Details of the Drug Combination

General Information of Drug Combination (ID: DCETIPX)

• Drug Combination Name: Pentamidine + Topotecan
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Pentamidine (DMHZJCG): Small molecular drug
  Topotecan (DMP6G8T): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 1.38
  Bliss Independence Score: 1.38
  Loewe Additivity Score: 18.54
  LHighest Single Agent (HSA) Score: 18.56

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Pentamidine

Disease Entry	ICD 11	Status	REF
African trypanosomiasis	1F51	Approved	[2]
Fungal infection	1F29-1F2F	Approved	[3]
Pneumocystis pneumonia	CA40.20	Approved	[2]
Human immunodeficiency virus infection	1C62	Withdrawn from market	[4]

Pentamidine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Tryptase alpha/beta-1 (Tryptase)	TTM1TDX	TRYB1_HUMAN	Inhibitor	[10]

Pentamidine Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[11]

Pentamidine Interacts with 6 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[12]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[12]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[12]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[12]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[12]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[13]

Pentamidine Interacts with 16 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2C19 (CYP2C19)	OTFMJYYE	CP2CJ_HUMAN	Decreases Activity	[14]
Nuclear protein 1 (NUPR1)	OT4FU8C0	NUPR1_HUMAN	Increases Expression	[9]
Alpha-1-antichymotrypsin (SERPINA3)	OT9BP2S0	AACT_HUMAN	Increases Expression	[9]
Solute carrier family 2, facilitated glucose transporter member 3 (SLC2A3)	OT2HZK5M	GTR3_HUMAN	Decreases Expression	[9]
Inhibin beta E chain (INHBE)	OTOI2NYG	INHBE_HUMAN	Increases Expression	[9]
Nuclear receptor subfamily 0 group B member 2 (NR0B2)	OT7UVICX	NR0B2_HUMAN	Increases Expression	[9]
Fibronectin type III domain-containing protein 4 (FNDC4)	OTOQK0WK	FNDC4_HUMAN	Increases Expression	[9]
Protein DEPP1 (DEPP1)	OTB36PHJ	DEPP1_HUMAN	Increases Expression	[9]
Nibrin (NBN)	OT73B5MD	NBN_HUMAN	Affects Localization	[15]
HLA class II histocompatibility antigen, DQ beta 1 chain (HLA-DQB1)	OTVVI3UI	DQB1_HUMAN	Affects Expression	[16]
Interferon gamma receptor 1 (IFNGR1)	OTCTQBWW	INGR1_HUMAN	Increases Expression	[17]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Affects Localization	[15]
Double-strand break repair protein MRE11 (MRE11)	OTGU8TZM	MRE11_HUMAN	Decreases Activity	[15]
Serine-protein kinase ATM (ATM)	OTQVOHLT	ATM_HUMAN	Decreases Activity	[15]
Histone acetyltransferase KAT5 (KAT5)	OTL7257A	KAT5_HUMAN	Decreases Activity	[15]
Bile acid receptor (NR1H4)	OTWZLPTB	NR1H4_HUMAN	Increases Activity	[18]

Indication(s) of Topotecan

Disease Entry	ICD 11	Status	REF
Central nervous system neoplasm	N.A.	Approved	[5]
Cervical cancer	2C77.0	Approved	[5]
Epithelial ovarian cancer	2B5D	Approved	[5]
Lung cancer	2C25.0	Approved	[5]
Ovarian cancer	2C73	Approved	[6]
Solid tumour/cancer	2A00-2F9Z	Approved	[7]
Small-cell lung cancer	2C25.Y	Phase 1	[8]
Neuroblastoma	2D11.2	Investigative	[5]

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	[22]

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	[23]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[24]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[25]
Multidrug and toxin extrusion protein 1 (SLC47A1)	DTZGT0P	S47A1_HUMAN	Substrate	[26]
Multidrug resistance-associated protein 4 (ABCC4)	DTCSGPB	MRP4_HUMAN	Substrate	[27]
Multidrug and toxin extrusion protein 2 (SLC47A2)	DT3TX4H	S47A2_HUMAN	Substrate	[26]

