Details of the Drug Combination

General Information of Drug Combination (ID: DCA8Z72)

• Drug Combination Name: Sulindac + Idarubicin
• Indication: Glioblastoma?; Status: Investigative [1]
• Component Drugs:
  Sulindac (DM2QHZU): Small molecular drug
  Idarubicin (DMM0XGL): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: T98G
  Zero Interaction Potency (ZIP) Score: 21.72
  Bliss Independence Score: 21.72
  Loewe Additivity Score: 10.82
  LHighest Single Agent (HSA) Score: 10.82

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Sulindac

Disease Entry	ICD 11	Status	REF
Acute myelogenous leukaemia	2A41	Approved	[2]
Bursitis	N.A.	Approved	[2]
Osteoarthritis	FA00-FA05	Approved	[2]
Rheumatoid arthritis	FA20	Approved	[3]
Colon cancer	2B90.Z	Investigative	[2]

Sulindac Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Aldose reductase (AKR1B1)	TTFBNVI	ALDR_HUMAN	Inhibitor	[10]

Sulindac Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 4 (ABCC4)	DTCSGPB	MRP4_HUMAN	Substrate	[11]

Sulindac Interacts with 135 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Putative glutamine amidotransferase-like class 1 domain-containing protein 3B, mitochondrial (GATD3)	OTBQRU82	GAL3B_HUMAN	Decreases Expression	[6]
Endosome/lysosome-associated apoptosis and autophagy regulator family member 2 (ELAPOR2)	OTL628I1	ELAP2_HUMAN	Increases Expression	[6]
Protocadherin-17 (PCDH17)	OTRK0M05	PCD17_HUMAN	Decreases Expression	[6]
Sarcoplasmic/endoplasmic reticulum calcium ATPase 1 (ATP2A1)	OT959A3A	AT2A1_HUMAN	Decreases Expression	[6]
NPC intracellular cholesterol transporter 1 (NPC1)	OTRIPICX	NPC1_HUMAN	Increases Expression	[6]
T-box transcription factor TBX3 (TBX3)	OTM64N7K	TBX3_HUMAN	Increases Expression	[6]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Expression	[6]
Monocarboxylate transporter 7 (SLC16A6)	OT7BIIZX	MOT7_HUMAN	Increases Expression	[6]
Origin recognition complex subunit 4 (ORC4)	OT3ACTST	ORC4_HUMAN	Decreases Expression	[6]
Transmembrane protein 127 (TMEM127)	OTYHUXC1	TM127_HUMAN	Increases Expression	[6]
Hyaluronan mediated motility receptor (HMMR)	OT4M0JTZ	HMMR_HUMAN	Decreases Expression	[6]
Ribonuclease pancreatic (RNASE1)	OTKZ7CO9	RNAS1_HUMAN	Decreases Expression	[6]
Amino acid transporter heavy chain SLC3A2 (SLC3A2)	OTBR33M9	4F2_HUMAN	Increases Expression	[6]
Lysosomal acid phosphatase (ACP2)	OTLPA1LJ	PPAL_HUMAN	Increases Expression	[6]
Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial (MTHFD2)	OT1LQSGX	MTDC_HUMAN	Increases Expression	[6]
Transcription factor JunD (JUND)	OTNKACJD	JUND_HUMAN	Increases Expression	[6]
Cyclic AMP-dependent transcription factor ATF-4 (ATF4)	OTRFV19J	ATF4_HUMAN	Increases Expression	[6]
Growth arrest and DNA damage-inducible protein GADD45 alpha (GADD45A)	OTDRV63V	GA45A_HUMAN	Increases Expression	[6]
DNA excision repair protein ERCC-5 (ERCC5)	OTQAKFJM	ERCC5_HUMAN	Decreases Expression	[6]
Biotin--protein ligase (HLCS)	OTPDUX30	BPL1_HUMAN	Decreases Expression	[6]
Plexin-A3 (PLXNA3)	OTMZIBVG	PLXA3_HUMAN	Increases Expression	[6]
Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 2 (NDST2)	OT21PY3J	NDST2_HUMAN	Decreases Expression	[6]
Small ubiquitin-related modifier 3 (SUMO3)	OTTUJQJ1	SUMO3_HUMAN	Decreases Expression	[6]
