Details of the Drug Combination

General Information of Drug Combination (ID: DC0VTEM)

• Drug Combination Name: GDC-0084 + (-)-englerin A
• Indication: Ewing sarcoma; Status: Investigative [1]
• Component Drugs:
  GDC-0084 (DMA9SEY): N.A.
  (-)-englerin A (DMPQBWY): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: TC-71
  Zero Interaction Potency (ZIP) Score: 8.77
  Bliss Independence Score: 7.44
  Loewe Additivity Score: 11.619
  LHighest Single Agent (HSA) Score: 12.264

Molecular Interaction Atlas of This Drug Combination

Indication(s) of GDC-0084

Disease Entry	ICD 11	Status	REF
Glioblastoma of brain	2A00.00	Phase 2	[2]

GDC-0084 Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
PI3-kinase gamma (PIK3CG)	TTHBTOP	PK3CG_HUMAN	Inhibitor	[4]

Indication(s) of (-)-englerin A

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[3]

(-)-englerin A Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Short transient receptor potential channel 5 (TRPC5)	TT32NQ1	TRPC5_HUMAN	Agonist	[5]
Short transient receptor potential channel 4 (TRPC4)	TTX0H5W	TRPC4_HUMAN	Agonist	[5]

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 (NCT03522298) Safety, Pharmacokinetics and Efficacy of Paxalisib (GDC-0084) in Newly-diagnosed Glioblastoma. U.S. National Institutes of Health.
• [3] Enantioselective synthesis of (-)-englerins A and B. Angew Chem Int Ed Engl. 2010 May 3;49(20):3517-9.
• [4] Current clinical development of PI3K pathway inhibitors in glioblastoma. Neuro Oncol. 2012 July; 14(7): 819-829.
• [5] (-)-Englerin is a potent and selective activator of TRPC4 and TRPC5 calcium channels. Angew Chem Int Ed Engl. 2015 Mar 16;54(12):3787-91.