Details of the Drug Combination

General Information of Drug Combination (ID: DCUX4SM)

• Drug Combination Name: Prednisolone + Idarubicin
• Indication: Glioblastoma?; Status: Investigative [1]
• Component Drugs:
  Prednisolone (DMQ8FR2): Small molecular drug
  Idarubicin (DMM0XGL): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: T98G
  Zero Interaction Potency (ZIP) Score: 11.03
  Bliss Independence Score: 11.03
  Loewe Additivity Score: 13.73
  LHighest Single Agent (HSA) Score: 13.73

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Prednisolone

Disease Entry	ICD 11	Status	REF
Acute adrenal insufficiency	N.A.	Approved	[2]
Acute asthma	CA23	Approved	[2]
Addison disease	5A74.0	Approved	[2]
Allergic rhinitis	CA08.0	Approved	[2]
Angioedema	4A00.15	Approved	[2]
Aspiration pneumonitis	N.A.	Approved	[2]
Autoimmune haemolytic anaemia	3A20	Approved	[2]
Blepharoconjunctivitis	N.A.	Approved	[2]
Bursitis	N.A.	Approved	[2]
Cerebral edema	8D60.1	Approved	[2]
Chronic graft versus host disease	N.A.	Approved	[2]
Congenital adrenal hyperplasia	5A71.01	Approved	[2]
Corneal abrasion	NA06.4	Approved	[2]
Corneal ulcer	9A76	Approved	[2]
Crohn disease	DD70	Approved	[2]
Dacryocystitis	N.A.	Approved	[2]
Demodex blepharitis	1G07	Approved	[2]
Dermatitis herpetiformis	EB44	Approved	[2]
Diamond-Blackfan anemia	N.A.	Approved	[2]
Disorder of orbital region	N.A.	Approved	[2]
Epicondylitis	N.A.	Approved	[2]
Erythema multiforme	N.A.	Approved	[2]
Exanthem	N.A.	Approved	[2]
Fever	MG26	Approved	[2]
Granuloma annulare	N.A.	Approved	[2]
Hypersensitivity pneumonitis	N.A.	Approved	[2]
Inflammatory bowel disease	DD72	Approved	[2]
Ischemia-reperfusion injury	DB98.B	Approved	[2]
Keratitis	N.A.	Approved	[2]
Leukemia	N.A.	Approved	[2]
Lupus nephritis	4A40.0Y	Approved	[2]
Microscopic polyangiitis	N.A.	Approved	[2]
Miliary tuberculosis	N.A.	Approved	[2]
Mycosis fungoides	2B01	Approved	[2]
Myeloproliferative neoplasm	2A20	Approved	[2]
Pneumocystis pneumonia	CA40.20	Approved	[2]
Polymyalgia rheumatica	N.A.	Approved	[2]
Primary cutaneous T-cell lymphoma	N.A.	Approved	[2]
Psoriasis	EA90	Approved	[2]
Psoriatic arthritis	FA21	Approved	[2]
Rheumatic heart disease	N.A.	Approved	[2]
Rosacea	ED90.0	Approved	[2]
Sarcoidosis	4B20.5	Approved	[2]
Serum sickness	N.A.	Approved	[2]
Severe asthma	CA23	Approved	[2]
Skin disease	EA00-EM0Z	Approved	[2]
Solid tumour/cancer	2A00-2F9Z	Approved	[3]
Sympathetic ophthalmia	N.A.	Approved	[2]
Systemic lupus erythematosus	4A40.0	Approved	[2]
Ulcerative colitis	DD71	Approved	[2]
Multiple sclerosis	8A40	Phase 3	[4]
Acquired thrombocytopenia	N.A.	Investigative	[2]
Asthma	CA23	Investigative	[2]
Beta-thalassemia major	N.A.	Investigative	[2]
Classic Hodgkin lymphoma	N.A.	Investigative	[2]
Follicular lymphoma	2A80	Investigative	[2]
Iridocyclitis	N.A.	Investigative	[2]
Sjogren syndrome	4A43.20	Investigative	[2]
Synovitis	N.A.	Investigative	[2]
Uveitis	9A96.Z	Investigative	[2]

