Details of the Drug Combination

General Information of Drug Combination (ID: DC6SISH)

Drug Combination Name
VX-680 Elacridar
Indication
Disease Entry Status REF
Human papillomavirus-related cervical adenocarcinoma? Investigative [1]
Component Drugs VX-680   DM93YKJ Elacridar   DMURVE8
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: KB-3-1
Zero Interaction Potency (ZIP) Score: 14.034
Bliss Independence Score: 14.504
Loewe Additivity Score: 3.8
LHighest Single Agent (HSA) Score: 4.561

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 Elacridar
Disease Entry ICD 11 Status REF
Solid tumour/cancer 2A00-2F9Z Discontinued in Phase 1 [3]
Elacridar Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Multidrug resistance protein 1 (ABCB1) TT3OT40 MDR1_HUMAN Inhibitor [7]
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Elacridar Interacts with 3 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Decreases Activity [8]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2) OTW8V2V1 ABCG2_HUMAN Decreases Activity [9]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [10]
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Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Human papillomavirus-related cervical adenocarcinoma DCOAOP9 KB-ChR-8-5-11 Investigative [1]
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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 800002537)
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 2-[(3-Methoxyphenylethyl)phenoxy]-based ABCB1 inhibitors: effect of different basic side-chains on their biological properties. J Med Chem. 2008 Dec 11;51(23):7602-13.
8 Human organic anion-transporting polypeptide OATP-A (SLC21A3) acts in concert with P-glycoprotein and multidrug resistance protein 2 in the vectorial transport of Saquinavir in Hep G2 cells. Mol Pharm. 2004 Jan 12;1(1):49-56.
9 Flavonoid structure-activity studies identify 6-prenylchrysin and tectochrysin as potent and specific inhibitors of breast cancer resistance protein ABCG2. Cancer Res. 2005 Jun 1;65(11):4852-60.
10 Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43.