Details of the Drug Combination

General Information of Drug Combination (ID: DCJ2QNF)

• Drug Combination Name: Oxamflatin + Idarubicin
• Indication: Glioblastoma?; Status: Investigative [1]
• Component Drugs:
  Oxamflatin (DM1TG3C): Small molecular drug
  Idarubicin (DMM0XGL): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: T98G
  Zero Interaction Potency (ZIP) Score: 13.21
  Bliss Independence Score: 13.21
  Loewe Additivity Score: 23.6
  LHighest Single Agent (HSA) Score: 23.64

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Oxamflatin

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Terminated	[2]

Oxamflatin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Histone deacetylase 1 (HDAC1)	TT6R7JZ	HDAC1_HUMAN	Inhibitor	[6]

Oxamflatin Interacts with 15 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Transcription factor E2F8 (E2F8)	OTQKZGFP	E2F8_HUMAN	Decreases Expression	[7]
Dual specificity tyrosine-phosphorylation-regulated kinase 3 (DYRK3)	OTX1C2GS	DYRK3_HUMAN	Increases Expression	[7]
Transmembrane and coiled-coil domains protein 2 (TMCC2)	OT0D7IYD	TMCC2_HUMAN	Increases Expression	[7]
Max-interacting protein 1 (MXI1)	OTUQ9E0D	MXI1_HUMAN	Increases Expression	[7]
Enhancer of filamentation 1 (NEDD9)	OTGCFN4M	CASL_HUMAN	Increases Expression	[7]
Cytoplasmic polyadenylation element-binding protein 4 (CPEB4)	OTW1SCZW	CPEB4_HUMAN	Increases Expression	[7]
Transforming growth factor beta activator LRRC33 (NRROS)	OT9WNOKY	LRC33_HUMAN	Decreases Expression	[7]
TBC1 domain family member 16 (TBC1D16)	OTPR3C6A	TBC16_HUMAN	Increases Expression	[7]
ELL-associated factor 2 (EAF2)	OTSOET5L	EAF2_HUMAN	Increases Expression	[7]
Pre-mRNA-splicing factor RBM22 (RBM22)	OTFW0IGK	RBM22_HUMAN	Decreases Expression	[7]
PH and SEC7 domain-containing protein 3 (PSD3)	OTTN9B9O	PSD3_HUMAN	Increases Expression	[7]
Tropomodulin-2 (TMOD2)	OTTTUH2W	TMOD2_HUMAN	Increases Expression	[7]
Solute carrier family 12 member 6 (SLC12A6)	OT9CS413	S12A6_HUMAN	Increases Expression	[7]
RING finger protein 24 (RNF24)	OTUZI597	RNF24_HUMAN	Increases Expression	[7]
DmX-like protein 1 (DMXL1)	OTWVL31L	DMXL1_HUMAN	Increases Expression	[7]

Indication(s) of Idarubicin

Disease Entry	ICD 11	Status	REF
Acute myelogenous leukaemia	2A41	Approved	[3]
Acute myeloid leukaemia	2A60	Approved	[4]
Adult acute monocytic leukemia	N.A.	Approved	[3]
Childhood acute megakaryoblastic leukemia	N.A.	Approved	[3]
Leukemia	N.A.	Approved	[3]

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	[9]

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	[10]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[11]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[11]

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	[12]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[12]

Idarubicin Interacts with 9 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Estrogen receptor (ESR1)	OTKLU61J	ESR1_HUMAN	Decreases Activity	[8]
Heme oxygenase 1 (HMOX1)	OTC1W6UX	HMOX1_HUMAN	Increases Expression	[13]
Androgen receptor (AR)	OTUBKAZZ	ANDR_HUMAN	Increases Activity	[8]
Natriuretic peptides B (NPPB)	OTSN2IPY	ANFB_HUMAN	Increases Expression	[14]
Peroxisome proliferator-activated receptor gamma (PPARG)	OTHMARHO	PPARG_HUMAN	Decreases Activity	[8]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[15]
Peroxisome proliferator-activated receptor delta (PPARD)	OTI4WTOP	PPARD_HUMAN	Decreases Activity	[8]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Decreases Activity	[16]
Bile acid receptor (NR1H4)	OTWZLPTB	NR1H4_HUMAN	Decreases Activity	[8]

References

• [1] Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
• [2] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007547)
• [3] Idarubicin FDA Label
• [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: 7083).
• [5] Histone deacetylase inhibitor enhances 5-fluorouracil cytotoxicity by down-regulating thymidylate synthase in human cancer cells. Mol Cancer Ther. 2006 Dec;5(12):3085-95.
• [6] Histone deacetylase inhibitors in cancer therapy: latest developments, trends and medicinal chemistry perspective. Anticancer Agents Med Chem. 2007 Sep;7(5):576-92.
• [7] Development and validation of the TGx-HDACi transcriptomic biomarker to detect histone deacetylase inhibitors in human TK6 cells. Arch Toxicol. 2021 May;95(5):1631-1645. doi: 10.1007/s00204-021-03014-2. Epub 2021 Mar 26.
• [8] 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.
• [9] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [10] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [11] Amonafide L-malate is not a substrate for multidrug resistance proteins in secondary acute myeloid leukemia. Leukemia. 2008 Nov;22(11):2110-5.
• [12] In vitro evaluation of cytochrome P450-mediated drug interactions between cytarabine, idarubicin, itraconazole and caspofungin. Hematology. 2004 Jun;9(3):217-21.
• [13] A Quantitative Approach to Screen for Nephrotoxic Compounds In Vitro. J Am Soc Nephrol. 2016 Apr;27(4):1015-28. doi: 10.1681/ASN.2015010060. Epub 2015 Aug 10.
• [14] The use of biochemical markers in cardiotoxicity monitoring in patients treated for leukemia. Neoplasma. 2005;52(5):430-4.
• [15] The induction of apoptosis by daunorubicin and idarubicin in human trisomic and diabetic fibroblasts. Cell Mol Biol Lett. 2008;13(2):182-94. doi: 10.2478/s11658-007-0045-7. Epub 2008 Apr 10.
• [16] Refining the human iPSC-cardiomyocyte arrhythmic risk assessment model. Toxicol Sci. 2013 Dec;136(2):581-94. doi: 10.1093/toxsci/kft205. Epub 2013 Sep 19.