Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMPTMKH)

• Drug Name: KN-93 Drug Info
• Synonyms: kn-93; 139298-40-1; KN 93; KN93; Methoxybenzene-sulfonamide; C26H29ClN2O4S; CHEMBL155333; (E)-N-(2-(((3-(4-Chlorophenyl)allyl)(methyl)amino)methyl)phenyl)-N-(2-hydroxyethyl)-4-methoxybenzenesulfonamide; 2-(N-(2-Hydroxyethyl)-N-(4-methoxybenzenesulfonyl))amino-N-(4-chlorocinnamyl)-N-methylbenzylamine; N-(2-(((3-(4-Chlorophenyl)-2-propenyl)methylamino)methyl)phenyl)-N-(2-hydroxyethyl)-4-methoxybenzenesulfonamide; Benzenesulfonamide, N-(2-(((3-(4-chlorophenyl)-2-propenyl)methylamino)methyl)ph

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 5312122
  ChEBI ID: CHEMBL91460
  CAS Number: CAS 139298-40-1
  TTD Drug ID: DMPTMKH

Molecule-Related Drug Atlas

Drug(s) Targeting CaM-kinase II (CAMK2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Rimacalib	DMSC7TN	Rheumatoid arthritis	FA20	Phase 2	[5]
ABIO 09-01	DM0LUOM	Anxiety disorder	6B00-6B0Z	Investigative	[6]
PMID18337095C27	DMEOHLV	Discovery agent	N.A.	Investigative	[7]
PMID18334293C15b	DM1I6AY	Discovery agent	N.A.	Investigative	[8]

Drug(s) Affected By Retinoblastoma-associated protein (RB1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Indomethacin	DMSC4A7	Bursitis		Approved	[9]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[10]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[11]
Talazoparib	DM1KS78	Breast cancer	2C60-2C65	Approved	[12]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[13]
Trametinib	DM2JGQ3	Melanoma	2C30	Approved	[14]
Sulindac	DM2QHZU	Acute myelogenous leukaemia	2A41	Approved	[15]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[16]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[17]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[18]

Drug(s) Affected By Calcium/calmodulin-dependent protein kinase type 1 (CAMK1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Quercetin	DM3NC4M	Obesity	5B81	Approved	[19]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[20]
Ivermectin	DMDBX5F	Intestinal strongyloidiasis due to nematode parasite	1F6B	Approved	[21]
Cupric Sulfate	DMP0NFQ	Fungal infection	1F29-1F2F	Approved	[22]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[23]
Topotecan	DMP6G8T	Central nervous system neoplasm		Approved	[24]
Tamibarotene	DM3G74J	T-cell leukaemia	2A90	Phase 3	[20]
phorbol 12-myristate 13-acetate	DMJWD62	Acute myeloid leukaemia	2A60	Phase 2	[25]
Afimoxifene	DMFORDT	Breast cancer	2C60-2C65	Phase 2	[26]
Benzo(a)pyrene	DMN7J43	N. A.	N. A.	Phase 1	[27]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
CaM-kinase II (CAMK2)	TTFYL58	KCC2A_HUMAN; KCC2B_HUMAN; KCC2D_HUMAN; KCC2G_HUMAN	Inhibitor	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Calcium/calmodulin-dependent protein kinase type 1 (CAMK1)	OTRN55RE	KCC1A_HUMAN	Gene/Protein Processing	[3]
Retinoblastoma-associated protein (RB1)	OTQJUJMZ	RB_HUMAN	Post-Translational Modifications	[4]

