Details of the Drug Combination

General Information of Drug Combination (ID: DCIOT0N)

Drug Combination Name
Piperazinyl methyl quinazolinone derivative 2 Marizomib
Indication
Disease Entry Status REF
Diffuse intrinsic pontine glioma Investigative [1]
Component Drugs Piperazinyl methyl quinazolinone derivative 2   DM913KS 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: 3.11
Bliss Independence Score: 3.63
Loewe Additivity Score: 2.34
LHighest Single Agent (HSA) Score: 2.82

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Piperazinyl methyl quinazolinone derivative 2 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Sigma intracellular receptor 2 (TMEM97) TT9NXW4 SGMR2_HUMAN Ligand [7]
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Piperazinyl methyl quinazolinone derivative 2 Interacts with 18 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Prostaglandin G/H synthase 2 (PTGS2) OT75U9M4 PGH2_HUMAN Increases Expression [8]
Lathosterol oxidase (SC5D) OT41KMW4 SC5D_HUMAN Increases Expression [6]
Metalloproteinase inhibitor 1 (TIMP1) OTOXC51H TIMP1_HUMAN Decreases Expression [6]
Transferrin receptor protein 1 (TFRC) OT8ZPBDL TFR1_HUMAN Increases Expression [9]
Collagen alpha-2(I) chain (COL1A2) OTY7G382 CO1A2_HUMAN Increases Expression [6]
Biglycan (BGN) OT3AV6IF PGS1_HUMAN Decreases Expression [6]
Phospholipid hydroperoxide glutathione peroxidase GPX4 (GPX4) OTRAFFX2 GPX4_HUMAN Decreases Expression [9]
DNA mismatch repair protein Msh2 (MSH2) OT10H1AB MSH2_HUMAN Increases Expression [6]
Proliferation marker protein Ki-67 (MKI67) OTA8N1QI KI67_HUMAN Decreases Expression [6]
Sestrin-2 (SESN2) OT889IXY SESN2_HUMAN Increases Expression [9]
TATA box-binding protein-associated factor RNA polymerase I subunit A (TAF1A) OTEH7OFT TAF1A_HUMAN Decreases Expression [6]
Acrosin-binding protein (ACRBP) OT0MK3L1 ACRBP_HUMAN Increases Expression [6]
Solute carrier family 40 member 1 (SLC40A1) OT8RV2VY S40A1_HUMAN Increases Expression [9]
Denticleless protein homolog (DTL) OTC29RYE DTL_HUMAN Increases Expression [6]
Cystine/glutamate transporter (SLC7A11) OTKJ6PXW XCT_HUMAN Decreases Expression [10]
Fumarate hydratase, mitochondrial (FH) OTEQWU6Q FUMH_HUMAN Decreases Response To Substance [11]
Serine/threonine-protein kinase D2 (PRKD2) OTIFSVI8 KPCD2_HUMAN Affects Response To Substance [12]
GTPase HRas (HRAS) OTWQN0DP RASH_HUMAN Increases Response To Substance [5]
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⏷ Show the Full List of 18 DOT(s)
Indication(s) of Marizomib
Disease Entry ICD 11 Status REF
Glioblastoma of brain 2A00.00 Phase 3 [2]
Malignant glioma 2A00.0 Phase 1 [3]
Multiple myeloma 2A83 Phase 1 [3]
Solid tumour/cancer 2A00-2F9Z Phase 1 [4]
Marizomib Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Proteasome (PS) TTU7ZMG NOUNIPROTAC Inhibitor [13]
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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 ClinicalTrials.gov (NCT03345095) A Phase III Trial of With Marizomib in Patients With Newly Diagnosed Glioblastoma (MIRAGE). U.S. National Institutes of Health.
3 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
4 Clinical pipeline report, company report or official report of Triphase Accelerator .
5 RAS-RAF-MEK-dependent oxidative cell death involving voltage-dependent anion channels. Nature. 2007 Jun 14;447(7146):864-8. doi: 10.1038/nature05859.
6 A novel circular RNA confers trastuzumab resistance in human epidermal growth factor receptor 2-positive breast cancer through regulating ferroptosis. Environ Toxicol. 2022 Jul;37(7):1597-1607. doi: 10.1002/tox.23509. Epub 2022 Mar 2.
7 The sigma-2 (-2) receptor: a review of recent patent applications: 2013-2018.Expert Opin Ther Pat. 2018 Sep;28(9):655-663.
8 Regulation of ferroptotic cancer cell death by GPX4. Cell. 2014 Jan 16;156(1-2):317-331.
9 Protective effect of sestrin2 against iron overload and ferroptosis-induced liver injury. Toxicol Appl Pharmacol. 2019 Sep 15;379:114665. doi: 10.1016/j.taap.2019.114665. Epub 2019 Jul 16.
10 Downregulation of Cx43 reduces cisplatin-induced acute renal injury by inhibiting ferroptosis. Food Chem Toxicol. 2021 Dec;158:112672. doi: 10.1016/j.fct.2021.112672. Epub 2021 Nov 13.
11 Fumarate hydratase inactivation in hereditary leiomyomatosis and renal cell cancer is synthetic lethal with ferroptosis induction. Cancer Sci. 2018 Sep;109(9):2757-2766. doi: 10.1111/cas.13701. Epub 2018 Jul 20.
12 Targeting PKD2 aggravates ferritinophagy-mediated ferroptosis via promoting autophagosome-lysosome fusion and enhances efficacy of carboplatin in lung adenocarcinoma. Chem Biol Interact. 2024 Jan 5;387:110794. doi: 10.1016/j.cbi.2023.110794. Epub 2023 Nov 10.
13 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.