Details of the Drug Combination

General Information of Drug Combination (ID: DCNX1FO)

Drug Combination Name

Ospemifene DZNep

Indication

Disease Entry	Status	REF
Lymphoid neoplasm	Investigative	[1]

Component Drugs

Ospemifene DMC4GEI

DZNep DM0JXBK

Small molecular drug

2D MOL

3D MOL

3D MOL is unavailable

High-throughput Screening Result

Testing Cell Line: Mak

Zero Interaction Potency (ZIP) Score: 9.103

Bliss Independence Score: 6.609

Loewe Additivity Score: 9.903

LHighest Single Agent (HSA) Score: 12.524

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)

Indication(s) of Ospemifene

Disease Entry	ICD 11	Status	REF
Dyspareunia	GA12	Approved	[2]
Postmenopausal vaginal atrophy	GA30.2	Phase 3	[2]

Ospemifene Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Estrogen receptor (ESR)	TTZAYWL	ESR1_HUMAN	Modulator	[4]
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Ospemifene Interacts with 4 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[5]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[5]
Cytochrome P450 2B6 (CYP2B6)	DEPKLMQ	CP2B6_HUMAN	Metabolism	[5]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[5]
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Ospemifene Interacts with 3 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Estrogen receptor (ESR1)	OTKLU61J	ESR1_HUMAN	Decreases Expression	[6]
Trefoil factor 1 (TFF1)	OTCYQH4F	TFF1_HUMAN	Decreases Expression	[6]
Androgen receptor (AR)	OTUBKAZZ	ANDR_HUMAN	Decreases Expression	[6]
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Indication(s) of DZNep

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[3]

DZNep Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Adenosylhomocysteinase (AHCY)	TTE2KUJ	SAHH_HUMAN	Inhibitor	[3]
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DZNep Interacts with 24 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Huntingtin-interacting protein 1 (HIP1)	OT7AKCFQ	HIP1_HUMAN	Decreases Expression	[7]
Histone-lysine N-methyltransferase SUV39H1 (SUV39H1)	OTDTF5BU	SUV91_HUMAN	Increases Expression	[7]
Histone-lysine N-methyltransferase NSD2 (NSD2)	OTQ6SW4R	NSD2_HUMAN	Increases Degradation	[8]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[8]
Solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1)	OTA675TJ	GTR1_HUMAN	Decreases Expression	[8]
Glucose-6-phosphate 1-dehydrogenase (G6PD)	OT300SMK	G6PD_HUMAN	Decreases Expression	[8]
Cadherin-1 (CDH1)	OTFJMXPM	CADH1_HUMAN	Increases Expression	[9]
Coilin (COIL)	OTP4I4DL	COIL_HUMAN	Increases Expression	[7]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[7]
Hexokinase-2 (HK2)	OTC0GCQO	HXK2_HUMAN	Decreases Expression	[8]
Cytochrome c (CYCS)	OTBFALJD	CYC_HUMAN	Increases Expression	[8]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[8]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Expression	[8]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1)	OT2YYI1A	MCL1_HUMAN	Decreases Expression	[8]
Histone-lysine N-methyltransferase EZH2 (EZH2)	OTIEHTKW	EZH2_HUMAN	Decreases Activity	[10]
Transcriptional protein SWT1 (SWT1)	OTY4AFM1	SWT1_HUMAN	Decreases Expression	[7]
Transmembrane protein 87A (TMEM87A)	OT8ATDVX	TM87A_HUMAN	Increases Expression	[7]
Dapper homolog 3 (DACT3)	OTSNQ55G	DACT3_HUMAN	Affects Expression	[11]
Fructose-2,6-bisphosphatase TIGAR (TIGAR)	OTR7NMRJ	TIGAR_HUMAN	Decreases Expression	[8]
E3 ubiquitin-protein ligase Jade-2 (JADE2)	OTVG2MYF	JADE2_HUMAN	Increases Expression	[7]
Kelch-like protein 42 (KLHL42)	OTK6WARI	KLH42_HUMAN	Increases Expression	[7]
Two pore channel protein 1 (TPCN1)	OTT4C4DI	TPC1_HUMAN	Decreases Expression	[7]
DmX-like protein 1 (DMXL1)	OTWVL31L	DMXL1_HUMAN	Decreases Expression	[7]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Increases Response To Substance	[12]
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⏷ Show the Full List of 24 DOT(s)

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	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: 7349).
3	3-Deazaneplanocin: a new and potent inhibitor of S-adenosylhomocysteine hydrolase and its effects on human promyelocytic leukemia cell line HL-60. Biochem Biophys Res Commun. 1986 Mar 13;135(2):688-94.
4	Clinical pipeline report, company report or official report of Shionogi (2011).
5	Ospemifene metabolism in humans in vitro and in vivo: metabolite identification, quantitation, and CYP assignment of major hydroxylations. Drug Metabol Drug Interact. 2013;28(3):153-61.
6	Effects of ospemifene, a novel selective estrogen-receptor modulator, on human breast tissue ex vivo. Menopause. 2016 Jul;23(7):719-30. doi: 10.1097/GME.0000000000000624.
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	S-adenosylhomocysteine (AdoHcy)-dependent methyltransferase inhibitor DZNep overcomes breast cancer tamoxifen resistance via induction of NSD2 degradation and suppression of NSD2-driven redox homeostasis. Chem Biol Interact. 2020 Feb 1;317:108965. doi: 10.1016/j.cbi.2020.108965. Epub 2020 Jan 28.
9	Methotrexate induces apoptosis through p53/p21-dependent pathway and increases E-cadherin expression through downregulation of HDAC/EZH2. Biochem Pharmacol. 2011 Feb 15;81(4):510-7. doi: 10.1016/j.bcp.2010.11.014. Epub 2010 Nov 27.
10	Upregulation of histone-lysine methyltransferases plays a causal role in hexavalent chromium-induced cancer stem cell-like property and cell transformation. Toxicol Appl Pharmacol. 2018 Mar 1;342:22-30. doi: 10.1016/j.taap.2018.01.022. Epub 2018 Jan 31.
11	DACT3 is an epigenetic regulator of Wnt/beta-catenin signaling in colorectal cancer and is a therapeutic target of histone modifications. Cancer Cell. 2008 Jun;13(6):529-41. doi: 10.1016/j.ccr.2008.04.019.
12	Disruption of the MYC-miRNA-EZH2 loop to suppress aggressive B-cell lymphoma survival and clonogenicity. Leukemia. 2013 Dec;27(12):2341-50. doi: 10.1038/leu.2013.94. Epub 2013 Mar 29.