Histone H4 (H4C1)	OTB71W46	H4_HUMAN	Increases Expression	[6]
Casein kinase II subunit alpha (CSNK2A1)	OT9T8WQM	CSK21_HUMAN	Decreases Expression	[6]
Polycystin-1 (PKD1)	OT5ALRZ5	PKD1_HUMAN	Increases Expression	[6]
Transcription initiation factor IIB (GTF2B)	OTAH5NSO	TF2B_HUMAN	Increases Expression	[6]
Cdc42 effector protein 1 (CDC42EP1)	OTT525WA	BORG5_HUMAN	Increases Expression	[6]
Growth factor receptor-bound protein 10 (GRB10)	OTCKXGRC	GRB10_HUMAN	Increases Expression	[6]
Krueppel-like factor 5 (KLF5)	OT1ABI9N	KLF5_HUMAN	Increases Expression	[6]
Dihydropyrimidinase (DPYS)	OTLTUIVL	DPYS_HUMAN	Increases Expression	[6]
Four and a half LIM domains protein 2 (FHL2)	OT0OAYWT	FHL2_HUMAN	Increases Expression	[6]
Endoplasmic reticulum membrane sensor NFE2L1 (NFE2L1)	OT1QHOS2	NF2L1_HUMAN	Increases Expression	[6]
Kinesin-like protein KIF14 (KIF14)	OTXHT4JM	KIF14_HUMAN	Increases Expression	[6]
Syntaxin-binding protein 2 (STXBP2)	OTX8GUC4	STXB2_HUMAN	Increases Expression	[6]
Nuclear factor interleukin-3-regulated protein (NFIL3)	OTQH9HM3	NFIL3_HUMAN	Increases Expression	[6]
Phosphoenolpyruvate carboxykinase , mitochondrial (PCK2)	OTJ8LX4N	PCKGM_HUMAN	Increases Expression	[6]
TBC1 domain family member 10B (TBC1D10B)	OT5MVCI5	TB10B_HUMAN	Increases Expression	[6]
Migration and invasion-inhibitory protein (MIIP)	OT79EXZ7	MIIP_HUMAN	Increases Expression	[6]
Cyclin-J (CCNJ)	OTCR4WVV	CCNJ_HUMAN	Decreases Expression	[6]
OTU domain-containing protein 1 (OTUD1)	OTE6O5XB	OTUD1_HUMAN	Increases Expression	[6]
Tensin-3 (TNS3)	OTPG2D8Z	TENS3_HUMAN	Decreases Expression	[6]
F-box only protein 42 (FBXO42)	OTHPN53C	FBX42_HUMAN	Increases Expression	[6]
Metal transporter CNNM4 (CNNM4)	OTUXJRM1	CNNM4_HUMAN	Increases Expression	[6]
Ankyrin repeat domain-containing protein 11 (ANKRD11)	OTV0V70M	ANR11_HUMAN	Increases Expression	[6]
La-related protein 4 (LARP4)	OTB10IJH	LARP4_HUMAN	Increases Expression	[6]
LIM domain-binding protein 1 (LDB1)	OT20EAPR	LDB1_HUMAN	Increases Expression	[6]
Transmembrane protein adipocyte-associated 1 (TPRA1)	OTL61503	TPRA1_HUMAN	Increases Expression	[6]
Mitogen-activated protein kinase kinase kinase kinase 3 (MAP4K3)	OTNJX38T	M4K3_HUMAN	Increases Expression	[6]
UPF0690 protein C1orf52 (C1ORF52)	OT8RQW3W	CA052_HUMAN	Increases Expression	[6]
Beta-1,3-N-acetylglucosaminyltransferase lunatic fringe (LFNG)	OTPSUBN2	LFNG_HUMAN	Increases Expression	[6]
Osteoclast-stimulating factor 1 (OSTF1)	OT8D7CDO	OSTF1_HUMAN	Increases Expression	[6]
Caveolae-associated protein 3 (CAVIN3)	OTOLBK79	CAVN3_HUMAN	Increases Expression	[6]
Sorting nexin-21 (SNX21)	OT8O6909	SNX21_HUMAN	Increases Expression	[6]
Arrestin domain-containing protein 3 (ARRDC3)	OTAKW7R9	ARRD3_HUMAN	Increases Expression	[6]
Splicing factor ESS-2 homolog (ESS2)	OTZ08VCZ	ESS2_HUMAN	Increases Expression	[6]
Bcl-2-binding component 3, isoforms 3/4 (BBC3)	OTUAXDAY	BBC3B_HUMAN	Increases Expression	[6]
Sodium-coupled neutral amino acid symporter 2 (SLC38A2)	OTALABSK	S38A2_HUMAN	Increases Expression	[6]
Mediator of RNA polymerase II transcription subunit 15 (MED15)	OT0D0JVD	MED15_HUMAN	Increases Expression	[6]
Pleckstrin homology domain-containing family F member 1 (PLEKHF1)	OT9OL16U	PKHF1_HUMAN	Increases Expression	[6]