Prednisolone Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Glucocorticoid receptor (NR3C1)	TTYRL6O	GCR_HUMAN	Modulator	[10]

Prednisolone Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[11]

Prednisolone Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[12]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[13]

Prednisolone Interacts with 89 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
CCN family member 1 (CCN1)	OTKJBEMD	CCN1_HUMAN	Increases Expression	[7]
Phospholipid phosphatase 3 (PLPP3)	OTSSF7BK	PLPP3_HUMAN	Decreases Expression	[7]
Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3)	OTPGHZB9	IFIT3_HUMAN	Decreases Expression	[7]
Calmegin (CLGN)	OTEWVFQV	CLGN_HUMAN	Decreases Expression	[7]
Receptor-interacting serine/threonine-protein kinase 2 (RIPK2)	OT0KMIYQ	RIPK2_HUMAN	Decreases Expression	[7]
Gasdermin-E (GSDME)	OT1ZWY32	GSDME_HUMAN	Decreases Expression	[7]
CCN family member 5 (CCN5)	OTADU8JJ	CCN5_HUMAN	Increases Expression	[7]
Antiviral innate immune response receptor RIG-I (RIGI)	OTFIIC43	RIGI_HUMAN	Decreases Expression	[7]
2'-5'-oligoadenylate synthase 1 (OAS1)	OT8ZLOCY	OAS1_HUMAN	Decreases Expression	[7]
Collagen alpha-1(I) chain (COL1A1)	OTI31178	CO1A1_HUMAN	Increases Expression	[7]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Decreases Expression	[7]
Ubiquitin-like protein ISG15 (ISG15)	OT53QQ7N	ISG15_HUMAN	Decreases Expression	[7]
Hepatocyte growth factor receptor (MET)	OT7K55MU	MET_HUMAN	Decreases Expression	[7]
Neuromedin-B (NMB)	OT4NLN6H	NMB_HUMAN	Decreases Expression	[7]
Stromelysin-2 (MMP10)	OTJDWW8Q	MMP10_HUMAN	Decreases Expression	[7]
Growth-regulated alpha protein (CXCL1)	OT3WCTZV	GROA_HUMAN	Decreases Expression	[7]
Interferon alpha-inducible protein 6 (IFI6)	OTWOOAM4	IFI6_HUMAN	Decreases Expression	[7]
Interferon-induced protein with tetratricopeptide repeats 1 (IFIT1)	OTXOQDSG	IFIT1_HUMAN	Decreases Expression	[7]
C-X-C motif chemokine 3 (CXCL3)	OTSL94KH	CXCL3_HUMAN	Decreases Expression	[7]
Interferon-induced GTP-binding protein Mx1 (MX1)	OT6X8G5T	MX1_HUMAN	Decreases Expression	[7]
Fibulin-1 (FBLN1)	OT5MHHOP	FBLN1_HUMAN	Increases Expression	[7]
Atypical chemokine receptor 3 (ACKR3)	OTA6GA4F	ACKR3_HUMAN	Decreases Expression	[7]
Adenosine receptor A2a (ADORA2A)	OTVRBZ0I	AA2AR_HUMAN	Decreases Expression	[7]
CCN family member 2 (CCN2)	OTC39NSU	CCN2_HUMAN	Increases Expression	[7]
Guanylate-binding protein 1 (GBP1)	OTUM7RPJ	GBP1_HUMAN	Decreases Expression	[7]
Macrophage metalloelastase (MMP12)	OT9Z7LHM	MMP12_HUMAN	Decreases Expression	[7]
Interferon alpha-inducible protein 27, mitochondrial (IFI27)	OTI2XGIT	IFI27_HUMAN	Decreases Expression	[7]
