Details of the Drug Combination

General Information of Drug Combination (ID: DCR0C3E)

• Drug Combination Name: Mestranol + Idarubicin
• Indication: Glioblastoma?; Status: Investigative [1]
• Component Drugs:
  Mestranol (DMG3F94): Small molecular drug
  Idarubicin (DMM0XGL): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: T98G
  Zero Interaction Potency (ZIP) Score: 19.98
  Bliss Independence Score: 19.98
  Loewe Additivity Score: 12.21
  LHighest Single Agent (HSA) Score: 12.21

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Mestranol

Disease Entry	ICD 11	Status	REF
Contraception	QA21	Approved	[2]
Menorrhagia	GA20.50	Approved	[3]
Endometriosis	GA10	Investigative	[3]

Mestranol Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Estrogen receptor (ESR)	TTZAYWL	ESR1_HUMAN	Agonist	[7]

Mestranol Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[8]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[9]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[10]

Mestranol Interacts with 30 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
E3 ubiquitin-protein ligase SIAH2 (SIAH2)	OTKED2XN	SIAH2_HUMAN	Increases Expression	[6]
Carbonic anhydrase 12 (CA12)	OT6WNFU8	CAH12_HUMAN	Increases Expression	[6]
Tyrosine-protein kinase JAK2 (JAK2)	OTBIDOOR	JAK2_HUMAN	Increases Expression	[6]
monooxygenase MICAL2 (MICAL2)	OT04OQQJ	MICA2_HUMAN	Increases Expression	[6]
Serine protease 23 (PRSS23)	OT6DQAM1	PRS23_HUMAN	Increases Expression	[6]
Supervillin (SVIL)	OTWQQ1WK	SVIL_HUMAN	Increases Expression	[6]
Transcription factor AP-2-alpha (TFAP2A)	OTMYT3NK	AP2A_HUMAN	Decreases Expression	[6]
Monoacylglycerol lipase ABHD2 (ABHD2)	OTCRUOCS	ABHD2_HUMAN	Increases Expression	[6]
Transcriptional activator Myb (MYB)	OTJH64IV	MYB_HUMAN	Increases Expression	[6]
Myb-related protein A (MYBL1)	OTBJMC2P	MYBA_HUMAN	Increases Expression	[6]
CD44 antigen (CD44)	OT9TTJ41	CD44_HUMAN	Increases Expression	[6]
Ephrin-A1 (EFNA1)	OTU2NUA2	EFNA1_HUMAN	Decreases Expression	[6]
Single-stranded DNA-binding protein 2 (SSBP2)	OTYG1G80	SSBP2_HUMAN	Decreases Expression	[6]
Large neutral amino acids transporter small subunit 1 (SLC7A5)	OT2WPVXD	LAT1_HUMAN	Increases Expression	[6]
DNA-binding protein inhibitor ID-3 (ID3)	OTUULW5Z	ID3_HUMAN	Decreases Expression	[6]
Early growth response protein 3 (EGR3)	OTGPJIRA	EGR3_HUMAN	Increases Expression	[6]
Four and a half LIM domains protein 2 (FHL2)	OT0OAYWT	FHL2_HUMAN	Increases Expression	[6]
Cyclin-G2 (CCNG2)	OTII38K2	CCNG2_HUMAN	Decreases Expression	[6]
Na(+)/H(+) exchange regulatory cofactor NHE-RF3 (PDZK1)	OTGFK4MH	NHRF3_HUMAN	Increases Expression	[6]
Phosphatidylinositol 3-kinase regulatory subunit gamma (PIK3R3)	OTXGJ8N1	P55G_HUMAN	Decreases Expression	[6]
Transcription factor AP-2 gamma (TFAP2C)	OTUDIW05	AP2C_HUMAN	Increases Expression	[6]
Serine/threonine-protein kinase Sgk3 (SGK3)	OTQ6QO99	SGK3_HUMAN	Increases Expression	[6]
Inactive rhomboid protein 1 (RHBDF1)	OTCQ7UDS	RHDF1_HUMAN	Decreases Expression	[6]
Calmin (CLMN)	OT7U5J3T	CLMN_HUMAN	Decreases Expression	[6]
DNA endonuclease RBBP8 (RBBP8)	OTRHJ3GI	CTIP_HUMAN	Increases Expression	[6]
Noelin (OLFM1)	OTOYPEWW	NOE1_HUMAN	Increases Expression	[6]
Pleckstrin homology domain-containing family F member 2 (PLEKHF2)	OTBGDG8C	PKHF2_HUMAN	Decreases Expression	[6]
Rap guanine nucleotide exchange factor-like 1 (RAPGEFL1)	OTYKE9ZM	RPGFL_HUMAN	Increases Expression	[6]
RNA 3'-terminal phosphate cyclase-like protein (RCL1)	OT7O00YX	RCL1_HUMAN	Increases Expression	[6]
Protein GREB1 (GREB1)	OTU6ZA26	GREB1_HUMAN	Increases Expression	[11]

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	[13]

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	[14]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[15]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[15]

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	[16]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[16]

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	[17]
Bile acid receptor (NR1H4)	OTWZLPTB	NR1H4_HUMAN	Decreases Activity	[12]

References

• [1] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
• [2] 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: 7087).
• [3] Mestranol FDA Label
• [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] Moving toward integrating gene expression profiling into high-throughput testing: a gene expression biomarker accurately predicts estrogen receptor alpha modulation in a microarray compendium. Toxicol Sci. 2016 May;151(1):88-103.
• [7] Short-term effects of environmentally relevant concentrations of EDC mixtures on Mytilus galloprovincialis digestive gland. Aquat Toxicol. 2008 May 30;87(4):272-9.
• [8] Prescribrt's digital referenve - Ethinyl estradiol/norethindrone; mestranol/norethindrone - Drug Summary
• [9] Loss of orally administered drugs in GI tract. Saudi Pharm J. 2012 Oct;20(4):331-44.
• [10] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
• [11] A Gene Expression Biomarker Identifies Chemical Modulators of Estrogen Receptor in an MCF-7 Microarray Compendium. Chem Res Toxicol. 2021 Feb 15;34(2):313-329. doi: 10.1021/acs.chemrestox.0c00243. Epub 2021 Jan 6.
• [12] 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.
• [13] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [14] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [15] Amonafide L-malate is not a substrate for multidrug resistance proteins in secondary acute myeloid leukemia. Leukemia. 2008 Nov;22(11):2110-5.
• [16] In vitro evaluation of cytochrome P450-mediated drug interactions between cytarabine, idarubicin, itraconazole and caspofungin. Hematology. 2004 Jun;9(3):217-21.
• [17] The use of biochemical markers in cardiotoxicity monitoring in patients treated for leukemia. Neoplasma. 2005;52(5):430-4.