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	[28]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2)	OTW8V2V1	ABCG2_HUMAN	Decreases Response To Substance	[29]
Transcription factor Jun (JUN)	OTCYBO6X	JUN_HUMAN	Increases Phosphorylation	[30]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[31]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Expression	[32]
Methylated-DNA--protein-cysteine methyltransferase (MGMT)	OT40A9WH	MGMT_HUMAN	Decreases Expression	[33]
Tumor necrosis factor receptor superfamily member 6 (FAS)	OTP9XG86	TNR6_HUMAN	Decreases Expression	[34]
Catenin beta-1 (CTNNB1)	OTZ932A3	CTNB1_HUMAN	Increases Cleavage	[28]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[31]
Tumor protein 63 (TP63)	OT0WOOKQ	P63_HUMAN	Decreases Expression	[32]
Bcl-2-like protein 12 (BCL2L12)	OTS6IFZY	B2L12_HUMAN	Decreases Expression	[34]
Three-prime repair exonuclease 1 (TREX1)	OTQG7K12	TREX1_HUMAN	Increases Expression	[30]
Histone H2A.V (H2AZ2)	OT0I5H2P	H2AV_HUMAN	Affects Response To Substance	[20]
Receptor-interacting serine/threonine-protein kinase 2 (RIPK2)	OT0KMIYQ	RIPK2_HUMAN	Affects Response To Substance	[20]
2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial (BCKDHA)	OT0LHOZB	ODBA_HUMAN	Affects Response To Substance	[20]
Secreted frizzled-related protein 1 (SFRP1)	OT0U9G41	SFRP1_HUMAN	Affects Response To Substance	[20]
Tripartite motif-containing protein 2 (TRIM2)	OT0V1YVC	TRIM2_HUMAN	Affects Response To Substance	[20]
Tetraspanin-8 (TSPAN8)	OT1F68WQ	TSN8_HUMAN	Affects Response To Substance	[20]
Tumor necrosis factor alpha-induced protein 8 (TNFAIP8)	OT1G9297	TFIP8_HUMAN	Affects Response To Substance	[20]
Optineurin (OPTN)	OT2UXWH9	OPTN_HUMAN	Affects Response To Substance	[20]
Protein FAM171A1 (FAM171A1)	OT33BHEP	F1711_HUMAN	Affects Response To Substance	[20]
Filamin-C (FLNC)	OT3F8J6Y	FLNC_HUMAN	Affects Response To Substance	[20]
Cleavage stimulation factor subunit 2 tau variant (CSTF2T)	OT3IKRL2	CSTFT_HUMAN	Affects Response To Substance	[20]
Fatty acid CoA ligase Acsl3 (ACSL3)	OT3MWER1	ACSL3_HUMAN	Affects Response To Substance	[20]
Peptidyl-prolyl cis-trans isomerase NIMA-interacting 4 (PIN4)	OT403QC1	PIN4_HUMAN	Affects Response To Substance	[20]
C-Jun-amino-terminal kinase-interacting protein 4 (SPAG9)	OT45AHMB	JIP4_HUMAN	Affects Response To Substance	[20]
Sorcin (SRI)	OT4R3EAC	SORCN_HUMAN	Affects Response To Substance	[20]
High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A (PDE8A)	OT4RF9Z4	PDE8A_HUMAN	Affects Response To Substance	[20]
Argininosuccinate synthase (ASS1)	OT4ZMG0Q	ASSY_HUMAN	Affects Response To Substance	[20]
Polyphosphoinositide phosphatase (FIG4)	OT501PY9	FIG4_HUMAN	Affects Response To Substance	[20]
Ubiquitin-like protein ISG15 (ISG15)	OT53QQ7N	ISG15_HUMAN	Affects Response To Substance	[20]
Leukocyte elastase inhibitor (SERPINB1)	OT5RDUFO	ILEU_HUMAN	Affects Response To Substance	[20]
Collagen alpha-2(V) chain (COL5A2)	OT5VOSQE	CO5A2_HUMAN	Decreases Response To Substance	[21]