Prolargin (PRELP)	OT9EEBUJ	PRELP_HUMAN	Increases Expression	[7]
Spermine synthase (SMS)	OT8JYKNH	SPSY_HUMAN	Decreases Expression	[7]
C-C motif chemokine 20 (CCL20)	OTUCJY4N	CCL20_HUMAN	Decreases Expression	[7]
DNA-binding protein inhibitor ID-3 (ID3)	OTUULW5Z	ID3_HUMAN	Increases Expression	[7]
Tumor necrosis factor alpha-induced protein 2 (TNFAIP2)	OTRZH80H	TNAP2_HUMAN	Decreases Expression	[7]
EGF-containing fibulin-like extracellular matrix protein 1 (EFEMP1)	OTZVUOOB	FBLN3_HUMAN	Increases Expression	[7]
Neuronal membrane glycoprotein M6-b (GPM6B)	OT8Q1582	GPM6B_HUMAN	Increases Expression	[7]
Laminin subunit beta-3 (LAMB3)	OTFPU6W8	LAMB3_HUMAN	Decreases Expression	[7]
Nidogen-2 (NID2)	OTHC33FF	NID2_HUMAN	Increases Expression	[7]
Signal transducer and activator of transcription 4 (STAT4)	OTAK3VFR	STAT4_HUMAN	Decreases Expression	[7]
2'-5'-oligoadenylate synthase-like protein (OASL)	OTZ05YRP	OASL_HUMAN	Decreases Expression	[7]
Lymphocyte antigen 6E (LY6E)	OTMG16BZ	LY6E_HUMAN	Decreases Expression	[7]
Interferon-induced protein 44-like (IFI44L)	OTXKORJP	IF44L_HUMAN	Decreases Expression	[7]
Olfactomedin-like protein 2B (OLFML2B)	OTDNJFR4	OLM2B_HUMAN	Increases Expression	[7]
E3 ubiquitin-protein ligase RNF19B (RNF19B)	OTYCWKBP	RN19B_HUMAN	Decreases Expression	[7]
Amphoterin-induced protein 2 (AMIGO2)	OTPAIT1O	AMGO2_HUMAN	Decreases Expression	[7]
Probable E3 ubiquitin-protein ligase HERC6 (HERC6)	OT7G9PQE	HERC6_HUMAN	Decreases Expression	[7]
Equilibrative nucleobase transporter 1 (SLC43A3)	OTR60ZLA	S43A3_HUMAN	Decreases Expression	[7]
Interferon-induced protein 44 (IFI44)	OTOKSZVA	IFI44_HUMAN	Decreases Expression	[7]
S-adenosylmethionine-dependent nucleotide dehydratase RSAD2 (RSAD2)	OTCA9WCM	RSAD2_HUMAN	Decreases Expression	[7]
Nuclear receptor subfamily 4 group A member 3 (NR4A3)	OTPBE9R1	NR4A3_HUMAN	Decreases Expression	[7]
Type II iodothyronine deiodinase (DIO2)	OTGPNSLH	IOD2_HUMAN	Increases Expression	[7]
Interferon regulatory factor 7 (IRF7)	OTC1A2PQ	IRF7_HUMAN	Decreases Expression	[7]
Interferon-stimulated gene 20 kDa protein (ISG20)	OTCWRJJW	ISG20_HUMAN	Decreases Expression	[7]
Interferon-induced helicase C domain-containing protein 1 (IFIH1)	OTZA2AHA	IFIH1_HUMAN	Decreases Expression	[7]
Anthrax toxin receptor 1 (ANTXR1)	OT5W1GPC	ANTR1_HUMAN	Increases Expression	[7]
Interleukin-23 subunit alpha (IL23A)	OTYO99HC	IL23A_HUMAN	Decreases Expression	[7]
NADH dehydrogenase 1 alpha subcomplex subunit 4-like 2 (NDUFA4L2)	OTK0PG7R	NUA4L_HUMAN	Decreases Expression	[7]
Large neutral amino acids transporter small subunit 2 (SLC7A8)	OT8XXVO8	LAT2_HUMAN	Increases Expression	[7]
E3 ISG15--protein ligase HERC5 (HERC5)	OTZ5PR39	HERC5_HUMAN	Decreases Expression	[7]
