General Information of Drug Combination (ID: DC2RXM4)

Drug Combination Name
KN-62 Primaquine
Indication
Disease Entry Status REF
DD2 Investigative [1]
Component Drugs KN-62   DMLZ89P Primaquine   DMWQ16I
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: 10.28
Bliss Independence Score: 12.164
Loewe Additivity Score: 7.845
LHighest Single Agent (HSA) Score: 10.301

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 Primaquine
Disease Entry ICD 11 Status REF
Malaria 1F40-1F45 Approved [3]
Primaquine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Plasmodium Deoxyribonucleic acid (Malaria DNA) TT698WO NOUNIPROTAC . [7]
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Primaquine Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [8]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [9]
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Primaquine Interacts with 17 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 1A2 (CYP1A2) OTLLBX48 CP1A2_HUMAN Increases Expression [10]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Increases Expression [10]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Increases Expression [11]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [12]
Proepiregulin (EREG) OTRM4NQY EREG_HUMAN Increases Expression [13]
Interleukin-1 alpha (IL1A) OTPSGILV IL1A_HUMAN Decreases Expression [13]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Decreases Expression [13]
Antileukoproteinase (SLPI) OTUNFUU8 SLPI_HUMAN Increases Expression [13]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Expression [13]
Tissue factor (F3) OT3MSU3B TF_HUMAN Increases Expression [14]
Phosphatidylcholine translocator ABCB4 (ABCB4) OTE6PY83 MDR3_HUMAN Decreases Activity [15]
Hemoglobin subunit gamma-2 (HBG2) OT4J48JJ HBG2_HUMAN Increases Expression [16]
Interleukin-24 (IL24) OT4VUWH1 IL24_HUMAN Decreases Expression [13]
Glucose-6-phosphate 1-dehydrogenase (G6PD) OT300SMK G6PD_HUMAN Decreases Response To Substance [17]
Cytochrome P450 2E1 (CYP2E1) OTHQ17JG CP2E1_HUMAN Increases Metabolism [16]
Cytochrome P450 2B6 (CYP2B6) OTOYO4S7 CP2B6_HUMAN Increases Metabolism [16]
Cytochrome P450 2D6 (CYP2D6) OTZJC802 CP2D6_HUMAN Increases Metabolism [16]
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⏷ Show the Full List of 17 DOT(s)

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 FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 008316.
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 Primaquine-induced differential gene expression analysis in mice liver using DNA microarrays. Toxicology. 2007 Sep 24;239(1-2):96-107.
8 Primaquine metabolism by human liver microsomes: effect of other antimalarial drugs. Biochem Pharmacol. 1992 Aug 4;44(3):587-90.
9 Identification of human cytochrome P(450)s that metabolise anti-parasitic drugs and predictions of in vivo drug hepatic clearance from in vitro data. Eur J Clin Pharmacol. 2003 Sep;59(5-6):429-42.
10 Cytochrome P450 1A1/2 induction by antiparasitic drugs: dose-dependent increase in ethoxyresorufin O-deethylase activity and mRNA caused by quinine, primaquine and albendazole in HepG2 cells. Eur J Clin Pharmacol. 2002 Nov;58(8):537-42.
11 Time-dependent transcriptional induction of CYP1A1, CYP1A2 and CYP1B1 mRNAs by H+/K+ -ATPase inhibitors and other xenobiotics. Xenobiotica. 2003 Feb;33(2):107-18.
12 Interference with bile salt export pump function is a susceptibility factor for human liver injury in drug development. Toxicol Sci. 2010 Dec; 118(2):485-500.
13 An in vitro coculture system of human peripheral blood mononuclear cells with hepatocellular carcinoma-derived cells for predicting drug-induced liver injury. Arch Toxicol. 2021 Jan;95(1):149-168. doi: 10.1007/s00204-020-02882-4. Epub 2020 Aug 20.
14 Elucidating mechanisms of toxicity using phenotypic data from primary human cell systems--a chemical biology approach for thrombosis-related side effects. Int J Mol Sci. 2015 Jan 5;16(1):1008-29. doi: 10.3390/ijms16011008.
15 Evaluating the Role of Multidrug Resistance Protein 3 (MDR3) Inhibition in Predicting Drug-Induced Liver Injury Using 125 Pharmaceuticals. Chem Res Toxicol. 2017 May 15;30(5):1219-1229. doi: 10.1021/acs.chemrestox.7b00048. Epub 2017 May 4.
16 Cytochrome P(450)-dependent toxic effects of primaquine on human erythrocytes. Toxicol Appl Pharmacol. 2009 Nov 15;241(1):14-22. doi: 10.1016/j.taap.2009.07.012. Epub 2009 Jul 17.
17 Understanding the mechanisms for metabolism-linked hemolytic toxicity of primaquine against glucose 6-phosphate dehydrogenase deficient human erythrocytes: evaluation of eryptotic pathway. Toxicology. 2012 Mar 29;294(1):54-60. doi: 10.1016/j.tox.2012.01.015. Epub 2012 Feb 6.