Transcription activator BRG1 (SMARCA4)	OT68WOPQ	SMCA4_HUMAN	Affects Response To Substance	[20]
Metal cation symporter ZIP8 (SLC39A8)	OT6C6MNV	S39A8_HUMAN	Affects Response To Substance	[20]
Regulator of G-protein signaling 20 (RGS20)	OT6CGYHW	RGS20_HUMAN	Affects Response To Substance	[20]
BTB/POZ domain-containing protein KCTD3 (KCTD3)	OT6EGR42	KCTD3_HUMAN	Affects Response To Substance	[20]
Melanoma-associated antigen D1 (MAGED1)	OT6EOLFC	MAGD1_HUMAN	Affects Response To Substance	[20]
Ferritin heavy chain (FTH1)	OT6IFS0O	FRIH_HUMAN	Affects Response To Substance	[20]
Protein-glutamine gamma-glutamyltransferase 2 (TGM2)	OT6MFOWF	TGM2_HUMAN	Affects Response To Substance	[20]
G-protein-signaling modulator 2 (GPSM2)	OT6RPMRM	GPSM2_HUMAN	Affects Response To Substance	[20]
Cytochrome b5 (CYB5A)	OT6SN4RM	CYB5_HUMAN	Affects Response To Substance	[20]
Ankycorbin (RAI14)	OT6USGBK	RAI14_HUMAN	Affects Response To Substance	[20]
Plasminogen activator inhibitor 2 (SERPINB2)	OT72QLZB	PAI2_HUMAN	Affects Response To Substance	[20]
Replication protein A 70 kDa DNA-binding subunit (RPA1)	OT76POLP	RFA1_HUMAN	Affects Response To Substance	[20]
Signal transducer CD24 (CD24)	OT7CODJ4	CD24_HUMAN	Affects Response To Substance	[20]
Polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3)	OT7M67WT	GALT3_HUMAN	Affects Response To Substance	[20]
Forkhead box protein D1 (FOXD1)	OT80PRHS	FOXD1_HUMAN	Affects Response To Substance	[20]
Cbp/p300-interacting transactivator 2 (CITED2)	OT812TV7	CITE2_HUMAN	Affects Response To Substance	[20]
Raftlin (RFTN1)	OT8875JE	RFTN1_HUMAN	Affects Response To Substance	[20]
Mesoderm-specific transcript homolog protein (MEST)	OT8Q4U8Y	MEST_HUMAN	Affects Response To Substance	[20]
Four-jointed box protein 1 (FJX1)	OT8SVTSS	FJX1_HUMAN	Affects Response To Substance	[20]
Calmodulin-regulated spectrin-associated protein 2 (CAMSAP2)	OT9KXWE7	CAMP2_HUMAN	Affects Response To Substance	[20]
High mobility group nucleosome-binding domain-containing protein 3 (HMGN3)	OTA2TBWS	HMGN3_HUMAN	Affects Response To Substance	[20]
Diphosphoinositol polyphosphate phosphohydrolase NUDT4B (NUDT4)	OTA6ICI2	NUD4B_HUMAN	Affects Response To Substance	[20]
SEC14-like protein 1 (SEC14L1)	OTA75FET	S14L1_HUMAN	Affects Response To Substance	[20]
Autism susceptibility gene 2 protein (AUTS2)	OTAEXHSC	AUTS2_HUMAN	Affects Response To Substance	[20]
Grancalcin (GCA)	OTAJ7ZHG	GRAN_HUMAN	Affects Response To Substance	[20]
RNA polymerase II elongation factor ELL3 (ELL3)	OTALC1YD	ELL3_HUMAN	Affects Response To Substance	[20]
Receptor-type tyrosine-protein phosphatase kappa (PTPRK)	OTAP5AT3	PTPRK_HUMAN	Affects Response To Substance	[20]
snRNA-activating protein complex subunit 1 (SNAPC1)	OTAPN1NI	SNPC1_HUMAN	Affects Response To Substance	[20]
Cyclin-dependent kinase inhibitor 1C (CDKN1C)	OTASTJ3Q	CDN1C_HUMAN	Affects Response To Substance	[20]
Stearoyl-CoA desaturase (SCD)	OTB1073G	SCD_HUMAN	Affects Response To Substance	[20]
