Details of the Drug Combination

General Information of Drug Combination (ID: DCHXM9M)

• Drug Combination Name: Larotrectinib + PF-562271
• Indication: Diffuse intrinsic pontine glioma; Status: Investigative [1]
• Component Drugs:
  Larotrectinib (DM26CQR): N.A.
  PF-562271 (DMSLE03): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: DIPG25
  Zero Interaction Potency (ZIP) Score: 29.71
  Bliss Independence Score: 34.24
  Loewe Additivity Score: 4.6
  LHighest Single Agent (HSA) Score: 13.59

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Larotrectinib

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

Larotrectinib Interacts with 3 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Tropomyosin-related kinase A (TrkA)	TTTDVOJ	NTRK1_HUMAN	Inhibitor	[4]
NT-3 growth factor receptor (TrkC)	TTXABCW	NTRK3_HUMAN	Inhibitor	[4]
BDNF/NT-3 growth factors receptor (TrkB)	TTKN7QR	NTRK2_HUMAN	Inhibitor	[4]

Indication(s) of PF-562271

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Phase 1	[3]

PF-562271 Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Focal adhesion kinase 1 (FAK)	TTON5IT	FAK1_HUMAN	Inhibitor	[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] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] ClinicalTrials.gov (NCT00666926) Study Of PF-00562271, Including Patients With Pancreatic, Head And Neck, Prostatic Neoplasms. U.S. National Institutes of Health.
• [4] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
• [5] Inhibition of focal adhesion kinase by PF-562,271 inhibits the growth and metastasis of pancreatic cancer concomitant with altering the tumor microenvironment. Mol Cancer Ther. 2011 Nov;10(11):2135-45.