Details of the Drug Combination

General Information of Drug Combination (ID: DC6PA4H)

Drug Combination Name

(-)-englerin A AT7519

Indication

Disease Entry	Status	REF
Ewing sarcoma	Investigative	[1]

Component Drugs

(-)-englerin A DMPQBWY

AT7519 DMCE08M

Small molecular drug

2D MOL

3D MOL is unavailable

3D MOL

High-throughput Screening Result

Testing Cell Line: TC-71

Zero Interaction Potency (ZIP) Score: 11.403

Bliss Independence Score: 11.486

Loewe Additivity Score: 1.744

LHighest Single Agent (HSA) Score: 8.488

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)

Indication(s) of (-)-englerin A

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[2]

(-)-englerin A Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Short transient receptor potential channel 5 (TRPC5)	TT32NQ1	TRPC5_HUMAN	Agonist	[4]
Short transient receptor potential channel 4 (TRPC4)	TTX0H5W	TRPC4_HUMAN	Agonist	[4]
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Indication(s) of AT7519

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Phase 1	[3]

AT7519 Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Cyclin-dependent kinase 2 (CDK2)	TT7HF4W	CDK2_HUMAN	Inhibitor	[5]
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AT7519 Interacts with 11 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Forkhead box protein O3 (FOXO3)	OTHXQG4P	FOXO3_HUMAN	Increases Expression	[6]
Ubiquitin-like modifier-activating enzyme ATG7 (ATG7)	OTVT4YA1	ATG7_HUMAN	Decreases Expression	[6]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Decreases Expression	[6]
M-phase inducer phosphatase 1 (CDC25A)	OTSLKKCO	MPIP1_HUMAN	Decreases Expression	[6]
M-phase inducer phosphatase 2 (CDC25B)	OT12MSRY	MPIP2_HUMAN	Decreases Expression	[6]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[6]
Cyclin-dependent kinase inhibitor 1B (CDKN1B)	OTNY5LLZ	CDN1B_HUMAN	Increases Expression	[6]
Forkhead box protein O4 (FOXO4)	OT90X9LN	FOXO4_HUMAN	Increases Expression	[6]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[6]
Bcl2-associated agonist of cell death (BAD)	OT63ERYM	BAD_HUMAN	Increases Expression	[6]
Ubiquitin-like-conjugating enzyme ATG10 (ATG10)	OTVRPC5X	ATG10_HUMAN	Decreases Expression	[6]
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⏷ Show the Full List of 11 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	Enantioselective synthesis of (-)-englerins A and B. Angew Chem Int Ed Engl. 2010 May 3;49(20):3517-9.
3	ClinicalTrials.gov (NCT02503709) Onalespib and CDKI AT7519 in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery in National Cancer Institute (NCI).
4	(-)-Englerin is a potent and selective activator of TRPC4 and TRPC5 calcium channels. Angew Chem Int Ed Engl. 2015 Mar 16;54(12):3787-91.
5	Biological characterization of AT7519, a small-molecule inhibitor of cyclin-dependent kinases, in human tumor cell lines. Mol Cancer Ther. 2009 Feb;8(2):324-32.
6	CDK Blockade Using AT7519 Suppresses Acute Myeloid Leukemia Cell Survival through the Inhibition of Autophagy and Intensifies the Anti-leukemic Effect of Arsenic Trioxide. Iran J Pharm Res. 2019 Fall;18(Suppl1):119-131. doi: 10.22037/ijpr.2019.112560.13827.