Desmoplakin (DSP)	OTB2MOP8	DESP_HUMAN	Affects Response To Substance	[20]
Protein lin-7 homolog C (LIN7C)	OTB3015O	LIN7C_HUMAN	Affects Response To Substance	[20]
Heterogeneous nuclear ribonucleoprotein D-like (HNRNPDL)	OTB3BFCV	HNRDL_HUMAN	Affects Response To Substance	[20]
Microtubule-associated tumor suppressor 1 (MTUS1)	OTBPALMU	MTUS1_HUMAN	Affects Response To Substance	[20]
Cilium assembly protein DZIP1 (DZIP1)	OTBVPO66	DZIP1_HUMAN	Affects Response To Substance	[20]
Thiamin pyrophosphokinase 1 (TPK1)	OTCHPUD0	TPK1_HUMAN	Affects Response To Substance	[20]
Cytoskeleton-associated protein 2 (CKAP2)	OTCLTC0J	CKAP2_HUMAN	Affects Response To Substance	[20]
Hydroxymethylglutaryl-CoA synthase, cytoplasmic (HMGCS1)	OTCO26FV	HMCS1_HUMAN	Affects Response To Substance	[20]
Tetraspanin-13 (TSPAN13)	OTCS9BZY	TSN13_HUMAN	Affects Response To Substance	[20]
Tropomyosin alpha-1 chain (TPM1)	OTD73X6R	TPM1_HUMAN	Affects Response To Substance	[20]
AP-5 complex subunit mu-1 (AP5M1)	OTDLWEBL	AP5M1_HUMAN	Affects Response To Substance	[20]
Protein eva-1 homolog B (EVA1B)	OTDNAKQD	EVA1B_HUMAN	Affects Response To Substance	[20]
Gamma-adducin (ADD3)	OTDRSHAZ	ADDG_HUMAN	Affects Response To Substance	[20]
Ras-related protein Rab-7L1 (RAB29)	OTDZT6LP	RAB7L_HUMAN	Affects Response To Substance	[20]
H(+)/Cl(-) exchange transporter 3 (CLCN3)	OTEEXNMU	CLCN3_HUMAN	Affects Response To Substance	[20]
Secernin-1 (SCRN1)	OTELM5C2	SCRN1_HUMAN	Affects Response To Substance	[20]
NGFI-A-binding protein 1 (NAB1)	OTEWHIZR	NAB1_HUMAN	Affects Response To Substance	[20]
Solute carrier family 35 member G2 (SLC35G2)	OTFBVS0P	S35G2_HUMAN	Affects Response To Substance	[20]
Cadherin-1 (CDH1)	OTFJMXPM	CADH1_HUMAN	Affects Response To Substance	[20]
Multiple C2 and transmembrane domain-containing protein 2 (MCTP2)	OTFMZ8I2	MCTP2_HUMAN	Affects Response To Substance	[20]
Caveolae-associated protein 1 (CAVIN1)	OTFO915U	CAVN1_HUMAN	Affects Response To Substance	[20]
Laminin subunit alpha-2 (LAMA2)	OTFROQWE	LAMA2_HUMAN	Increases Response To Substance	[21]
Centriolar satellite-associated tubulin polyglutamylase complex regulator 1 (CSTPP1)	OTFSO3XV	CSTP1_HUMAN	Affects Response To Substance	[20]
Baculoviral IAP repeat-containing protein 2 (BIRC2)	OTFXFREP	BIRC2_HUMAN	Affects Response To Substance	[20]
Transmembrane protein 80 (TMEM80)	OTG9D4KX	TMM80_HUMAN	Affects Response To Substance	[20]
Cytotoxic granule associated RNA binding protein TIA1 (TIA1)	OTGPN3P8	TIA1_HUMAN	Affects Response To Substance	[20]
Epithelial cell adhesion molecule (EPCAM)	OTHBZK5X	EPCAM_HUMAN	Affects Response To Substance	[20]
DNA damage-inducible transcript 4 protein (DDIT4)	OTHY8SY4	DDIT4_HUMAN	Affects Response To Substance	[20]
Interstitial collagenase (MMP1)	OTI4I2V1	MMP1_HUMAN	Affects Response To Substance	[20]
Solute carrier family 38 member 6 (SLC38A6)	OTIC8SHQ	S38A6_HUMAN	Affects Response To Substance	[20]
