Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTME0KO7)

• DOT Name: Creatine kinase M-type (CKM)
• Synonyms: EC 2.7.3.2; Creatine kinase M chain; Creatine phosphokinase M-type; CPK-M; M-CK
• Gene Name: CKM
• Related Disease:
  Type-1/2 diabetes
  Chronic kidney disease
  Colon cancer
  Colonic neoplasm
  Myocardial infarction
  Non-insulin dependent diabetes
  Qualitative or quantitative defects of dysferlin
  Acute coronary syndrome
  Ischemia
  Myotonic dystrophy
  Myotonic dystrophy type 1
• UniProt ID: KCRM_HUMAN
• PDB ID: 1I0E; 7BF2
• EC Number: 2.7.3.2
• Pfam ID: PF00217 ; PF02807
• Sequence:
  MPFGNTHNKFKLNYKPEEEYPDLSKHNNHMAKVLTLELYKKLRDKETPSGFTVDDVIQTG
  VDNPGHPFIMTVGCVAGDEESYEVFKELFDPIISDRHGGYKPTDKHKTDLNHENLKGGDD
  LDPNYVLSSRVRTGRSIKGYTLPPHCSRGERRAVEKLSVEALNSLTGEFKGKYYPLKSMT
  EKEQQQLIDDHFLFDKPVSPLLLASGMARDWPDARGIWHNDNKSFLVWVNEEDHLRVISM
  EKGGNMKEVFRRFCVGLQKIEEIFKKAGHPFMWNQHLGYVLTCPSNLGTGLRGGVHVKLA
  HLSKHPKFEEILTRLRLQKRGTGGVDTAAVGSVFDVSNADRLGSSEVEQVQLVVDGVKLM
  VEMEKKLEKGQSIDDMIPAQK
• Function: Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate). Creatine kinase isoenzymes play a central role in energy transduction in tissues with large, fluctuating energy demands, such as skeletal muscle, heart, brain and spermatozoa.
• KEGG Pathway:
  Arginine and proline metabolism (hsa00330)
  Metabolic pathways (hsa01100)
  Cytoskeleton in muscle cells (hsa04820)
• Reactome Pathway: Creatine metabolism (R-HSA-71288)
• BioCyc Pathway: MetaCyc:HS02640-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Type-1/2 diabetes	DISIUHAP	Definitive	Biomarker	[1]
Chronic kidney disease	DISW82R7	Strong	Biomarker	[2]
Colon cancer	DISVC52G	Strong	Biomarker	[3]
Colonic neoplasm	DISSZ04P	Strong	Biomarker	[3]
Myocardial infarction	DIS655KI	Strong	Biomarker	[4]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[5]
Qualitative or quantitative defects of dysferlin	DIS59VEJ	Strong	Biomarker	[6]
Acute coronary syndrome	DIS7DYEW	Limited	Biomarker	[7]
Ischemia	DIS5XOOY	Limited	Biomarker	[8]
Myotonic dystrophy	DISNBEMX	Limited	Genetic Variation	[9]
Myotonic dystrophy type 1	DISJC0OX	Limited	Genetic Variation	[10]

13 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Creatine kinase M-type (CKM).	[11]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Creatine kinase M-type (CKM).	[12]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Creatine kinase M-type (CKM).	[13]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Creatine kinase M-type (CKM).	[14]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Creatine kinase M-type (CKM).	[15]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of Creatine kinase M-type (CKM).	[16]
Etoposide	DMNH3PG	Approved	Etoposide decreases the expression of Creatine kinase M-type (CKM).	[17]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of Creatine kinase M-type (CKM).	[18]
Mitoxantrone	DMM39BF	Approved	Mitoxantrone decreases the expression of Creatine kinase M-type (CKM).	[12]
Daunorubicin	DMQUSBT	Approved	Daunorubicin decreases the expression of Creatine kinase M-type (CKM).	[12]
Phenytoin	DMNOKBV	Approved	Phenytoin increases the expression of Creatine kinase M-type (CKM).	[19]
Carbimazole	DMULAI4	Approved	Carbimazole increases the expression of Creatine kinase M-type (CKM).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Creatine kinase M-type (CKM).	[23]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Salbutamol	DMN9CWF	Approved	Salbutamol increases the secretion of Creatine kinase M-type (CKM).	[20]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Creatine kinase M-type (CKM).	[22]