Sialidase-1 (NEU1)	OTH9BY8Y	NEUR1_HUMAN	Increases Expression	[6]
Translin-associated protein X (TSNAX)	OTZ9SGWB	TSNAX_HUMAN	Decreases Expression	[6]
Copine-1 (CPNE1)	OTH5YKSL	CPNE1_HUMAN	Decreases Expression	[6]
Allograft inflammatory factor 1-like (AIF1L)	OTDEOB80	AIF1L_HUMAN	Decreases Expression	[6]
Ferroptosis suppressor protein 1 (AIFM2)	OT57XWXO	FSP1_HUMAN	Increases Expression	[6]
Transmembrane emp24 domain-containing protein 9 (TMED9)	OTYGAQS0	TMED9_HUMAN	Decreases Expression	[6]
E3 ubiquitin-protein ligase RNF26 (RNF26)	OTPXA60S	RNF26_HUMAN	Decreases Expression	[6]
Tripartite motif-containing protein 2 (TRIM2)	OT0V1YVC	TRIM2_HUMAN	Increases Expression	[6]
Sorting nexin-25 (SNX25)	OT8JY8M1	SNX25_HUMAN	Increases Expression	[6]
tRNA dimethylallyltransferase (TRIT1)	OTCU9FS5	MOD5_HUMAN	Decreases Expression	[6]
PDZ and LIM domain protein 7 (PDLIM7)	OTAZVODU	PDLI7_HUMAN	Increases Expression	[6]
Phosphatidylinositol polyphosphate 5-phosphatase type IV (INPP5E)	OTJF2AZ9	INP5E_HUMAN	Increases Expression	[6]
Transmembrane protein 39A (TMEM39A)	OTRT51D9	TM39A_HUMAN	Increases Expression	[6]
Arginine and glutamate-rich protein 1 (ARGLU1)	OTRVRZ4Z	ARGL1_HUMAN	Increases Expression	[6]
SUN domain-containing protein 2 (SUN2)	OT2IQJUC	SUN2_HUMAN	Decreases Expression	[6]
B-cell receptor-associated protein 29 (BCAP29)	OTLUBG86	BAP29_HUMAN	Increases Expression	[6]
Proton-coupled zinc antiporter SLC30A1 (SLC30A1)	OTY8J0S4	ZNT1_HUMAN	Increases Expression	[6]
Solute carrier family 22 member 2 (SLC22A2)	OTGFK1AL	S22A2_HUMAN	Decreases Activity	[12]
Solute carrier family 22 member 1 (SLC22A1)	OT7817I4	S22A1_HUMAN	Decreases Activity	[12]
Solute carrier family 22 member 6 (SLC22A6)	OTKRCBVM	S22A6_HUMAN	Decreases Activity	[12]
Organic anion transporter 7 (SLC22A9)	OTO4BJCC	S22A9_HUMAN	Decreases Activity	[12]
Solute carrier family 22 member 11 (SLC22A11)	OTAJLNJZ	S22AB_HUMAN	Decreases Activity	[12]
Solute carrier family 22 member 7 (SLC22A7)	OTKTNH1W	S22A7_HUMAN	Decreases Activity	[12]
Diamine acetyltransferase 1 (SAT1)	OT52AU22	SAT1_HUMAN	Increases Expression	[13]
Aldo-keto reductase family 1 member C3 (AKR1C3)	OTU2SXBA	AK1C3_HUMAN	Decreases Activity	[14]
Aldo-keto reductase family 1 member C2 (AKR1C2)	OTQ2XMO3	AK1C2_HUMAN	Decreases Activity	[14]
Aldo-keto reductase family 1 member C1 (AKR1C1)	OTQKR4CM	AK1C1_HUMAN	Decreases Activity	[14]
Ladinin-1 (LAD1)	OT6YGTVX	LAD1_HUMAN	Increases Expression	[15]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B)	OTA1CPBV	TR10B_HUMAN	Increases Expression	[16]
ATP-binding cassette sub-family C member 3 (ABCC3)	OTC3IJV4	MRP3_HUMAN	Increases Expression	[17]
Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1)	OTY9R6FZ	ERN1_HUMAN	Increases Expression	[18]
DNA fragmentation factor subunit beta (DFFB)	OTPBW5N5	DFFB_HUMAN	Affects Localization	[19]
Apoptosis-inducing factor 1, mitochondrial (AIFM1)	OTKPWB7Q	AIFM1_HUMAN	Affects Localization	[19]
Renin (REN)	OT52GZR2	RENI_HUMAN	Decreases Activity	[20]
Metalloproteinase inhibitor 1 (TIMP1)	OTOXC51H	TIMP1_HUMAN	Affects Expression	[21]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Increases Expression	[22]
Transforming growth factor beta-1 proprotein (TGFB1)	OTV5XHVH	TGFB1_HUMAN	Increases Expression	[23]