G2/mitotic-specific cyclin-B2 (CCNB2)	OTIEXTDK	CCNB2_HUMAN	Affects Response To Substance	[20]
Laminin subunit gamma-1 (LAMC1)	OTIG527N	LAMC1_HUMAN	Affects Response To Substance	[20]
Cyclin-G2 (CCNG2)	OTII38K2	CCNG2_HUMAN	Affects Response To Substance	[20]
Beta/gamma crystallin domain-containing protein 1 (CRYBG1)	OTIPDI15	CRBG1_HUMAN	Affects Response To Substance	[20]
Ras-related protein Rab-13 (RAB13)	OTIQ484I	RAB13_HUMAN	Affects Response To Substance	[20]
Ankyrin repeat domain-containing protein 10 (ANKRD10)	OTIZ2VK8	ANR10_HUMAN	Affects Response To Substance	[20]
Histone deacetylase complex subunit SAP18 (SAP18)	OTJAZWOL	SAP18_HUMAN	Affects Response To Substance	[20]
E3 ubiquitin-protein ligase FANCL (FANCL)	OTJC7QPQ	FANCL_HUMAN	Affects Response To Substance	[20]
Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial (HADH)	OTJDOL20	HCDH_HUMAN	Affects Response To Substance	[20]
FERM domain-containing protein 4A (FRMD4A)	OTJDTIK2	FRM4A_HUMAN	Affects Response To Substance	[20]
Cyclin-F (CCNF)	OTJFVU43	CCNF_HUMAN	Affects Response To Substance	[20]
Jupiter microtubule associated homolog 2 (JPT2)	OTJGPA4T	JUPI2_HUMAN	Affects Response To Substance	[20]
TBC1 domain family member 4 (TBC1D4)	OTK66C40	TBCD4_HUMAN	Affects Response To Substance	[20]
Tumor necrosis factor receptor superfamily member 6B (TNFRSF6B)	OTKAN9G7	TNF6B_HUMAN	Affects Response To Substance	[20]
Myelin protein zero-like protein 2 (MPZL2)	OTKFNDUI	MPZL2_HUMAN	Affects Response To Substance	[20]
Transmembrane channel-like protein 6 (TMC6)	OTKH50J4	TMC6_HUMAN	Affects Response To Substance	[20]
Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2)	OTKOZRZP	PLOD2_HUMAN	Affects Response To Substance	[20]
Enolase-phosphatase E1 (ENOPH1)	OTKXMWNN	ENOPH_HUMAN	Affects Response To Substance	[20]
Calcium-binding tyrosine phosphorylation-regulated protein (CABYR)	OTKYMT99	CABYR_HUMAN	Affects Response To Substance	[20]
Glycylpeptide N-tetradecanoyltransferase 2 (NMT2)	OTLNA39Z	NMT2_HUMAN	Affects Response To Substance	[20]
Hemicentin-1 (HMCN1)	OTLZAS0P	HMCN1_HUMAN	Increases Response To Substance	[21]
Ribosome biogenesis protein BOP1 (BOP1)	OTMZMQDO	BOP1_HUMAN	Affects Response To Substance	[20]
Eukaryotic peptide chain release factor GTP-binding subunit ERF3B (GSPT2)	OTN0K7F3	ERF3B_HUMAN	Affects Response To Substance	[20]
Four and a half LIM domains protein 1 (FHL1)	OTN535SU	FHL1_HUMAN	Affects Response To Substance	[20]
MAP kinase-interacting serine/threonine-protein kinase 2 (MKNK2)	OTNA9G8V	MKNK2_HUMAN	Affects Response To Substance	[20]
Epithelial splicing regulatory protein 1 (ESRP1)	OTNCS4SL	ESRP1_HUMAN	Affects Response To Substance	[20]
Radixin (RDX)	OTNSYUN6	RADI_HUMAN	Affects Response To Substance	[20]
Calcium-activated potassium channel subunit alpha-1 (KCNMA1)	OTNYXOZO	KCMA1_HUMAN	Affects Response To Substance	[20]
Paraneoplastic antigen-like protein 8A (PNMA8A)	OTO3F7B0	PNM8A_HUMAN	Affects Response To Substance	[20]