Paired immunoglobulin-like type 2 receptor alpha (PILRA)	OTBE0PLF	PILRA_HUMAN	Decreases Expression	[7]
Hydroxymethylglutaryl-CoA synthase, cytoplasmic (HMGCS1)	OTCO26FV	HMCS1_HUMAN	Increases Expression	[8]
Inactive phospholipase C-like protein 1 (PLCL1)	OTJL2C79	PLCL1_HUMAN	Increases Expression	[8]
Cyclin-G2 (CCNG2)	OTII38K2	CCNG2_HUMAN	Increases Expression	[8]
Programmed cell death protein 4 (PDCD4)	OTZ6NXUX	PDCD4_HUMAN	Increases Expression	[8]
Kelch-like protein 24 (KLHL24)	OTWZSX5C	KLH24_HUMAN	Increases Expression	[8]
Protein FAM200C (FAM200C)	OTZOXUEK	F200C_HUMAN	Increases Expression	[8]
Arrestin domain-containing protein 3 (ARRDC3)	OTAKW7R9	ARRD3_HUMAN	Increases Expression	[8]
Sulfiredoxin-1 (SRXN1)	OTYDBO4L	SRXN1_HUMAN	Increases Expression	[8]
Cysteine-rich motor neuron 1 protein (CRIM1)	OTTZNV6Y	CRIM1_HUMAN	Increases Expression	[8]
SLAM family member 5 (CD84)	OTAY5B0F	SLAF5_HUMAN	Increases Expression	[8]
PDZ and LIM domain protein 1 (PDLIM1)	OT4EGCPG	PDLI1_HUMAN	Increases Expression	[14]
Basic helix-loop-helix ARNT-like protein 1 (BMAL1)	OTMI12L2	BMAL1_HUMAN	Increases Expression	[15]
Period circadian protein homolog 2 (PER2)	OTU2B1DJ	PER2_HUMAN	Decreases Expression	[15]
Period circadian protein homolog 1 (PER1)	OTVQF3WX	PER1_HUMAN	Increases Expression	[15]
Transforming growth factor beta-1 proprotein (TGFB1)	OTV5XHVH	TGFB1_HUMAN	Decreases Expression	[16]
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Increases Expression	[17]
Serotransferrin (TF)	OT41PEMS	TRFE_HUMAN	Increases Expression	[17]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Decreases Expression	[14]
C-C motif chemokine 3 (CCL3)	OTW2H3ND	CCL3_HUMAN	Increases Expression	[9]
C-C motif chemokine 4 (CCL4)	OT6B8P25	CCL4_HUMAN	Increases Expression	[9]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Decreases Expression	[9]
Nuclear receptor subfamily 1 group D member 1 (NR1D1)	OTJ38PTB	NR1D1_HUMAN	Decreases Expression	[15]
Long-chain-fatty-acid--CoA ligase 1 (ACSL1)	OTB06ESI	ACSL1_HUMAN	Increases Expression	[14]
Tissue factor pathway inhibitor 2 (TFPI2)	OTZCRWOR	TFPI2_HUMAN	Decreases Expression	[14]
Transcription factor SOX-9 (SOX9)	OTVDJFGN	SOX9_HUMAN	Decreases Expression	[14]
D site-binding protein (DBP)	OTE0W7LN	DBP_HUMAN	Decreases Expression	[15]
Cryptochrome-1 (CRY1)	OTTGAJT0	CRY1_HUMAN	Decreases Expression	[15]
Mucin-16 (MUC16)	OTHPPE67	MUC16_HUMAN	Decreases Expression	[18]
Histone-lysine N-methyltransferase 2A (KMT2A)	OT9GLJI6	KMT2A_HUMAN	Decreases Response To Substance	[19]
Mothers against decapentaplegic homolog 1 (SMAD1)	OTQSHR25	SMAD1_HUMAN	Increases ADR	[20]
Catenin beta-1 (CTNNB1)	OTZ932A3	CTNB1_HUMAN	Increases ADR	[20]