Ferritin heavy chain (FTH1)	OT6IFS0O	FRIH_HUMAN	Increases Expression	[8]
Retinoblastoma-associated protein (RB1)	OTQJUJMZ	RB_HUMAN	Decreases Expression	[24]
Protein disulfide-isomerase (P4HB)	OTTYNYPF	PDIA1_HUMAN	Decreases Expression	[18]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Activity	[25]
Transcription factor 4 (TCF4)	OTB9ASTK	ITF2_HUMAN	Decreases Activity	[26]
Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6)	OTAFHAVI	ATF6A_HUMAN	Increases Expression	[18]
Nuclear factor NF-kappa-B p105 subunit (NFKB1)	OTNRRD8I	NFKB1_HUMAN	Decreases Activity	[27]
Galanin peptides (GAL)	OTB3VPTO	GALA_HUMAN	Affects Expression	[21]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Increases Phosphorylation	[28]
Protein-lysine 6-oxidase (LOX)	OT1C2HIU	LYOX_HUMAN	Decreases Expression	[29]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Increases Phosphorylation	[28]
Protein PML (PML)	OT6SM2GD	PML_HUMAN	Increases Expression	[30]
Leukocyte elastase inhibitor (SERPINB1)	OT5RDUFO	ILEU_HUMAN	Increases Expression	[15]
Catenin beta-1 (CTNNB1)	OTZ932A3	CTNB1_HUMAN	Decreases Expression	[31]
DNA damage-inducible transcript 3 protein (DDIT3)	OTI8YKKE	DDIT3_HUMAN	Increases Expression	[32]
Breast cancer type 1 susceptibility protein (BRCA1)	OT5BN6VH	BRCA1_HUMAN	Decreases Expression	[30]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[15]
Tumor necrosis factor ligand superfamily member 10 (TNFSF10)	OT4PXBTA	TNF10_HUMAN	Increases Response To Substance	[33]
Microsomal triglyceride transfer protein large subunit (MTTP)	OTNUVSDT	MTP_HUMAN	Increases Expression	[18]
Nucleosome assembly protein 1-like 1 (NAP1L1)	OTI7WBZV	NP1L1_HUMAN	Decreases Expression	[15]
Heat shock factor protein 1 (HSF1)	OTYNJ4KP	HSF1_HUMAN	Increases Activity	[34]
Transcription factor E2F1 (E2F1)	OTLKYBBC	E2F1_HUMAN	Decreases Expression	[24]
Beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,6-N-acetylglucosaminyltransferase (GCNT1)	OTF6OC66	GCNT1_HUMAN	Increases Expression	[8]
Cytochrome P450 4A11 (CYP4A11)	OTPU5J0S	CP4AB_HUMAN	Affects Activity	[35]
Transcription factor p65 (RELA)	OTUJP9CN	TF65_HUMAN	Increases Expression	[30]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Expression	[36]
Acetyl-CoA carboxylase 1 (ACACA)	OT5CQPZY	ACACA_HUMAN	Increases Expression	[18]
Endonuclease G, mitochondrial (ENDOG)	OT5IM7B3	NUCG_HUMAN	Affects Localization	[19]
Homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 1 protein (HERPUD1)	OT9EROL6	HERP1_HUMAN	Increases Expression	[8]
Bcl-2 homologous antagonist/killer (BAK1)	OTDP6ILW	BAK_HUMAN	Affects Localization	[37]
Carbonic anhydrase 9 (CA9)	OTNA51XT	CAH9_HUMAN	Decreases Expression	[29]
Dehydrogenase/reductase SDR family member 11 (DHRS11)	OTU3J0ZL	DHR11_HUMAN	Decreases Activity	[38]
Protein NDRG1 (NDRG1)	OTVO66BO	NDRG1_HUMAN	Increases Expression	[30]
Bcl2-associated agonist of cell death (BAD)	OT63ERYM	BAD_HUMAN	Decreases Expression	[39]
Transmembrane 7 superfamily member 3 (TM7SF3)	OTT9RKL6	TM7S3_HUMAN	Decreases Expression	[8]
Eukaryotic translation initiation factor 2-alpha kinase 3 (EIF2AK3)	OT0DZGY4	E2AK3_HUMAN	Increases Expression	[18]
eIF5-mimic protein 1 (BZW2)	OTBT0A1B	5MP1_HUMAN	Decreases Expression	[8]
Flavin-containing monooxygenase 3 (FMO3)	OT1G2EV3	FMO3_HUMAN	Increases Metabolism	[40]