References

• [1] Relation of Chronic Total Occlusion to In-Hospital Mortality in the Patients With Sudden Cardiac Arrest Due to Acute Coronary Syndrome.Am J Cardiol. 2019 Jun 15;123(12):1915-1920. doi: 10.1016/j.amjcard.2019.02.059. Epub 2019 Mar 16.
• [2] Role of Cardio-Specific Micro-RibonucleicAcids and Correlation with Cardiac Biomarkers in Acute Coronary Syndrome: A Comprehensive Systematic Review.Cureus. 2019 Oct 9;11(10):e5878. doi: 10.7759/cureus.5878.
• [3] Global gene expression analysis of rat colon cancers induced by a food-borne carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine.Carcinogenesis. 2004 Aug;25(8):1495-505. doi: 10.1093/carcin/bgh155. Epub 2004 Apr 1.
• [4] Role of JNK signalling pathway and plateletlymphocyte aggregates in myocardial ischemiareperfusion injury and the cardioprotective effect of ischemic postconditioning in rats.Mol Med Rep. 2018 Dec;18(6):5237-5242. doi: 10.3892/mmr.2018.9545. Epub 2018 Oct 10.
• [5] Creatine kinase muscle type specifically interacts with saturated fatty acid- and/or monounsaturated fatty acid-containing phosphatidic acids.Biochem Biophys Res Commun. 2019 Jun 11;513(4):1035-1040. doi: 10.1016/j.bbrc.2019.04.097. Epub 2019 Apr 19.
• [6] Proteomic analysis of the skeletal muscles from dysferlinopathy patients.J Clin Neurosci. 2020 Jan;71:186-190. doi: 10.1016/j.jocn.2019.08.068. Epub 2019 Aug 19.
• [7] The relationship between trace elements and cardiac markers in acute coronary syndromes.J Trace Elem Med Biol. 2005;18(3):235-42. doi: 10.1016/j.jtemb.2004.12.002.
• [8] N-acetylcysteine and allopurinol synergistically enhance cardiac adiponectin content and reduce myocardial reperfusion injury in diabetic rats.PLoS One. 2011;6(8):e23967. doi: 10.1371/journal.pone.0023967. Epub 2011 Aug 30.
• [9] The 1.5-Mb region spanning the myotonic dystrophy locus shows uniform recombination frequency.Am J Hum Genet. 1994 Jan;54(1):104-13.
• [10] Linkage disequilibrium detected between dystrophia myotonica and APOC2 locus in the Finnish population.Hum Genet. 1990 Oct;85(5):541-5. doi: 10.1007/BF00194234.
• [11] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [12] Identification of genomic biomarkers for anthracycline-induced cardiotoxicity in human iPSC-derived cardiomyocytes: an in vitro repeated exposure toxicity approach for safety assessment. Arch Toxicol. 2016 Nov;90(11):2763-2777.
• [13] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [14] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [15] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [16] [Muscular damage during isotretinoin treatment]. Ann Dermatol Venereol. 1998 Feb;125(2):94-7.
• [17] Cell death mechanisms of the anti-cancer drug etoposide on human cardiomyocytes isolated from pluripotent stem cells. Arch Toxicol. 2018 Apr;92(4):1507-1524.
• [18] Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
• [19] Myopathy and hypersensitivity to phenytoin. Neurology. 1983 Jun;33(6):790-1. doi: 10.1212/wnl.33.6.790.
• [20] Elevation of creatine kinase from skeletal muscle associated with inhaled albuterol. Ann Allergy Asthma Immunol. 1996 Dec;77(6):488-90. doi: 10.1016/S1081-1206(10)63356-X.
• [21] Myositis in association with carbimazole therapy. Lancet. 1989 Apr 29;1(8644):964. doi: 10.1016/s0140-6736(89)92550-6.
• [22] 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.
• [23] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.