Details of the Drug Combination

General Information of Drug Combination (ID: DCS2HYP)

Drug Combination Name

Abexinostat DZNep

Indication

Disease Entry	Status	REF
Diffuse intrinsic pontine glioma	Investigative	[1]

Component Drugs

Abexinostat DM91LGU

DZNep DM0JXBK

Small molecular drug

2D MOL

3D MOL

3D MOL is unavailable

High-throughput Screening Result

Testing Cell Line: DIPG25

Zero Interaction Potency (ZIP) Score: 1.253

Bliss Independence Score: 1.311

Loewe Additivity Score: 4.567

LHighest Single Agent (HSA) Score: 7.345

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)

Indication(s) of Abexinostat

Disease Entry	ICD 11	Status	REF
Follicular lymphoma	2A80	Phase 3	[2]
Renal cell carcinoma	2C90	Phase 3	[3]
Acute myeloid leukaemia	2A60	Phase 2	[2]
Breast cancer	2C60-2C65	Phase 2	[2]
Diffuse large B-cell lymphoma	2A81	Phase 2	[2]
Gynecologic cancer	2F33-2F76	Phase 2	[2]
Peripheral T-cell lymphoma	2A90.C	Phase 2	[2]
Solid tumour/cancer	2A00-2F9Z	Phase 2	[2]

Abexinostat Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Histone deacetylase (HDAC)	TTBH0VX	NOUNIPROTAC	Modulator	[6]
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Abexinostat Interacts with 15 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB)	OT9RDS3H	IKKB_HUMAN	Decreases Expression	[5]
Growth arrest and DNA damage-inducible protein GADD45 gamma (GADD45G)	OT8V1J4M	GA45G_HUMAN	Increases Expression	[7]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Decreases Expression	[5]
Heme oxygenase 1 (HMOX1)	OTC1W6UX	HMOX1_HUMAN	Increases Expression	[5]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[7]
C-C motif chemokine 3 (CCL3)	OTW2H3ND	CCL3_HUMAN	Decreases Expression	[5]
Nuclear factor NF-kappa-B p105 subunit (NFKB1)	OTNRRD8I	NFKB1_HUMAN	Decreases Expression	[5]
Heme oxygenase 2 (HMOX2)	OTG40XBT	HMOX2_HUMAN	Decreases Expression	[5]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[5]
Breast cancer type 2 susceptibility protein (BRCA2)	OTF1XSV1	BRCA2_HUMAN	Decreases Expression	[7]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Cleavage	[5]
C-C motif chemokine 7 (CCL7)	OTDIS99H	CCL7_HUMAN	Decreases Expression	[5]
Transcription factor RelB (RELB)	OTU3QYEF	RELB_HUMAN	Decreases Expression	[5]
DNA repair protein RAD51 homolog 1 (RAD51)	OTNVWGC1	RAD51_HUMAN	Decreases Expression	[7]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Increases Cleavage	[5]
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⏷ Show the Full List of 15 DOT(s)

Indication(s) of DZNep

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[4]

DZNep Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Adenosylhomocysteinase (AHCY)	TTE2KUJ	SAHH_HUMAN	Inhibitor	[4]
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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	[8]
Histone-lysine N-methyltransferase SUV39H1 (SUV39H1)	OTDTF5BU	SUV91_HUMAN	Increases Expression	[8]
Histone-lysine N-methyltransferase NSD2 (NSD2)	OTQ6SW4R	NSD2_HUMAN	Increases Degradation	[9]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[9]
Solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1)	OTA675TJ	GTR1_HUMAN	Decreases Expression	[9]
Glucose-6-phosphate 1-dehydrogenase (G6PD)	OT300SMK	G6PD_HUMAN	Decreases Expression	[9]
Cadherin-1 (CDH1)	OTFJMXPM	CADH1_HUMAN	Increases Expression	[10]
Coilin (COIL)	OTP4I4DL	COIL_HUMAN	Increases Expression	[8]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[8]
Hexokinase-2 (HK2)	OTC0GCQO	HXK2_HUMAN	Decreases Expression	[9]
Cytochrome c (CYCS)	OTBFALJD	CYC_HUMAN	Increases Expression	[9]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[9]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Expression	[9]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1)	OT2YYI1A	MCL1_HUMAN	Decreases Expression	[9]
Histone-lysine N-methyltransferase EZH2 (EZH2)	OTIEHTKW	EZH2_HUMAN	Decreases Activity	[11]
Transcriptional protein SWT1 (SWT1)	OTY4AFM1	SWT1_HUMAN	Decreases Expression	[8]
Transmembrane protein 87A (TMEM87A)	OT8ATDVX	TM87A_HUMAN	Increases Expression	[8]
Dapper homolog 3 (DACT3)	OTSNQ55G	DACT3_HUMAN	Affects Expression	[12]
Fructose-2,6-bisphosphatase TIGAR (TIGAR)	OTR7NMRJ	TIGAR_HUMAN	Decreases Expression	[9]
E3 ubiquitin-protein ligase Jade-2 (JADE2)	OTVG2MYF	JADE2_HUMAN	Increases Expression	[8]
Kelch-like protein 42 (KLHL42)	OTK6WARI	KLH42_HUMAN	Increases Expression	[8]
Two pore channel protein 1 (TPCN1)	OTT4C4DI	TPC1_HUMAN	Decreases Expression	[8]
DmX-like protein 1 (DMXL1)	OTWVL31L	DMXL1_HUMAN	Decreases Expression	[8]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Increases Response To Substance	[13]
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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	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
3	ClinicalTrials.gov (NCT03592472) A Study of Pazopanib With or Without Abexinostat in Patients With Locally Advanced or Metastatic Renal Cell Carcinoma (RENAVIV). U.S. National Institutes of Health.
4	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.
5	PCI-24781 induces caspase and reactive oxygen species-dependent apoptosis through NF-kappaB mechanisms and is synergistic with bortezomib in lymphoma cells. Clin Cancer Res. 2009 May 15;15(10):3354-65. doi: 10.1158/1078-0432.CCR-08-2365. Epub 2009 May 5.
6	Phase 1 study of the oral histone deacetylase inhibitor abexinostat in patients with Hodgkin lymphoma, non-Hodgkin lymphoma, or chronic lymphocytic leukaemia. Invest New Drugs. 2015 Apr;33(2):423-31.
7	HDAC inhibitor PCI-24781 decreases RAD51 expression and inhibits homologous recombination. Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19482-7. doi: 10.1073/pnas.0707828104. Epub 2007 Nov 27.
8	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.
9	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.
10	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.
11	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.
12	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.
13	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.