Details of the Drug Combination

General Information of Drug Combination (ID: DCX99EW)

Drug Combination Name

Daporinad Parthenolide

Indication

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

Component Drugs

Daporinad DMCU74R

Parthenolide DMCQBFT

Small molecular drug

2D MOL

3D MOL

High-throughput Screening Result

Testing Cell Line: SU-DIPG-XIII

Zero Interaction Potency (ZIP) Score: 10.121

Bliss Independence Score: 9.466

Loewe Additivity Score: 5.417

LHighest Single Agent (HSA) Score: 6.602

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)

Indication(s) of Daporinad

Disease Entry	ICD 11	Status	REF
leukaemia	2A60-2B33	Phase 2	[2]

Daporinad Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Nicotinamide phosphoribosyltransferase (NAMPT)	TTD1WIG	NAMPT_HUMAN	Inhibitor	[3]
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Daporinad Interacts with 4 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Axin-1 (AXIN1)	OTRGZGZ5	AXIN1_HUMAN	Increases Expression	[4]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Decreases Expression	[4]
Catenin beta-1 (CTNNB1)	OTZ932A3	CTNB1_HUMAN	Decreases Expression	[4]
Nicotinate phosphoribosyltransferase (NAPRT)	OTVVN0SL	PNCB_HUMAN	Decreases Activity	[5]
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Parthenolide Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Inhibitor of nuclear factor kappa-B kinase beta (IKKB)	TTJ3E9X	IKKB_HUMAN	Inhibitor	[6]
Nuclear factor NF-kappa-B (NFKB)	TTSXVID	NFKB1_HUMAN; NFKB2_HUMAN; TF65_HUMAN; RELB_HUMAN; REL_HUMAN	Inhibitor	[7]
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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: 7745).
3	Anticancer agent CHS-828 inhibits cellular synthesis of NAD. Biochem Biophys Res Commun. 2008 Mar 21;367(4):799-804.
4	Targeting the NAD(+) salvage pathway suppresses APC mutation-driven colorectal cancer growth and Wnt/-catenin signaling via increasing Axin level. Cell Commun Signal. 2020 Jan 31;18(1):16. doi: 10.1186/s12964-020-0513-5.
5	FK866, a highly specific noncompetitive inhibitor of nicotinamide phosphoribosyltransferase, represents a novel mechanism for induction of tumor cell apoptosis. Cancer Res. 2003 Nov 1;63(21):7436-42.
6	The anti-inflammatory natural product parthenolide from the medicinal herb Feverfew directly binds to and inhibits IkappaB kinase. Chem Biol. 2001 Aug;8(8):759-66.
7	Hypoxia-induced neutrophil survival is mediated by HIF-1alpha-dependent NF-kappaB activity. J Exp Med. 2005 Jan 3;201(1):105-15.