Details of the Drug Combination

General Information of Drug Combination (ID: DCH046X)

Drug Combination Name
Artemether KN-62
Indication
Disease Entry Status REF
DD2 Investigative [1]
Component Drugs Artemether   DM48QOT KN-62   DMLZ89P
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL is unavailable
High-throughput Screening Result Testing Cell Line: DD2
Zero Interaction Potency (ZIP) Score: 15.447
Bliss Independence Score: 20.093
Loewe Additivity Score: 0.58
LHighest Single Agent (HSA) Score: 4.565

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Artemether
Disease Entry ICD 11 Status REF
Malaria 1F40-1F45 Approved [2]
Artemether Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Sodium pump subunit alpha-1 (ATP1A1) TTWK8D0 AT1A1_HUMAN Binder [2]
------------------------------------------------------------------------------------
Artemether Interacts with 6 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [4]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [5]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [6]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [7]
Cytochrome P450 2B6 (CYP2B6) DEPKLMQ CP2B6_HUMAN Metabolism [8]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [5]
------------------------------------------------------------------------------------
⏷ Show the Full List of 6 DME(s)
Artemether Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Nuclear receptor subfamily 1 group I member 3 (NR1I3) OTS3SGH7 NR1I3_HUMAN Affects Expression [9]
------------------------------------------------------------------------------------
Indication(s) of KN-62
Disease Entry ICD 11 Status REF
Discovery agent N.A. Investigative [3]
KN-62 Interacts with 13 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
LCK tyrosine protein kinase (LCK) TT860QF LCK_HUMAN Inhibitor [10]
Protein kinase C alpha (PRKCA) TTFJ8Q1 KPCA_HUMAN Inhibitor [10]
Stress-activated protein kinase JNK1 (JNK1) TT0K6EO MK08_HUMAN Inhibitor [10]
Rho-associated protein kinase 1 (ROCK1) TTZN7RP ROCK1_HUMAN Inhibitor [10]
Stress-activated protein kinase 2b (p38 beta) TT73U6C MK11_HUMAN Inhibitor [10]
Extracellular signal-regulated kinase 2 (ERK2) TT4TQBX MK01_HUMAN Inhibitor [10]
Checkpoint kinase-1 (CHK1) TTTU902 CHK1_HUMAN Inhibitor [10]
P2X purinoceptor 7 (P2RX7) TT473XN P2RX7_HUMAN Inhibitor [11]
Serine/threonine-protein kinase Sgk1 (SGK1) TTTV8EJ SGK1_HUMAN Inhibitor [10]
Stress-activated protein kinase 2a (p38 alpha) TTQBR95 MK14_HUMAN Inhibitor [10]
RAC-alpha serine/threonine-protein kinase (AKT1) TTWTSCV AKT1_HUMAN Inhibitor [10]
MAP kinase p38 (MAPK12) TTYT93M MK12_HUMAN Inhibitor [10]
Ribosomal protein S6 kinase beta-1 (S6K1) TTG0U4H KS6B1_HUMAN Inhibitor [10]
------------------------------------------------------------------------------------
⏷ Show the Full List of 13 DTT(s)
KN-62 Interacts with 4 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
MAP kinase-activated protein kinase 2 (MAPKAPK2) OT460SBO MAPK2_HUMAN Decreases Activity [10]
Glycogen synthase kinase-3 beta (GSK3B) OTL3L14B GSK3B_HUMAN Decreases Activity [10]
MAP kinase-activated protein kinase 5 (MAPKAPK5) OTAZHPVK MAPK5_HUMAN Decreases Activity [10]
Integrin alpha-M (ITGAM) OTAG6HWU ITAM_HUMAN Increases Expression [12]
------------------------------------------------------------------------------------

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 The fight against drug-resistant malaria: novel plasmodial targets and antimalarial drugs. Curr Med Chem. 2008;15(2):161-71.
3 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: 6001).
4 The effect of grapefruit juice on the time-dependent decline of artemether plasma levels in healthy subjects. Clin Pharmacol Ther. 1999 Oct;66(4):408-14.
5 The contribution of the enzymes CYP2D6 and CYP2C19 in the demethylation of artemether in healthy subjects. Eur J Drug Metab Pharmacokinet. 1998 Jul-Sep;23(3):429-36.
6 Effect of pharmacogenetics on plasma lumefantrine pharmacokinetics and malaria treatment outcome in pregnant women. Malar J. 2017 Jul 3;16(1):267.
7 Pharmacokinetic interaction between etravirine or darunavir/ritonavir and artemether/lumefantrine in healthy volunteers: a two-panel, two-way, two-period, randomized trial. HIV Med. 2013 Aug;14(7):421-9.
8 Insights into CYP2B6-mediated drug-drug interactions. Acta Pharm Sin B. 2016 Sep;6(5):413-425.
9 Fetal bovine serum and human constitutive androstane receptor: evidence for activation of the SV23 splice variant by artemisinin, artemether, and arteether in a serum-free cell culture system. Toxicol Appl Pharmacol. 2014 Jun 1;277(2):221-30. doi: 10.1016/j.taap.2014.03.023. Epub 2014 Apr 12.
10 Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem J. 2000 Oct 1;351(Pt 1):95-105.
11 Synthesis and structure-activity relationships of pyrazolodiazepine derivatives as human P2X7 receptor antagonists. Bioorg Med Chem Lett. 2009 Nov 1;19(21):6053-8.
12 CaMKII regulates retinoic acid receptor transcriptional activity and the differentiation of myeloid leukemia cells. J Clin Invest. 2007 May;117(5):1412-21. doi: 10.1172/JCI30779. Epub 2007 Apr 12.