Details of the Drug Combination

General Information of Drug Combination (ID: DCK0EF9)

Drug Combination Name
Larotrectinib Daporinad
Indication
Disease Entry Status REF
Diffuse intrinsic pontine glioma Investigative [1]
Component Drugs Larotrectinib   DM26CQR Daporinad   DMCU74R
N.A. Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: DIPG25
Zero Interaction Potency (ZIP) Score: 18.58
Bliss Independence Score: 16.673
Loewe Additivity Score: 0.622
LHighest Single Agent (HSA) Score: 1.734

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Larotrectinib
Disease Entry ICD 11 Status REF
Solid tumour/cancer 2A00-2F9Z Approved [2]
Larotrectinib Interacts with 3 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Tropomyosin-related kinase A (TrkA) TTTDVOJ NTRK1_HUMAN Inhibitor [4]
NT-3 growth factor receptor (TrkC) TTXABCW NTRK3_HUMAN Inhibitor [4]
BDNF/NT-3 growth factors receptor (TrkB) TTKN7QR NTRK2_HUMAN Inhibitor [4]
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Indication(s) of Daporinad
Disease Entry ICD 11 Status REF
leukaemia 2A60-2B33 Phase 2 [3]
Daporinad Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Nicotinamide phosphoribosyltransferase (NAMPT) TTD1WIG NAMPT_HUMAN Inhibitor [5]
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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 [6]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Decreases Expression [6]
Catenin beta-1 (CTNNB1) OTZ932A3 CTNB1_HUMAN Decreases Expression [6]
Nicotinate phosphoribosyltransferase (NAPRT) OTVVN0SL PNCB_HUMAN Decreases Activity [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 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
3 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).
4 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
5 Anticancer agent CHS-828 inhibits cellular synthesis of NAD. Biochem Biophys Res Commun. 2008 Mar 21;367(4):799-804.
6 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.
7 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.