Polypeptide N-acetylgalactosaminyltransferase 1 (GALNT1)	OTO3RO36	GALT1_HUMAN	Affects Response To Substance	[20]
BH3-interacting domain death agonist (BID)	OTOSHSHU	BID_HUMAN	Affects Response To Substance	[20]
Unconventional myosin-Id (MYO1D)	OTP2RGPN	MYO1D_HUMAN	Affects Response To Substance	[20]
Rho GTPase-activating protein 7 (DLC1)	OTP8LMCR	RHG07_HUMAN	Affects Response To Substance	[20]
Ras-related protein Rab-20 (RAB20)	OTP9OOVS	RAB20_HUMAN	Affects Response To Substance	[20]
Dual specificity protein phosphatase 3 (DUSP3)	OTPJX9B4	DUS3_HUMAN	Affects Response To Substance	[20]
DNA dC->dU-editing enzyme APOBEC-3C (APOBEC3C)	OTPL0AI1	ABC3C_HUMAN	Affects Response To Substance	[20]
Pentraxin-related protein PTX3 (PTX3)	OTPXHRKU	PTX3_HUMAN	Affects Response To Substance	[20]
Dermatan-sulfate epimerase (DSE)	OTQ108VJ	DSE_HUMAN	Affects Response To Substance	[20]
Centromere protein U (CENPU)	OTQ4TZRS	CENPU_HUMAN	Affects Response To Substance	[20]
Sortilin-related receptor (SORL1)	OTQ8FFNS	SORL_HUMAN	Affects Response To Substance	[20]
Collagen alpha-2(VI) chain (COL6A2)	OTQC6PPO	CO6A2_HUMAN	Affects Response To Substance	[20]
Ran-specific GTPase-activating protein (RANBP1)	OTQE226K	RANG_HUMAN	Affects Response To Substance	[20]
MAPK/MAK/MRK overlapping kinase (MOK)	OTQK7M9V	MOK_HUMAN	Affects Response To Substance	[20]
Keratin, type I cytoskeletal 23 (KRT23)	OTQW6UAG	K1C23_HUMAN	Increases Response To Substance	[21]
Transforming growth factor-beta-induced protein ig-h3 (TGFBI)	OTR443C5	BGH3_HUMAN	Decreases Response To Substance	[21]
Large ribosomal subunit protein mL63 (MRPL57)	OTRB659E	RT63_HUMAN	Affects Response To Substance	[20]
Actin, gamma-enteric smooth muscle (ACTG2)	OTRDWUO0	ACTH_HUMAN	Affects Response To Substance	[20]
Acidic leucine-rich nuclear phosphoprotein 32 family member A (ANP32A)	OTRHPFO2	AN32A_HUMAN	Affects Response To Substance	[20]
Calcium/calmodulin-dependent protein kinase type 1 (CAMK1)	OTRN55RE	KCC1A_HUMAN	Affects Response To Substance	[20]
Receptor tyrosine-protein kinase erbB-3 (ERBB3)	OTRSST0A	ERBB3_HUMAN	Affects Response To Substance	[20]
Arginine and glutamate-rich protein 1 (ARGLU1)	OTRVRZ4Z	ARGL1_HUMAN	Affects Response To Substance	[20]
Dr1-associated corepressor (DRAP1)	OTRWLF6D	NC2A_HUMAN	Affects Response To Substance	[20]
Latent-transforming growth factor beta-binding protein 2 (LTBP2)	OTS88GSD	LTBP2_HUMAN	Affects Response To Substance	[20]
Heat shock-related 70 kDa protein 2 (HSPA2)	OTSDET7B	HSP72_HUMAN	Affects Response To Substance	[20]
Lumican (LUM)	OTSRC874	LUM_HUMAN	Decreases Response To Substance	[21]
GTP-binding protein SAR1a (SAR1A)	OTSSRVGV	SAR1A_HUMAN	Affects Response To Substance	[20]
Plasminogen activator inhibitor 1 (SERPINE1)	OTT0MPQ3	PAI1_HUMAN	Affects Response To Substance	[20]
Collagen alpha-1(III) chain (COL3A1)	OTT1EMLM	CO3A1_HUMAN	Decreases Response To Substance	[21]
KH domain-containing RNA-binding protein QKI (QKI)	OTTAUGLB	QKI_HUMAN	Affects Response To Substance	[20]
