Details of the Drug Combination

General Information of Drug Combination (ID: DCPVTPZ)

Drug Combination Name

Ribavirin-TP LY2835219

Indication

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

Component Drugs

Ribavirin-TP DM09NGV

LY2835219 DM93VBZ

Small molecular drug

2D MOL

3D MOL

3D MOL is unavailable

High-throughput Screening Result

Testing Cell Line: DIPG25

Zero Interaction Potency (ZIP) Score: 5.62

Bliss Independence Score: 14.07

Loewe Additivity Score: 6.04

LHighest Single Agent (HSA) Score: 5.59

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)

Indication(s) of Ribavirin-TP

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

Ribavirin-TP Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Hepatitis C virus NS3 helicase (HCV NS3)	TTWXB3E	POLG_HCV1	Inhibitor	[2]
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Indication(s) of LY2835219

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Approved	[3]
Solid tumour/cancer	2A00-2F9Z	Phase 3	[4]

LY2835219 Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Cyclin-dependent kinase 4 (CDK4)	TT0PG8F	CDK4_HUMAN	Modulator	[6]
Cyclin-dependent kinase 6 (CDK6)	TTO0FDJ	CDK6_HUMAN	Modulator	[6]
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LY2835219 Interacts with 3 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Organic cation transporter 2 (SLC22A2)	DT9IDPW	S22A2_HUMAN	Substrate	[7]
Multidrug and toxin extrusion protein 1 (SLC47A1)	DTZGT0P	S47A1_HUMAN	Substrate	[7]
Multidrug and toxin extrusion protein 2 (SLC47A2)	DT3TX4H	S47A2_HUMAN	Substrate	[7]
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LY2835219 Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[8]
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LY2835219 Interacts with 27 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Tripeptidyl-peptidase 1 (TPP1)	OT2LQ771	TPP1_HUMAN	Increases Expression	[5]
Glutaminase kidney isoform, mitochondrial (GLS)	OTGOZG2M	GLSK_HUMAN	Increases Expression	[5]
G2/mitotic-specific cyclin-B2 (CCNB2)	OTIEXTDK	CCNB2_HUMAN	Decreases Expression	[5]
Securin (PTTG1)	OTIMYS4W	PTTG1_HUMAN	Decreases Expression	[5]
G1/S-specific cyclin-E2 (CCNE2)	OTBBUKQQ	CCNE2_HUMAN	Decreases Expression	[9]
Apolipoprotein E (APOE)	OTFOWL2H	APOE_HUMAN	Increases Expression	[5]
Fibrinogen beta chain (FGB)	OT6RKLI9	FIBB_HUMAN	Decreases Expression	[5]
Fibrinogen gamma chain (FGG)	OT5BJSEX	FIBG_HUMAN	Decreases Expression	[5]
N-myc proto-oncogene protein (MYCN)	OTWD33K1	MYCN_HUMAN	Decreases Expression	[5]
Retinoblastoma-associated protein (RB1)	OTQJUJMZ	RB_HUMAN	Decreases Expression	[9]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Decreases Activity	[10]
Gamma-enolase (ENO2)	OTRODL0T	ENOG_HUMAN	Increases Expression	[5]
SPARC (SPARC)	OTPN90H0	SPRC_HUMAN	Increases Expression	[5]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Affects Expression	[11]
Cyclin-A2 (CCNA2)	OTPHHYZJ	CCNA2_HUMAN	Decreases Expression	[9]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Affects Expression	[11]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[5]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Expression	[11]
Ran-specific GTPase-activating protein (RANBP1)	OTQE226K	RANG_HUMAN	Decreases Expression	[5]
Proliferation marker protein Ki-67 (MKI67)	OTA8N1QI	KI67_HUMAN	Decreases Expression	[5]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Affects Expression	[11]
Ephrin-B3 (EFNB3)	OT12WTXQ	EFNB3_HUMAN	Decreases Expression	[5]
Insulin growth factor-like family member 2 (IGFL2)	OT64M0K7	IGFL2_HUMAN	Increases Expression	[5]
BRCA1-associated RING domain protein 1 (BARD1)	OTTC0Z9Y	BARD1_HUMAN	Decreases Expression	[5]
Fanconi anemia group E protein (FANCE)	OTKRPBW1	FANCE_HUMAN	Decreases Expression	[5]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2)	OTW8V2V1	ABCG2_HUMAN	Decreases Activity	[10]
Transforming acidic coiled-coil-containing protein 3 (TACC3)	OTRNEZTA	TACC3_HUMAN	Decreases Expression	[5]
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⏷ Show the Full List of 27 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	ATP-binding domain of NTPase/helicase as a target for hepatitis C antiviral therapy. Acta Biochim Pol. 2000;47(1):173-80.
3	2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
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: 7382).
5	Biological specificity of CDK4/6 inhibitors: dose response relationship, in vivo signaling, and composite response signature. Oncotarget. 2017 Jul 4;8(27):43678-43691. doi: 10.18632/oncotarget.18435.
6	Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
7	Abemaciclib Inhibits Renal Tubular Secretion Without Changing Glomerular Filtration Rate. Clin Pharmacol Ther. 2019 May;105(5):1187-1195.
8	LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]-Abemaciclib.
9	CDK4/6 Inhibition Controls Proliferation of Bladder Cancer and Transcription of RB1. J Urol. 2016 Mar;195(3):771-9. doi: 10.1016/j.juro.2015.08.082. Epub 2015 Aug 28.
10	Effect of abemaciclib (LY2835219) on enhancement of chemotherapeutic agents in ABCB1 and ABCG2 overexpressing cells in vitro and in vivo. Biochem Pharmacol. 2017 Jan 15;124:29-42. doi: 10.1016/j.bcp.2016.10.015. Epub 2016 Nov 2.
11	In vitro therapeutic effects of abemaciclib on triple-negative breast cancer cells. J Biochem Mol Toxicol. 2021 Sep;35(9):e22858. doi: 10.1002/jbt.22858. Epub 2021 Jul 26.