Details of the Drug Combination

General Information of Drug Combination (ID: DCGUG9T)

Drug Combination Name
VX-680 LY335979
Indication
Disease Entry Status REF
Human papillomavirus-related cervical adenocarcinoma Investigative [1]
Component Drugs VX-680   DM93YKJ LY335979   DM2KITF
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: KB-ChR-8-5-11
Zero Interaction Potency (ZIP) Score: 28.972
Bliss Independence Score: 30.569
Loewe Additivity Score: 9.862
LHighest Single Agent (HSA) Score: 17.884

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of VX-680
Disease Entry ICD 11 Status REF
Solid tumour/cancer 2A00-2F9Z Phase 2 [2]
VX-680 Interacts with 3 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
LCK tyrosine protein kinase (LCK) TT860QF LCK_HUMAN Inhibitor [4]
Aurora kinase B (AURKB) TT5LS6T AURKB_HUMAN Inhibitor [4]
Aurora kinase A (AURKA) TTPS3C0 AURKA_HUMAN Inhibitor [4]
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VX-680 Interacts with 3 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Aurora kinase A (AURKA) OTMX0HYT AURKA_HUMAN Decreases Phosphorylation [5]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Decreases Phosphorylation [6]
Histone H3-like centromeric protein A (CENPA) OT0NEJ4X CENPA_HUMAN Decreases Phosphorylation [5]
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Indication(s) of LY335979
Disease Entry ICD 11 Status REF
Acute myeloid leukaemia 2A60 Discontinued in Phase 3 [3]
LY335979 Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Multidrug resistance protein 1 (ABCB1) TT3OT40 MDR1_HUMAN Modulator [7]
Multidrug resistance protein 3 (ABCB4) TTJUXV6 MDR3_HUMAN Modulator [7]
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LY335979 Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Decreases Activity [8]
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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 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: 5718).
3 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005159)
4 A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22.
5 Targeting aurora kinase with MK-0457 inhibits ovarian cancer growth. Clin Cancer Res. 2008 Sep 1;14(17):5437-46. doi: 10.1158/1078-0432.CCR-07-4922.
6 Cotreatment with vorinostat enhances activity of MK-0457 (VX-680) against acute and chronic myelogenous leukemia cells. Clin Cancer Res. 2008 Oct 1;14(19):6106-15. doi: 10.1158/1078-0432.CCR-08-0721.
7 A Phase I trial of a potent P-glycoprotein inhibitor, zosuquidar trihydrochloride (LY335979), administered intravenously in combination with doxoru... Clin Cancer Res. 2004 May 15;10(10):3265-72.
8 Clinical disposition, metabolism and in vitro drug-drug interaction properties of omadacycline. Xenobiotica. 2017 Aug;47(8):682-696. doi: 10.1080/00498254.2016.1213465. Epub 2016 Aug 8.