Details of the Drug Combination

General Information of Drug Combination (ID: DC3EM7S)

• Drug Combination Name: OSI-027 + (-)-englerin A
• Indication: Ewing sarcoma; Status: Investigative [1]
• Component Drugs:
  OSI-027 (DMJX3O8): Small molecular drug
  (-)-englerin A (DMPQBWY): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: TC-71
  Zero Interaction Potency (ZIP) Score: 5.667
  Bliss Independence Score: 4.794
  Loewe Additivity Score: 7.417
  LHighest Single Agent (HSA) Score: 10.791

Molecular Interaction Atlas of This Drug Combination

Indication(s) of OSI-027

Disease Entry	ICD 11	Status	REF
Renal cell carcinoma	2C90	Phase 2	[2]

OSI-027 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]

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] Preclinical characterization of OSI-027, a potent and selective inhibitor of mTORC1 and mTORC2: distinct from rapamycin. Mol Cancer Ther. 2011 Aug;10(8):1394-406.
• [3] Enantioselective synthesis of (-)-englerins A and B. Angew Chem Int Ed Engl. 2010 May 3;49(20):3517-9.
• [4] Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov. 2009 Aug;8(8):627-44.
• [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.