
ORC ubiquitin ligase 1 (OBI1)	OTX62ZHW	OBI1_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]
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]

Indication(s) of Lapatinib

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Approved	[6]
Gastroesophageal junction adenocarcinoma	2B71	Approved	[7]
Melanoma	2C30	Approved	[7]

Lapatinib Interacts with 3 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Erbb2 tyrosine kinase receptor (HER2)	TT6EO5L	ERBB2_HUMAN	Inhibitor	[25]
Epidermal growth factor receptor (EGFR)	TTGKNB4	EGFR_HUMAN	Inhibitor	[25]
Eukaryotic elongation factor 2 kinase (eEF-2K)	TT1QFLA	EF2K_HUMAN	Inhibitor	[26]

Lapatinib Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[27]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[28]

Lapatinib Interacts with 4 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[29]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[30]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[29]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[30]

Lapatinib Interacts with 15 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[31]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Increases Expression	[32]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Expression	[33]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[34]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Expression	[35]
Phosphatidylcholine translocator ABCB4 (ABCB4)	OTE6PY83	MDR3_HUMAN	Decreases Activity	[36]
Receptor tyrosine-protein kinase erbB-3 (ERBB3)	OTRSST0A	ERBB3_HUMAN	Decreases Activity	[37]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Activity	[34]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Activity	[34]
Cyclin-dependent kinase inhibitor 1B (CDKN1B)	OTNY5LLZ	CDN1B_HUMAN	Increases Expression	[38]
HLA class II histocompatibility antigen, DQ alpha 1 chain (HLA-DQA1)	OTC6GISG	DQA1_HUMAN	Increases ADR	[39]
Zinc finger protein SNAI1 (SNAI1)	OTDPYAMC	SNAI1_HUMAN	Decreases Response To Substance	[40]
Transforming growth factor beta-1 proprotein (TGFB1)	OTV5XHVH	TGFB1_HUMAN	Decreases Response To Substance	[40]
Tenascin-X (TNXB)	OTVBWAV5	TENX_HUMAN	Increases ADR	[39]
HLA class II histocompatibility antigen, DQ beta 1 chain (HLA-DQB1)	OTVVI3UI	DQB1_HUMAN	Increases ADR	[39]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Breast and ovarian cancer syndrome	DC2PFRZ	UWB1289	Investigative	[1]
Breast and ovarian cancer syndrome	DCRZL02	UWB1289+BRCA1	Investigative	[1]
Carcinoma	DCXVPTH	MDAMB436	Investigative	[1]
Carcinoma	DCHTJVO	MCF7	Investigative	[1]
Colon carcinoma	DCHYCI4	RKO	Investigative	[1]
Adenocarcinoma	DCQ3W5L	CAOV3	Investigative	[41]
Adenocarcinoma	DCJPHFZ	A427	Investigative	[41]
Adenocarcinoma	DCQVINH	NCIH2122	Investigative	[41]
Adenocarcinoma	DCS485X	A549	Investigative	[41]
Adenocarcinoma	DCGB6G4	COLO320DM	Investigative	[41]
Adenocarcinoma	DCLJRLI	DLD1	Investigative	[41]
Adenocarcinoma	DCXVRJC	HCT116	Investigative	[41]
Adenocarcinoma	DC8X9XO	HT29	Investigative	[41]
Amelanotic melanoma	DCT6ZP7	A2058	Investigative	[41]
Astrocytoma	DCCHMAX	SNB-19	Investigative	[41]
Clear cell renal cell carcinoma	DC7EZMP	CAKI-1	Investigative	[41]
Cutaneous melanoma	DCVUTTJ	SK-MEL-28	Investigative	[41]
Ewing sarcoma-peripheral primitive neuroectodermal tumour	DCUCO7M	ES2	Investigative	[41]
Germ cell tumour	DC6DQRB	PA1	Investigative	[41]
Glioma	DCJQZTD	SF-268	Investigative	[41]
High grade ovarian serous adenocarcinoma	DC1O210	OVCAR-8	Investigative	[41]
Malignant melanoma	DCYOPYQ	RPMI7951	Investigative	[41]
Malignant melanoma	DCEGB43	SKMEL30	Investigative	[41]
Malignant melanoma	DCJ7NF1	UACC62	Investigative	[41]
Melanoma	DCYI29S	MALME-3M	Investigative	[41]
Minimally invasive lung adenocarcinoma	DCGJXJA	NCI-H322M	Investigative	[41]
Mixed endometrioid and clear cell carcinoma	DCBEKBF	IGROV1	Investigative	[41]
Ovarian endometrioid adenocarcinoma	DC4MBOD	A2780	Investigative	[41]
Ovarian serous cystadenocarcinoma	DCXH2KT	SK-OV-3	Investigative	[41]
Papillary renal cell carcinoma	DCL5U9T	ACHN	Investigative	[41]
Pleural epithelioid mesothelioma	DCMQJ51	NCI-H226	Investigative	[41]
Prostate carcinoma	DCQPSNL	VCAP	Investigative	[41]
Prostate carcinoma	DCQS5F5	PC-3	Investigative	[41]

