Details of the Drug Combination

General Information of Drug Combination (ID: DCOGN22)

Drug Combination Name
Zarnestra PF-562271
Indication
Disease Entry Status REF
Diffuse large B cell lymphoma Investigative [1]
Component Drugs Zarnestra   DMF30HL PF-562271   DMSLE03
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: TMD8
Zero Interaction Potency (ZIP) Score: 16.31
Bliss Independence Score: 19.54
Loewe Additivity Score: 9.91
LHighest Single Agent (HSA) Score: 11.56

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Zarnestra
Disease Entry ICD 11 Status REF
Acute myeloid leukaemia 2A60 Phase 3 [2]
Chronic myelogenous leukaemia 2A20.0 Phase 2 [3]
Human papillomavirus infection 1A9Y Phase 2 [3]
Myelodysplastic syndrome 2A37 Phase 2 [3]
Peripheral T-cell lymphoma 2A90.C Phase 2 [3]
Colorectal cancer 2B91.Z Phase 1/2 [4]
Pancreatic cancer 2C10 Phase 1/2 [4]
Zarnestra Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Farnesyl protein transferase (Ftase) TTXQKM3 FNTA_HUMAN; FNTB_HUMAN Modulator [6]
Geranyltranstransferase (FDPS) TTIKWV4 FPPS_HUMAN Inhibitor [3]
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Zarnestra Interacts with 4 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
GTPase HRas (HRAS) OTWQN0DP RASH_HUMAN Decreases Metabolism [7]
Granulocyte-macrophage colony-stimulating factor (CSF2) OT1M7D28 CSF2_HUMAN Decreases Activity [8]
GTP-binding protein Rheb (RHEB) OTFLTSEC RHEB_HUMAN Decreases Activity [9]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Affects Response To Substance [10]
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Indication(s) of PF-562271
Disease Entry ICD 11 Status REF
Solid tumour/cancer 2A00-2F9Z Phase 1 [5]
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 [11]
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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 (NCT00093990) Tipifarnib Versus Best Supportive Care in the Treatment of Newly Diagnosed Acute Myeloid Leukemia (AML). U.S. National Institutes of Health.
3 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
4 Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127.
5 ClinicalTrials.gov (NCT00666926) Study Of PF-00562271, Including Patients With Pancreatic, Head And Neck, Prostatic Neoplasms. U.S. National Institutes of Health.
6 Tipifarnib in the treatment of newly diagnosed acute myelogenous leukemia. Biologics. 2008 Sep;2(3):491-500.
7 Farnesyltransferase inhibitor R115777 (Zarnestra, Tipifarnib) synergizes with paclitaxel to induce apoptosis and mitotic arrest and to inhibit tumor growth of multiple myeloma cells. Blood. 2005 Jun 15;105(12):4759-66. doi: 10.1182/blood-2004-11-4307. Epub 2005 Feb 22.
8 Genetic disruption of the PI3K regulatory subunits, p85, p55, and p50, normalizes mutant PTPN11-induced hypersensitivity to GM-CSF. Haematologica. 2012 Jul;97(7):1042-7. doi: 10.3324/haematol.2011.046896. Epub 2012 Feb 7.
9 Ras homologue enriched in brain is a critical target of farnesyltransferase inhibitors in non-small cell lung cancer cells. Cancer Lett. 2010 Nov 1;297(1):117-25. doi: 10.1016/j.canlet.2010.05.004.
10 Pharmacogenetics of tipifarnib (R115777) transport and metabolism in cancer patients. Invest New Drugs. 2004 Aug;22(3):285-9.
11 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.