Details of the Drug Combination

General Information of Drug Combination (ID: DCYPWVS)

Drug Combination Name
AST-487 Elacridar
Indication
Disease Entry Status REF
Human papillomavirus-related cervical adenocarcinoma Investigative [1]
Component Drugs AST-487   DME76KU Elacridar   DMURVE8
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL is unavailable 3D MOL
High-throughput Screening Result Testing Cell Line: KB-ChR-8-5-11
Zero Interaction Potency (ZIP) Score: 27.64
Bliss Independence Score: 28.433
Loewe Additivity Score: 12.131
LHighest Single Agent (HSA) Score: 14.434

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of AST-487
Disease Entry ICD 11 Status REF
Discovery agent N.A. Investigative [2]
AST-487 Interacts with 4 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Tyrosine-protein kinase Kit (KIT) TTX41N9 KIT_HUMAN Inhibitor [4]
Proto-oncogene c-Ret (RET) TT4DXQT RET_HUMAN Inhibitor [4]
Fms-like tyrosine kinase 3 (FLT-3) TTGJCWZ FLT3_HUMAN Inhibitor [5]
Vascular endothelial growth factor receptor 2 (KDR) TTUTJGQ VGFR2_HUMAN Inhibitor [4]
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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 [6]
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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 [7]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2) OTW8V2V1 ABCG2_HUMAN Decreases Activity [8]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [9]
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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 Antileukemic effects of the novel, mutant FLT3 inhibitor NVP-AST487: effects on PKC412-sensitive and -resistant FLT3-expressing cells. Blood. 2008 Dec 15;112(13):5161-70.
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 The RET kinase inhibitor NVP-AST487 blocks growth and calcitonin gene expression through distinct mechanisms in medullary thyroid cancer cells. Cancer Res. 2007 Jul 15;67(14):6956-64.
5 Comprehensive analysis of kinase inhibitor selectivity. Nat Biotechnol. 2011 Oct 30;29(11):1046-51.
6 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.
7 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.
8 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.
9 Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43.