Details of the Drug Combination

General Information of Drug Combination (ID: DCHG9OK)

• Drug Combination Name: AZD8055 + Podofilox
• Indication: Glioblastoma; Status: Investigative [1]
• Component Drugs:
  AZD8055 (DM7L8SG): Small molecular drug
  Podofilox (DMT2EJP): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: JHH-136
  Zero Interaction Potency (ZIP) Score: 22.037
  Bliss Independence Score: 24.785
  Loewe Additivity Score: 2.549
  LHighest Single Agent (HSA) Score: 8.027

Molecular Interaction Atlas of This Drug Combination

Indication(s) of AZD8055

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 1/2	[2]

AZD8055 Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Serine/threonine-protein kinase mTOR (mTOR)	TTCJG29	MTOR_HUMAN	Inhibitor	[4]

AZD8055 Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Ribosomal protein S6 kinase beta-1 (RPS6KB1)	OTAELNGX	KS6B1_HUMAN	Decreases Phosphorylation	[5]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Decreases Phosphorylation	[5]

Indication(s) of Podofilox

Disease Entry	ICD 11	Status	REF
Condyloma	1A95	Approved	[3]
External genital and perianal wart	1A95	Approved	[3]
Verruca vulgaris	1E80	Approved	[3]

Podofilox 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	Modulator	[6]

Podofilox Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[7]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[7]

Podofilox Interacts with 5 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[8]
Microtubule-associated protein tau (MAPT)	OTMTP2Z7	TAU_HUMAN	Decreases Expression	[9]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[8]
Caspase-2 (CASP2)	OTUDYSPP	CASP2_HUMAN	Increases Activity	[8]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Activity	[8]

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: 7714).
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [4] Clinical pipeline report, company report or official report of AstraZeneca (2009).
• [5] Frenolicin B Targets Peroxiredoxin 1 and Glutaredoxin 3 to Trigger ROS/4E-BP1-Mediated Antitumor Effects. Cell Chem Biol. 2019 Mar 21;26(3):366-377.e12. doi: 10.1016/j.chembiol.2018.11.013. Epub 2019 Jan 17.
• [6] Antitumor properties of podophyllotoxin and related compounds. Curr Pharm Des. 2000 Dec;6(18):1811-39.
• [7] Characterization of in vitro metabolites of deoxypodophyllotoxin in human and rat liver microsomes using liquid chromatography/tandem mass spectrometry. Rapid Commun Mass Spectrom. 2008;22(1):52-8.
• [8] Polyalkoxybenzenes from plants. 5. Parsley seed extract in synthesis of azapodophyllotoxins featuring strong tubulin destabilizing activity in the sea urchin embryo and cell culture assays. J Med Chem. 2011 Oct 27;54(20):7138-49. doi: 10.1021/jm200737s. Epub 2011 Sep 29.
• [9] Pharmacologic reductions of total tau levels; implications for the role of microtubule dynamics in regulating tau expression. Mol Neurodegener. 2006 Jul 26;1:6. doi: 10.1186/1750-1326-1-6.