References

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• [2] Discovery of a 3-amino-6-phenyl-pyridazine derivative as a new synthetic antineuroinflammatory compound. J Med Chem. 2002 Jan 31;45(3):563-6.
• [3] Calmodulin-dependent kinase I regulates adrenal cell expression of aldosterone synthase. Endocrinology. 2002 Sep;143(9):3651-7. doi: 10.1210/en.2001-211359.
• [4] Calcium/calmodulin-dependent kinase I and calcium/calmodulin-dependent kinase kinase participate in the control of cell cycle progression in MCF-7 human breast cancer cells. Cancer Res. 2005 Jun 15;65(12):5408-16. doi: 10.1158/0008-5472.CAN-05-0271.
• [5] Role for CaMKII inhibition in rheumatoid arthritis: effects on HIF-1-induced VEGF production by rheumatoid synovial fibroblasts. Ann N Y Acad Sci. 2009 Sep;1173:706-11.
• [6] 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. (Target id: 1558).
• [7] Aryl-indolyl maleimides as inhibitors of CaMKIIdelta. Part 3: Importance of the indole orientation. Bioorg Med Chem Lett. 2008 Apr 1;18(7):2399-403.
• [8] Pyrimidine-based inhibitors of CaMKIIdelta. Bioorg Med Chem Lett. 2008 Apr 1;18(7):2404-8.
• [9] Indomethacin inhibits cell growth of medullary thyroid carcinoma by reducing cell cycle progression into S phase. Exp Biol Med (Maywood). 2008 Nov;233(11):1433-40. doi: 10.3181/0804-RM-127. Epub 2008 Sep 12.
• [10] Therapeutically activating RB: reestablishing cell cycle control in endocrine therapy-resistant breast cancer. Endocr Relat Cancer. 2011 Apr 28;18(3):333-45. doi: 10.1530/ERC-10-0262. Print 2011 Jun.
• [11] Effects and mechanisms of betulinic acid on improving EGFR TKI-resistance of lung cancer cells. Environ Toxicol. 2018 Nov;33(11):1153-1159.
• [12] BMN 673 (talazoparib): A potent PARP inhibitor for triple negative breast cancer with different genetic profile. J Biochem Mol Toxicol. 2019 May;33(5):e22286. doi: 10.1002/jbt.22286. Epub 2019 Jan 23.
• [13] Microarray analysis of H2O2-, HNE-, or tBH-treated ARPE-19 cells. Free Radic Biol Med. 2002 Nov 15;33(10):1419-32.
• [14] Combination small molecule MEK and PI3K inhibition enhances uveal melanoma cell death in a mutant GNAQ- and GNA11-dependent manner. Clin Cancer Res. 2012 Aug 15;18(16):4345-55. doi: 10.1158/1078-0432.CCR-11-3227. Epub 2012 Jun 25.
• [15] Sulindac induces specific degradation of the HPV oncoprotein E7 and causes growth arrest and apoptosis in cervical carcinoma cells. Cancer Lett. 2007 Jan 8;245(1-2):103-11. doi: 10.1016/j.canlet.2005.12.034. Epub 2006 Feb 20.
• [16] Melanoma coordinates general and cell-specific mechanisms to promote methotrexate resistance. Exp Cell Res. 2012 Jun 10;318(10):1146-59.
• [17] HMG-CoA reductase inhibitor simvastatin inhibits cell cycle progression at the G1/S checkpoint in immortalized lymphocytes from Alzheimer's disease patients independently of cholesterol-lowering effects. J Pharmacol Exp Ther. 2008 Jan;324(1):352-9. doi: 10.1124/jpet.107.128959. Epub 2007 Oct 10.
• [18] Inhibition of prostate cancer cell colony formation by the flavonoid quercetin correlates with modulation of specific regulatory genes. Clin Diagn Lab Immunol. 2004 Jan;11(1):63-9. doi: 10.1128/cdli.11.1.63-69.2004.
• [19] Integrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer-related mechanisms in colon cancer cells in vitro. Eur J Nutr. 2005 Mar;44(3):143-56. doi: 10.1007/s00394-004-0503-1. Epub 2004 Apr 30.
• [20] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [21] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [22] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [23] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [24] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.
• [25] Metformin blocks migration and invasion of tumour cells by inhibition of matrix metalloproteinase-9 activation through a calcium and protein kinase Calpha-dependent pathway: phorbol-12-myristate-13-acetate-induced/extracellular signal-regulated kinase/activator protein-1. Br J Pharmacol. 2010 Jul;160(5):1195-211. doi: 10.1111/j.1476-5381.2010.00762.x.
• [26] High-throughput ectopic expression screen for tamoxifen resistance identifies an atypical kinase that blocks autophagy. Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):2058-63.
• [27] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.