Details of the Drug Combination

General Information of Drug Combination (ID: DCJR6WL)

Drug Combination Name

KN-62 Methylene blue

Indication

Disease Entry	Status	REF
DD2	Investigative	[1]

Component Drugs

KN-62 DMLZ89P

Methylene blue DMJAPE7

Small molecular drug

N.A.

2D MOL

3D MOL is unavailable

3D MOL

High-throughput Screening Result

Testing Cell Line: DD2

Zero Interaction Potency (ZIP) Score: 21.983

Bliss Independence Score: 20.903

Loewe Additivity Score: 12.094

LHighest Single Agent (HSA) Score: 21.259

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	[5]
Protein kinase C alpha (PRKCA)	TTFJ8Q1	KPCA_HUMAN	Inhibitor	[5]
Stress-activated protein kinase JNK1 (JNK1)	TT0K6EO	MK08_HUMAN	Inhibitor	[5]
Rho-associated protein kinase 1 (ROCK1)	TTZN7RP	ROCK1_HUMAN	Inhibitor	[5]
Stress-activated protein kinase 2b (p38 beta)	TT73U6C	MK11_HUMAN	Inhibitor	[5]
Extracellular signal-regulated kinase 2 (ERK2)	TT4TQBX	MK01_HUMAN	Inhibitor	[5]
Checkpoint kinase-1 (CHK1)	TTTU902	CHK1_HUMAN	Inhibitor	[5]
P2X purinoceptor 7 (P2RX7)	TT473XN	P2RX7_HUMAN	Inhibitor	[6]
Serine/threonine-protein kinase Sgk1 (SGK1)	TTTV8EJ	SGK1_HUMAN	Inhibitor	[5]
Stress-activated protein kinase 2a (p38 alpha)	TTQBR95	MK14_HUMAN	Inhibitor	[5]
RAC-alpha serine/threonine-protein kinase (AKT1)	TTWTSCV	AKT1_HUMAN	Inhibitor	[5]
MAP kinase p38 (MAPK12)	TTYT93M	MK12_HUMAN	Inhibitor	[5]
Ribosomal protein S6 kinase beta-1 (S6K1)	TTG0U4H	KS6B1_HUMAN	Inhibitor	[5]
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⏷ Show the Full List of 13 DTT(s)

Indication(s) of Methylene blue

Disease Entry	ICD 11	Status	REF
Acquired methemoglobinemia	3A93	Approved	[3]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 2	[4]

Methylene blue Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Monoamine oxidase (MAO)	TT32XQJ	NOUNIPROTAC	.	[7]
Guanylate cyclase (GC)	TT6HPVC	NOUNIPROTAC	Inhibitor	[8]
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Methylene blue Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
6-phosphogluconate dehydrogenase, decarboxylating (PGD)	OTVG296F	6PGD_HUMAN	Increases Activity	[9]
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Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Hepatoblastoma	DC6N1D6	HB3	Investigative	[10]
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References

1	CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
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	Recombinant Plasmodium falciparum glutathione reductase is inhibited by the antimalarial dye methylene blue. FEBS Lett. 1998 Feb 6;422(3):311-4.
4	ClinicalTrials.gov (NCT04370288) Clinical Application of Methylene Blue for Treatment of Covid-19 Patients. U.S. National Institutes of Health.
5	Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem J. 2000 Oct 1;351(Pt 1):95-105.
6	Synthesis and structure-activity relationships of pyrazolodiazepine derivatives as human P2X7 receptor antagonists. Bioorg Med Chem Lett. 2009 Nov 1;19(21):6053-8.
7	Photoluminescence of CdTe nanocrystals modulated by methylene blue and DNA. A label-free luminescent signaling nanohybrid platform. Phys Chem Chem Phys. 2009 Jul 7;11(25):5062-9.
8	Curcumin ameliorates high glucose-induced acute vascular endothelial dysfunction in rat thoracic aorta. Clin Exp Pharmacol Physiol. 2009 Dec;36(12):1177-82.
9	Defenses against oxidation in human erythrocytes: role of glutathione reductase in the activation of glucose decarboxylation by hemolytic drugs. J Lab Clin Med. 1991 Apr;117(4):325-31.
10	CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125976