Cullin-4A (CUL4A)	OTTBV70J	CUL4A_HUMAN	Affects Response To Substance	[20]
Homeobox protein Hox-B2 (HOXB2)	OTTD6HMV	HXB2_HUMAN	Affects Response To Substance	[20]
Collagen alpha-1(XV) chain (COL15A1)	OTTFKK18	COFA1_HUMAN	Decreases Response To Substance	[21]
A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1)	OTTLJH8W	ATS1_HUMAN	Affects Response To Substance	[20]
Nuclear receptor-interacting protein 3 (NRIP3)	OTU15GMK	NRIP3_HUMAN	Affects Response To Substance	[20]
Granulocyte-macrophage colony-stimulating factor receptor subunit alpha (CSF2RA)	OTUOO2XS	CSF2R_HUMAN	Affects Response To Substance	[20]
La-related protein 6 (LARP6)	OTUQ9QS9	LARP6_HUMAN	Affects Response To Substance	[20]
General transcription factor II-I (GTF2I)	OTUYL1TQ	GTF2I_HUMAN	Affects Response To Substance	[20]
Protein aurora borealis (BORA)	OTV2ZPKP	BORA_HUMAN	Affects Response To Substance	[20]
FYVE, RhoGEF and PH domain-containing protein 1 (FGD1)	OTV3T64P	FGD1_HUMAN	Affects Response To Substance	[20]
Matrilin-2 (MATN2)	OTVDR68G	MATN2_HUMAN	Decreases Response To Substance	[21]
Microtubule-actin cross-linking factor 1, isoforms 1/2/3/4/5 (MACF1)	OTVIHD77	MACF1_HUMAN	Affects Response To Substance	[20]
Serine protease FAM111A (FAM111A)	OTVLARLG	F111A_HUMAN	Affects Response To Substance	[20]
Interleukin-1 receptor accessory protein-like 1 (IL1RAPL1)	OTW3T4B2	IRPL1_HUMAN	Affects Response To Substance	[20]
Tissue alpha-L-fucosidase (FUCA1)	OTW71IK4	FUCO_HUMAN	Affects Response To Substance	[20]
Fanconi anemia group I protein (FANCI)	OTW8E3SC	FANCI_HUMAN	Affects Response To Substance	[20]
U2 small nuclear ribonucleoprotein A' (SNRPA1)	OTWJZFAP	RU2A_HUMAN	Affects Response To Substance	[20]
Methyl-CpG-binding domain protein 4 (MBD4)	OTWR9YXE	MBD4_HUMAN	Affects Response To Substance	[20]
ORC ubiquitin ligase 1 (OBI1)	OTX62ZHW	OBI1_HUMAN	Affects Response To Substance	[20]
Condensin complex subunit 2 (NCAPH)	OTXOS97C	CND2_HUMAN	Affects Response To Substance	[20]
Collagen alpha-2(I) chain (COL1A2)	OTY7G382	CO1A2_HUMAN	Increases Response To Substance	[21]
Collagen alpha-1(VI) chain (COL6A1)	OTYKSCOB	CO6A1_HUMAN	Affects Response To Substance	[20]
Protein FAN (NSMAF)	OTYNVZ23	FAN_HUMAN	Affects Response To Substance	[20]
Protein Niban 1 (NIBAN1)	OTYOLI12	NIBA1_HUMAN	Affects Response To Substance	[20]
Nucleolar complex protein 3 homolog (NOC3L)	OTYOR3PV	NOC3L_HUMAN	Affects Response To Substance	[20]
Acetyl-CoA acetyltransferase, cytosolic (ACAT2)	OTZ092ZJ	THIC_HUMAN	Affects Response To Substance	[20]
Thiosulfate sulfurtransferase (TST)	OTZ4F5LK	THTR_HUMAN	Affects Response To Substance	[20]
Tissue factor pathway inhibitor 2 (TFPI2)	OTZCRWOR	TFPI2_HUMAN	Affects Response To Substance	[20]
Insulin-induced gene 1 protein (INSIG1)	OTZF5X1D	INSI1_HUMAN	Affects Response To Substance	[20]
Suppressor of tumorigenicity 7 protein (ST7)	OTZG8RC6	ST7_HUMAN	Affects Response To Substance	[20]
Fermitin family homolog 2 (FERMT2)	OTZNPWWX	FERM2_HUMAN	Affects Response To Substance	[20]