Indication(s) of Idarubicin

Disease Entry	ICD 11	Status	REF
Acute myelogenous leukaemia	2A41	Approved	[4]
Acute myeloid leukaemia	2A60	Approved	[5]
Adult acute monocytic leukemia	N.A.	Approved	[4]
Childhood acute megakaryoblastic leukemia	N.A.	Approved	[4]
Leukemia	N.A.	Approved	[4]

Idarubicin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
DNA topoisomerase II (TOP2)	TT0IHXV	TOP2A_HUMAN; TOP2B_HUMAN	Modulator	[42]

Idarubicin Interacts with 3 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 1 (ABCC1)	DTSYQGK	MRP1_HUMAN	Substrate	[43]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[44]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[44]

Idarubicin Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[45]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[45]

Idarubicin Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Natriuretic peptides B (NPPB)	OTSN2IPY	ANFB_HUMAN	Increases Expression	[46]
Bile acid receptor (NR1H4)	OTWZLPTB	NR1H4_HUMAN	Decreases Activity	[41]

References

• [1] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
• [2] Sulindac 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: 5425).
• [4] Idarubicin FDA Label
• [5] 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: 7083).
• [6] Expression profile analysis of colon cancer cells in response to sulindac or aspirin. Biochem Biophys Res Commun. 2002 Mar 29;292(2):498-512.
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• [8] Growth-suppressive effect of non-steroidal anti-inflammatory drugs on 11 colon-cancer cell lines and fluorescence differential display of genes whose expression is influenced by sulindac. Int J Cancer. 2000 Dec 15;88(6):873-80. doi: 10.1002/1097-0215(20001215)88:6<873::aid-ijc6>3.0.co;2-b.
• [9] Glucuronidation of nonsteroidal anti-inflammatory drugs: identifying the enzymes responsible in human liver microsomes. Drug Metab Dispos. 2005 Jul;33(7):1027-35.
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