Details of the Drug Combination

General Information of Drug Combination (ID: DCRM15J)

Drug Combination Name
KN-62 Lumefantrine
Indication
Disease Entry Status REF
DD2 Investigative [1]
Component Drugs KN-62   DMLZ89P Lumefantrine   DM29GAD
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL is unavailable 3D MOL
High-throughput Screening Result Testing Cell Line: DD2
Zero Interaction Potency (ZIP) Score: 7.969
Bliss Independence Score: 7.324
Loewe Additivity Score: 4.341
LHighest Single Agent (HSA) Score: 8.858

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of KN-62
Disease Entry ICD 11 Status REF
Discovery agent N.A. Investigative [2]
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 [4]
Protein kinase C alpha (PRKCA) TTFJ8Q1 KPCA_HUMAN Inhibitor [4]
Stress-activated protein kinase JNK1 (JNK1) TT0K6EO MK08_HUMAN Inhibitor [4]
Rho-associated protein kinase 1 (ROCK1) TTZN7RP ROCK1_HUMAN Inhibitor [4]
Stress-activated protein kinase 2b (p38 beta) TT73U6C MK11_HUMAN Inhibitor [4]
Extracellular signal-regulated kinase 2 (ERK2) TT4TQBX MK01_HUMAN Inhibitor [4]
Checkpoint kinase-1 (CHK1) TTTU902 CHK1_HUMAN Inhibitor [4]
P2X purinoceptor 7 (P2RX7) TT473XN P2RX7_HUMAN Inhibitor [5]
Serine/threonine-protein kinase Sgk1 (SGK1) TTTV8EJ SGK1_HUMAN Inhibitor [4]
Stress-activated protein kinase 2a (p38 alpha) TTQBR95 MK14_HUMAN Inhibitor [4]
RAC-alpha serine/threonine-protein kinase (AKT1) TTWTSCV AKT1_HUMAN Inhibitor [4]
MAP kinase p38 (MAPK12) TTYT93M MK12_HUMAN Inhibitor [4]
Ribosomal protein S6 kinase beta-1 (S6K1) TTG0U4H KS6B1_HUMAN Inhibitor [4]
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⏷ 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 [4]
Glycogen synthase kinase-3 beta (GSK3B) OTL3L14B GSK3B_HUMAN Decreases Activity [4]
MAP kinase-activated protein kinase 5 (MAPKAPK5) OTAZHPVK MAPK5_HUMAN Decreases Activity [4]
Integrin alpha-M (ITGAM) OTAG6HWU ITAM_HUMAN Increases Expression [6]
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Indication(s) of Lumefantrine
Disease Entry ICD 11 Status REF
Malaria 1F40-1F45 Approved [3]
Lumefantrine 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 [7]
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Lumefantrine Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [8]
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Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Hepatoblastoma DCX2TA2 HB3 Investigative [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 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).
3 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
4 Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem J. 2000 Oct 1;351(Pt 1):95-105.
5 Synthesis and structure-activity relationships of pyrazolodiazepine derivatives as human P2X7 receptor antagonists. Bioorg Med Chem Lett. 2009 Nov 1;19(21):6053-8.
6 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.
7 The fight against drug-resistant malaria: novel plasmodial targets and antimalarial drugs. Curr Med Chem. 2008;15(2):161-71.
8 Development of a paediatric physiologically based pharmacokinetic model to assess the impact of drug-drug interactions in tuberculosis co-infected malaria subjects: A case study with artemether-lumefantrine and the CYP3A4-inducer rifampicin. Eur J Pharm Sci. 2017 Aug 30;106:20-33.
9 Loss of function mutations in VARS encoding cytoplasmic valyl-tRNA synthetase cause microcephaly, seizures, and progressive cerebral atrophy.Hum Genet. 2018 Apr;137(4):293-303. doi: 10.1007/s00439-018-1882-3. Epub 2018 Apr 24.