Details of the Drug Combination

General Information of Drug Combination (ID: DC6PX5G)

Drug Combination Name
DFN-15 Mepacrine
Indication
Disease Entry Status REF
Plasma cell myeloma Investigative [1]
Component Drugs DFN-15   DM3BF9B Mepacrine   DMU8L7C
N.A. Small molecular drug
High-throughput Screening Result Testing Cell Line: RPMI-8226
Zero Interaction Potency (ZIP) Score: 1.51
Bliss Independence Score: 9.83
Loewe Additivity Score: 1.3
LHighest Single Agent (HSA) Score: 1.2

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of DFN-15
Disease Entry ICD 11 Status REF
Migraine 8A80 Phase 3 [2]
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]
------------------------------------------------------------------------------------
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 [4]
------------------------------------------------------------------------------------
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 [5]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [5]
------------------------------------------------------------------------------------
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 [6]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [7]
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 (PLCG1) OTSBQR6D PLCG1_HUMAN Decreases Phosphorylation [8]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [7]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [7]
Catenin beta-1 (CTNNB1) OTZ932A3 CTNB1_HUMAN Decreases Expression [6]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Decreases Expression [9]
Casein kinase I isoform alpha (CSNK1A1) OTJ6O1IC KC1A_HUMAN Increases Expression [6]
Forkhead box protein P3 (FOXP3) OTA9Z9OC FOXP3_HUMAN Increases Expression [7]
F-box/WD repeat-containing protein 1A (BTRC) OT2EZDGR FBW1A_HUMAN Decreases Expression [7]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Transport [5]
------------------------------------------------------------------------------------
⏷ 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
Anaplastic large cell lymphoma DC6NPUR SR Investigative [1]
Astrocytoma DCMYGI1 U251 Investigative [1]
Glioblastoma DCGBUB9 SNB-75 Investigative [1]
Carcinoma DCNHXUS MCF7 Investigative [10]
Colon carcinoma DCIJRLK KM12 Investigative [10]
Adenocarcinoma DC9RMJR DU-145 Investigative [11]
Adenocarcinoma DC5M7I7 HCT116 Investigative [11]
Adenocarcinoma DC2UYYO HT29 Investigative [11]
Cutaneous melanoma DCZ8H2X SK-MEL-5 Investigative [11]
High grade ovarian serous adenocarcinoma DCE8EK1 OVCAR-5 Investigative [11]
High grade ovarian serous adenocarcinoma DC4C9X9 NCI\\/ADR-RES Investigative [11]
Lung adenocarcinoma DC25HUA HOP-62 Investigative [11]
Lung adenocarcinoma DCI2KKX NCI-H522 Investigative [11]
Malignant melanoma DC9EKV1 UACC62 Investigative [11]
------------------------------------------------------------------------------------
⏷ Show the Full List of 14 DrugCom(s)

References

1 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
2 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
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 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.
5 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.
6 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.
7 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.
8 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.
9 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.
10 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1126165
11 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125976