Details of the Drug Combination

General Information of Drug Combination (ID: DCKWVMM)

Drug Combination Name
ML323 Novobiocin
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs ML323   DMY91A3 Novobiocin   DMRFWGK
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL is unavailable 3D MOL
High-throughput Screening Result Testing Cell Line: KBM-7
Zero Interaction Potency (ZIP) Score: 17.3
Bliss Independence Score: 17.3
Loewe Additivity Score: 31.13
LHighest Single Agent (HSA) Score: 31.15

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of ML323
Disease Entry ICD 11 Status REF
Solid tumour/cancer 2A00-2F9Z Preclinical [2]
ML323 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Deubiquitinating enzyme 1 (USP1) TTG9MT5 UBP1_HUMAN Inhibitor [4]
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Indication(s) of Novobiocin
Disease Entry ICD 11 Status REF
Bacterial infection 1A00-1C4Z Approved [3]
Novobiocin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
DNA topoisomerase II (TOP2) TT0IHXV TOP2A_HUMAN; TOP2B_HUMAN Inhibitor [5]
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Novobiocin Interacts with 4 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cadherin-2 (CDH2) OTH0Y56P CADH2_HUMAN Decreases Expression [6]
ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 (CD38) OTG0TTX7 CD38_HUMAN Increases Expression [6]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Increases Degradation [7]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2) OTW8V2V1 ABCG2_HUMAN Decreases Activity [8]
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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 Deubiquitylating enzymes and drug discovery: emerging opportunities. Nat Rev Drug Discov. 2018 Jan;17(1):57-78.
3 How many modes of action should an antibiotic have Curr Opin Pharmacol. 2008 Oct;8(5):564-73.
4 Synthesis and structure-activity relationship studies of N-benzyl-2-phenylpyrimidin-4-amine derivatives as potent USP1/UAF1 deubiquitinase inhibitors with anticancer activity against nonsmall cell lung cancer. J Med Chem. 2014 Oct 9;57(19):8099-110.
5 Transcriptional responses of Bacillus subtillis and thuringiensis to antibiotics and anti-tumour drugs. Int J Mol Med. 2009 Jan;23(1):33-9.
6 Novobiocin is a novel inducer of CD38 on cells of the myelomonocytic lineage. Biochim Biophys Acta. 2002 Jan 30;1542(1-3):32-40. doi: 10.1016/s0167-4889(01)00163-x.
7 Inhibiting heat-shock protein 90 reverses sensory hypoalgesia in diabetic mice. ASN Neuro. 2010 Aug 11;2(4):e00040. doi: 10.1042/AN20100015.
8 Interactions between Oroxylin A with the solute carrier transporters and ATP-binding cassette transporters: Drug transporters profile for this flavonoid. Chem Biol Interact. 2020 Jun 1;324:109097. doi: 10.1016/j.cbi.2020.109097. Epub 2020 Apr 16.