References

• [1] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
• [2] Pentamidine FDA Label
• [3] Opportunities and challenges in antiparasitic drug discovery. Nat Rev Drug Discov. 2005 Sep;4(9):727-40.
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [5] Topotecan FDA Label
• [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: 7101).
• [7] Plant-derived compounds in clinical trials. Drug Discov Today. 2008 Feb;13(3-4):161-71.
• [8] 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.
• [9] A toxicogenomic approach to drug-induced phospholipidosis: analysis of its induction mechanism and establishment of a novel in vitro screening system. Toxicol Sci. 2005 Feb;83(2):282-92.
• [10] Inhibitors of tryptase for the treatment of mast cell-mediated diseases. Curr Pharm Des. 1998 Oct;4(5):381-96.
• [11] Transport of dicationic drugs pentamidine and furamidine by human organic cation transporters. Drug Metab Dispos. 2009 Feb;37(2):424-30.
• [12] Identification of human cytochrome P(450)s that metabolise anti-parasitic drugs and predictions of in vivo drug hepatic clearance from in vitro data. Eur J Clin Pharmacol. 2003 Sep;59(5-6):429-42.
• [13] Value of preemptive CYP2C19 genotyping in allogeneic stem cell transplant patients considered for pentamidine administration. Clin Transplant. 2011 May-Jun;25(3):E271-5.
• [14] Application of higher throughput screening (HTS) inhibition assays to evaluate the interaction of antiparasitic drugs with cytochrome P450s. Drug Metab Dispos. 2001 Jan;29(1):30-5.
• [15] Bisbenzamidine derivative, pentamidine represses DNA damage response through inhibition of histone H2A acetylation. Mol Cancer. 2010 Feb 9;9:34. doi: 10.1186/1476-4598-9-34.
• [16] Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis. Chem Res Toxicol. 2015 May 18;28(5):927-34. doi: 10.1021/tx5005248. Epub 2015 Apr 3.
• [17] Antileishmanial drugs cause up-regulation of interferon-gamma receptor 1, not only in the monocytes of visceral leishmaniasis cases but also in cultured THP1 cells. Ann Trop Med Parasitol. 2003 Apr;97(3):245-57. doi: 10.1179/000349803235001714.
• [18] 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.
• [19] 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.
• [20] 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.
• [21] 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.
• [22] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [23] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [24] 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.
• [25] 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.
• [26] 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.
• [27] Topotecan is a substrate for multidrug resistance associated protein 4. Curr Drug Metab. 2006 Jan;7(1):105-18.
• [28] 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.
• [29] 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.
• [30] 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.
• [31] 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.
• [32] 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.
• [33] 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.
• [34] Topotecan and methotrexate alter expression of the apoptosis-related genes BCL2, FAS and BCL2L12 in leukemic HL-60 cells. Biol Chem. 2006 Dec;387(12):1629-33. doi: 10.1515/BC.2006.203.