Indication(s) of Idarubicin

Disease Entry	ICD 11	Status	REF
Acute myelogenous leukaemia	2A41	Approved	[5]
Acute myeloid leukaemia	2A60	Approved	[6]
Adult acute monocytic leukemia	N.A.	Approved	[5]
Childhood acute megakaryoblastic leukemia	N.A.	Approved	[5]
Leukemia	N.A.	Approved	[5]

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	[22]

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	[23]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[24]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[24]

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	[25]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[25]

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	[26]
Bile acid receptor (NR1H4)	OTWZLPTB	NR1H4_HUMAN	Decreases Activity	[21]

References

• [1] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
• [2] Prednisolone FDA Label
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [4] 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: 2866).
• [5] Idarubicin 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: 7083).
• [7] Antirheumatic drug response signatures in human chondrocytes: potential molecular targets to stimulate cartilage regeneration. Arthritis Res Ther. 2009;11(1):R15.
• [8] Transcriptome-based functional classifiers for direct immunotoxicity. Arch Toxicol. 2014 Mar;88(3):673-89.
• [9] Cell-based and cytokine-directed chemical screen to identify potential anti-multiple myeloma agents. Leuk Res. 2010 Jul;34(7):917-24. doi: 10.1016/j.leukres.2009.12.002. Epub 2010 Feb 8.
• [10] Aldosterone (mineralocorticoid) equivalent to prednisolone (glucocorticoid) in reversing hearing loss in MRL/MpJ-Fas1pr autoimmune mice. Laryngoscope. 2000 Nov;110(11):1902-6.
• [11] The role of the efflux transporter P-glycoprotein in brain penetration of prednisolone. J Endocrinol. 2002 Oct;175(1):251-60.
• [12] Inter-individual difference determinant of prednisolone pharmacokinetics for Japanese renal transplant recipients in the maintenance stage. Xenobiotica. 2009 Dec;39(12):939-45.
• [13] Pharmacokinetic and pharmacoimmunodynamic interactions between prednisolone and sirolimus in adrenalectomized rats. J Pharmacokinet Biopharm. 1999 Feb;27(1):1-21.
• [14] Gene expression profiling of rheumatoid arthritis synovial cells treated with antirheumatic drugs. J Biomol Screen. 2007 Apr;12(3):328-40. doi: 10.1177/1087057107299261. Epub 2007 Mar 22.
• [15] Chronic treatment with prednisolone represses the circadian oscillation of clock gene expression in mouse peripheral tissues. Mol Endocrinol. 2006 Mar;20(3):573-83. doi: 10.1210/me.2005-0165. Epub 2005 Nov 3.
• [16] Steroid therapy and urinary transforming growth factor-beta1 in IgA nephropathy. Am J Kidney Dis. 2001 Dec;38(6):1191-8. doi: 10.1053/ajkd.2001.29209.
• [17] Prednisolone can increase glomerular permeability to proteins in nephrotic syndrome. Kidney Int. 1988 Jun;33(6):1169-74. doi: 10.1038/ki.1988.126.
• [18] Dermatomyositis associated with membranous nephropathy in a 43-year-old female. Am J Nephrol. 2002 Jul-Aug;22(4):385-8. doi: 10.1159/000065233.
• [19] In vitro drug-resistance profile in infant acute lymphoblastic leukemia in relation to age, MLL rearrangements and immunophenotype. Leukemia. 2004 Mar;18(3):521-9. doi: 10.1038/sj.leu.2403253.
• [20] 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.
• [21] Quantitative high-throughput profiling of environmental chemicals and drugs that modulate farnesoid X receptor. Sci Rep. 2014 Sep 26;4:6437. doi: 10.1038/srep06437.
• [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] Amonafide L-malate is not a substrate for multidrug resistance proteins in secondary acute myeloid leukemia. Leukemia. 2008 Nov;22(11):2110-5.
• [25] In vitro evaluation of cytochrome P450-mediated drug interactions between cytarabine, idarubicin, itraconazole and caspofungin. Hematology. 2004 Jun;9(3):217-21.
• [26] The use of biochemical markers in cardiotoxicity monitoring in patients treated for leukemia. Neoplasma. 2005;52(5):430-4.