References

• [1] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1126165
• [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: 5692).
• [7] Lapatinib FDA Label
• [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] 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.
• [20] 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.
• [21] 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.
• [22] 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.
• [23] 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.
• [24] UGT-dependent regioselective glucuronidation of ursodeoxycholic acid and obeticholic acid and selective transport of the consequent acyl glucuronides by OATP1B1 and 1B3. Chem Biol Interact. 2019 Sep 1;310:108745. doi: 10.1016/j.cbi.2019.108745. Epub 2019 Jul 9.
• [25] Triple negative breast cancer--current status and prospective targeted treatment based on HER1 (EGFR), TOP2A and C-MYC gene assessment. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2009 Mar;153(1):13-7.
• [26] Inhibition of eEF-2 kinase sensitizes human nasopharyngeal carcinoma cells to lapatinib-induced apoptosis through the Src and Erk pathways.BMC Cancer. 2016 Oct 19;16(1):813.
• [27] Tarascon Pocket Pharmacopoeia 2018 Classic Shirt-Pocket Edition.
• [28] The role of efflux and uptake transporters in [N-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-6-[5-({[2-(methylsulfonyl)ethyl]amino}methyl)-2-furyl]-4-quinazolinamine (GW572016, lapatinib) disposition and drug interactions. Drug Metab Dispos. 2008 Apr;36(4):695-701.
• [29] Mechanism-based inactivation of cytochrome P450 3A4 by lapatinib. Mol Pharmacol. 2010 Oct;78(4):693-703.
• [30] Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev. 2009 Dec;35(8):692-706.
• [31] 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.
• [32] P450 3A-catalyzed O-dealkylation of lapatinib induces mitochondrial stress and activates Nrf2. Chem Res Toxicol. 2016 May 16;29(5):784-96.
• [33] Combining lapatinib (GW572016), a small molecule inhibitor of ErbB1 and ErbB2 tyrosine kinases, with therapeutic anti-ErbB2 antibodies enhances apoptosis of ErbB2-overexpressing breast cancer cells. Oncogene. 2005 Sep 15;24(41):6213-21. doi: 10.1038/sj.onc.1208774.
• [34] CDK4/6 inhibition provides a potent adjunct to Her2-targeted therapies in preclinical breast cancer models. Genes Cancer. 2014 Jul;5(7-8):261-72. doi: 10.18632/genesandcancer.24.
• [35] The involvement of hepatic cytochrome P450s in the cytotoxicity of lapatinib. Toxicol Sci. 2023 Dec 21;197(1):69-78. doi: 10.1093/toxsci/kfad099.
• [36] Evaluating the Role of Multidrug Resistance Protein 3 (MDR3) Inhibition in Predicting Drug-Induced Liver Injury Using 125 Pharmaceuticals. Chem Res Toxicol. 2017 May 15;30(5):1219-1229. doi: 10.1021/acs.chemrestox.7b00048. Epub 2017 May 4.
• [37] Suppression of HER2/HER3-mediated growth of breast cancer cells with combinations of GDC-0941 PI3K inhibitor, trastuzumab, and pertuzumab. Clin Cancer Res. 2009 Jun 15;15(12):4147-56. doi: 10.1158/1078-0432.CCR-08-2814. Epub 2009 Jun 9.
• [38] The dual ErbB1/ErbB2 inhibitor, lapatinib (GW572016), cooperates with tamoxifen to inhibit both cell proliferation- and estrogen-dependent gene expression in antiestrogen-resistant breast cancer. Cancer Res. 2005 Jan 1;65(1):18-25.
• [39] HLA-DQA1*02:01 is a major risk factor for lapatinib-induced hepatotoxicity in women with advanced breast cancer. J Clin Oncol. 2011 Feb 20;29(6):667-73. doi: 10.1200/JCO.2010.31.3197. Epub 2011 Jan 18.
• [40] Niclosamide inhibits epithelial-mesenchymal transition and tumor growth in lapatinib-resistant human epidermal growth factor receptor 2-positive breast cancer. Int J Biochem Cell Biol. 2016 Feb;71:12-23. doi: 10.1016/j.biocel.2015.11.014. Epub 2015 Nov 28.
• [41] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125976