Details of the Drug Combination

General Information of Drug Combination (ID: DCEZP78)

• Drug Combination Name: (-)-englerin A + LY2874455
• Indication: Ewing sarcoma; Status: Investigative [1]
• Component Drugs:
  (-)-englerin A (DMPQBWY): Small molecular drug
  LY2874455 (DMZ0DMY): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: TC-71
  Zero Interaction Potency (ZIP) Score: 0.547
  Bliss Independence Score: 0.229
  Loewe Additivity Score: 7.226
  LHighest Single Agent (HSA) Score: 8.459

Molecular Interaction Atlas of This Drug Combination

Indication(s) of (-)-englerin A

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[2]

(-)-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	[4]
Short transient receptor potential channel 4 (TRPC4)	TTX0H5W	TRPC4_HUMAN	Agonist	[4]

Indication(s) of LY2874455

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Phase 2	[3]

LY2874455 Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Fibroblast growth factor receptor 2 (FGFR2)	TTGJVQM	FGFR2_HUMAN	Modulator	[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] Enantioselective synthesis of (-)-englerins A and B. Angew Chem Int Ed Engl. 2010 May 3;49(20):3517-9.
• [3] 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: 8104).
• [4] (-)-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.
• [5] Company report (Eli Lilly) (drug: LY2874455)