General Information of Drug Combination (ID: DCZ1UOA)

Drug Combination Name
MK-1775 Daporinad
Indication
Disease Entry Status REF
Diffuse intrinsic pontine glioma Investigative [1]
Component Drugs MK-1775   DM3WDZ5 Daporinad   DMCU74R
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: DIPG25
Zero Interaction Potency (ZIP) Score: 9.324
Bliss Independence Score: 8.758
Loewe Additivity Score: 1.404
LHighest Single Agent (HSA) Score: 7.038

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of MK-1775
Disease Entry ICD 11 Status REF
Ovarian cancer 2C73 Phase 2 [2]
Solid tumour/cancer 2A00-2F9Z Phase 1 [3]
MK-1775 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Wee1-like protein kinase (WEE1) TTJFOAL WEE1_HUMAN Inhibitor [6]
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MK-1775 Interacts with 2 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cyclin-dependent kinase 1 (CDK1) OTW1SC2N CDK1_HUMAN Decreases Phosphorylation [5]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Response To Substance [5]
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Indication(s) of Daporinad
Disease Entry ICD 11 Status REF
leukaemia 2A60-2B33 Phase 2 [4]
Daporinad Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Nicotinamide phosphoribosyltransferase (NAMPT) TTD1WIG NAMPT_HUMAN Inhibitor [7]
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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 [8]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Decreases Expression [8]
Catenin beta-1 (CTNNB1) OTZ932A3 CTNB1_HUMAN Decreases Expression [8]
Nicotinate phosphoribosyltransferase (NAPRT) OTVVN0SL PNCB_HUMAN Decreases Activity [9]
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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: 7702).
3 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
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: 7745).
5 Functional kinomics identifies candidate therapeutic targets in head and neck cancer. Clin Cancer Res. 2014 Aug 15;20(16):4274-88. doi: 10.1158/1078-0432.CCR-13-2858.
6 A novel c-Met inhibitor, MK8033, synergizes with carboplatin plus paclitaxel to inhibit ovarian cancer cell growth. Oncol Rep. 2013 May;29(5):2011-8.
7 Anticancer agent CHS-828 inhibits cellular synthesis of NAD. Biochem Biophys Res Commun. 2008 Mar 21;367(4):799-804.
8 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.
9 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.