Details of the Drug Combination

General Information of Drug Combination (ID: DC1O0TR)

Drug Combination Name
Sibutramine Marizomib
Indication
Disease Entry Status REF
Diffuse intrinsic pontine glioma Investigative [1]
Component Drugs Sibutramine   DMFJTDI Marizomib   DME9QGW
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: 6.27
Bliss Independence Score: 6.22
Loewe Additivity Score: 0.62
LHighest Single Agent (HSA) Score: 3.8

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Sibutramine
Disease Entry ICD 11 Status REF
Obesity 5B81 Approved [2]
Sibutramine Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Norepinephrine transporter (NET) TTAWNKZ SC6A2_HUMAN Modulator [6]
Serotonin transporter (SERT) TT3ROYC SC6A4_HUMAN Modulator [6]
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Sibutramine Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [7]
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Sibutramine Interacts with 10 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 2D6 (CYP2D6) OTZJC802 CP2D6_HUMAN Decreases Activity [8]
Cytochrome P450 2B6 (CYP2B6) OTOYO4S7 CP2B6_HUMAN Decreases Activity [8]
Cytochrome P450 2C19 (CYP2C19) OTFMJYYE CP2CJ_HUMAN Decreases Activity [8]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [9]
Proteasome subunit beta type-8 (PSMB8) OTW5XGMF PSB8_HUMAN Decreases Expression [9]
Proteasome subunit beta type-5 (PSMB5) OTOZXAS6 PSB5_HUMAN Decreases Expression [9]
DNA damage-inducible transcript 3 protein (DDIT3) OTI8YKKE DDIT3_HUMAN Increases Expression [9]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [9]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [9]
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 (GNB3) OTA6HYBA GBB3_HUMAN Increases ADR [10]
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⏷ Show the Full List of 10 DOT(s)
Indication(s) of Marizomib
Disease Entry ICD 11 Status REF
Glioblastoma of brain 2A00.00 Phase 3 [3]
Malignant glioma 2A00.0 Phase 1 [4]
Multiple myeloma 2A83 Phase 1 [4]
Solid tumour/cancer 2A00-2F9Z Phase 1 [5]
Marizomib Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Proteasome (PS) TTU7ZMG NOUNIPROTAC Inhibitor [11]
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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: 2586).
3 ClinicalTrials.gov (NCT03345095) A Phase III Trial of With Marizomib in Patients With Newly Diagnosed Glioblastoma (MIRAGE). U.S. National Institutes of Health.
4 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
5 Clinical pipeline report, company report or official report of Triphase Accelerator .
6 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
7 Sibutramine: a serotonin-norepinephrine reuptake-inhibitor for the treatment of obesity. Ann Pharmacother. 1999 Sep;33(9):968-78.
8 Potent inhibition of cytochrome P450 2B6 by sibutramine in human liver microsomes. Chem Biol Interact. 2013 Sep 5;205(1):11-9.
9 Sibutramine provokes apoptosis of aortic endothelial cells through altered production of reactive oxygen and nitrogen species. Toxicol Appl Pharmacol. 2017 Jan 1;314:1-11. doi: 10.1016/j.taap.2016.11.003. Epub 2016 Nov 9.
10 Weight loss and body fat reduction under sibutramine therapy in obesity with the C825T polymorphism in the GNB3 gene. Pharmacogenet Genomics. 2009 Sep;19(9):730-3. doi: 10.1097/FPC.0b013e3283307cf1.
11 Marizomib, a proteasome inhibitor for all seasons: preclinical profile and a framework for clinical trials. Curr Cancer Drug Targets. 2011 Mar;11(3):254-84.