Details of the Drug Combination

General Information of Drug Combination (ID: DCJS465)

Drug Combination Name
JNK-IN-8 Mepacrine
Indication
Disease Entry Status REF
Lung adenocarcinoma Investigative [1]
Component Drugs JNK-IN-8   DMLWYJB Mepacrine   DMU8L7C
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL is unavailable 3D MOL
High-throughput Screening Result Testing Cell Line: NCI-H522
Zero Interaction Potency (ZIP) Score: 4.27
Bliss Independence Score: 2.47
Loewe Additivity Score: 0.26
LHighest Single Agent (HSA) Score: 3.41

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of JNK-IN-8
Disease Entry ICD 11 Status REF
Discovery agent N.A. Investigative [2]
JNK-IN-8 Interacts with 3 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Stress-activated protein kinase JNK3 (JNK3) TT056SO MK10_HUMAN Inhibitor [2]
JNK2 messenger RNA (JNK2 mRNA) TT3IVG2 MK09_HUMAN Inhibitor [2]
Stress-activated protein kinase JNK1 (JNK1) TT0K6EO MK08_HUMAN Inhibitor [2]
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JNK-IN-8 Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cell division cycle and apoptosis regulator protein 1 (CCAR1) OTUXLQZZ CCAR1_HUMAN Increases Expression [4]
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Indication(s) of Mepacrine
Disease Entry ICD 11 Status REF
Discovery agent N.A. Investigative [3]
Mepacrine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Phospholipase A2 (PLA2G1B) TT9V5JH PA21B_HUMAN Inhibitor [3]
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Mepacrine Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [5]
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Mepacrine Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [6]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [6]
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Mepacrine Interacts with 11 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Myc proto-oncogene protein (MYC) OTPV5LUK MYC_HUMAN Decreases Expression [7]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [8]
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 (PLCG1) OTSBQR6D PLCG1_HUMAN Decreases Phosphorylation [9]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [8]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [8]
Catenin beta-1 (CTNNB1) OTZ932A3 CTNB1_HUMAN Decreases Expression [7]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Decreases Expression [10]
Casein kinase I isoform alpha (CSNK1A1) OTJ6O1IC KC1A_HUMAN Increases Expression [7]
Forkhead box protein P3 (FOXP3) OTA9Z9OC FOXP3_HUMAN Increases Expression [8]
F-box/WD repeat-containing protein 1A (BTRC) OT2EZDGR FBW1A_HUMAN Decreases Expression [8]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Transport [6]
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⏷ Show the Full List of 11 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Renal cell carcinoma DC67NXJ UO-31 Investigative [11]
Lung adenocarcinoma DCOMS2B EKVX Investigative [1]
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References

1 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125976
2 Discovery of potent and selective covalent inhibitors of JNK. Chem Biol. 2012 Jan 27;19(1):140-54.
3 Involvement of protein kinase C activation in L-leucine-induced stimulation of protein synthesis in l6 myotubes. Cytotechnology. 2003 Nov;43(1-3):97-103.
4 A H2AX?CARP-1 Interaction Regulates Apoptosis Signaling Following DNA Damage. Cancers (Basel). 2019 Feb 14;11(2):221. doi: 10.3390/cancers11020221.
5 Arginine-482 is not essential for transport of antibiotics, primary bile acids and unconjugated sterols by the human breast cancer resistance protein (ABCG2). Biochem J. 2005 Jan 15;385(Pt 2):419-26.
6 Quinacrine is mainly metabolized to mono-desethyl quinacrine by CYP3A4/5 and its brain accumulation is limited by P-glycoprotein. Drug Metab Dispos. 2006 Jul;34(7):1136-44.
7 Nanoquinacrine caused apoptosis in oral cancer stem cells by disrupting the interaction between GLI1 and catenin through activation of GSK3. Toxicol Appl Pharmacol. 2017 Sep 1;330:53-64. doi: 10.1016/j.taap.2017.07.008. Epub 2017 Jul 15.
8 Quinacrine induces the apoptosis of human leukemia U937 cells through FOXP3/miR-183/-TrCP/SP1 axis-mediated BAX upregulation. Toxicol Appl Pharmacol. 2017 Nov 1;334:35-46. doi: 10.1016/j.taap.2017.08.019. Epub 2017 Sep 1.
9 Quinacrine is active in preclinical models of glioblastoma through suppressing angiogenesis, inducing oxidative stress and activating AMPK. Toxicol In Vitro. 2022 Sep;83:105420. doi: 10.1016/j.tiv.2022.105420. Epub 2022 Jun 17.
10 Multiple-endpoint in vitro carcinogenicity test in human cell line TK6 distinguishes carcinogens from non-carcinogens and highlights mechanisms of action. Arch Toxicol. 2021 Jan;95(1):321-336. doi: 10.1007/s00204-020-02902-3. Epub 2020 Sep 10.
11 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966