Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT65E12V)

• DOT Name: Troponin I, cardiac muscle (TNNI3)
• Synonyms: Cardiac troponin I
• Gene Name: TNNI3
• Related Disease:
  Dilated cardiomyopathy 2A
  Hypertrophic cardiomyopathy
  Hypertrophic cardiomyopathy 7
  Cardiomyopathy, familial restrictive, 1
  Dilated cardiomyopathy 1FF
  Dilated cardiomyopathy
  Obsolete familial isolated dilated cardiomyopathy
  Obsolete familial isolated restrictive cardiomyopathy
  Arrhythmogenic right ventricular cardiomyopathy
• UniProt ID: TNNI3_HUMAN
• PDB ID: 1J1D; 1J1E; 1LXF; 1MXL; 1OZS; 2KGB; 2KRD; 2L1R; 2MZP; 2N7L; 4Y99; 5VLN; 5W88; 5WCL; 6KN7; 6KN8; 6MV3; 7JGI; 7SC2; 7SC3; 7SUP; 7SVC; 7SWG; 7SWI; 7SXC; 7SXD; 7UH9; 7UHA; 7UTI; 7UTL; 8DZV
• Pfam ID: PF00992 ; PF11636
• Sequence:
  MADGSSDAAREPRPAPAPIRRRSSNYRAYATEPHAKKKSKISASRKLQLKTLLLQIAKQE
  LEREAEERRGEKGRALSTRCQPLELAGLGFAELQDLCRQLHARVDKVDEERYDIEAKVTK
  NITEIADLTQKIFDLRGKFKRPTLRRVRISADAMMQALLGARAKESLDLRAHLKQVKKED
  TEKENREVGDWRKNIDALSGMEGRKKKFES
• Function: Troponin I is the inhibitory subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity.
• KEGG Pathway:
  cAMP sig.ling pathway (hsa04024)
  Cardiac muscle contraction (hsa04260)
  Adrenergic sig.ling in cardiomyocytes (hsa04261)
  Motor proteins (hsa04814)
  Cytoskeleton in muscle cells (hsa04820)
  Hypertrophic cardiomyopathy (hsa05410)
  Dilated cardiomyopathy (hsa05414)
  Diabetic cardiomyopathy (hsa05415)
• Reactome Pathway:
  Ion homeostasis (R-HSA-5578775)
  Striated Muscle Contraction (R-HSA-390522)

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Dilated cardiomyopathy 2A	DIS2CICC	Definitive	Autosomal recessive	[1]
Hypertrophic cardiomyopathy	DISQG2AI	Definitive	Autosomal dominant	[2]
Hypertrophic cardiomyopathy 7	DIS7649X	Definitive	Autosomal dominant	[3]
Cardiomyopathy, familial restrictive, 1	DIS4AJ17	Strong	Autosomal dominant	[4]
Dilated cardiomyopathy 1FF	DISYUFV5	Strong	Autosomal dominant	[5]
Dilated cardiomyopathy	DISX608J	Moderate	Autosomal dominant	[2]
Obsolete familial isolated dilated cardiomyopathy	DIS4FXO4	Supportive	Autosomal dominant	[6]
Obsolete familial isolated restrictive cardiomyopathy	DIS51KNV	Supportive	Autosomal dominant	[4]
Arrhythmogenic right ventricular cardiomyopathy	DIS3V2BE	No Known	Autosomal dominant	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Troponin I, cardiac muscle (TNNI3).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Troponin I, cardiac muscle (TNNI3).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Troponin I, cardiac muscle (TNNI3).	[9]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Troponin I, cardiac muscle (TNNI3).	[10]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Troponin I, cardiac muscle (TNNI3).	[11]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Troponin I, cardiac muscle (TNNI3).	[12]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Troponin I, cardiac muscle (TNNI3).	[13]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Troponin I, cardiac muscle (TNNI3).	[14]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Troponin I, cardiac muscle (TNNI3).	[15]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Troponin I, cardiac muscle (TNNI3).	[16]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Troponin I, cardiac muscle (TNNI3).	[17]
Melphalan	DMOLNHF	Approved	Melphalan increases the expression of Troponin I, cardiac muscle (TNNI3).	[19]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide increases the expression of Troponin I, cardiac muscle (TNNI3).	[20]
Methamphetamine	DMPM4SK	Approved	Methamphetamine increases the expression of Troponin I, cardiac muscle (TNNI3).	[21]
Perphenazine	DMA4MRX	Approved	Perphenazine increases the expression of Troponin I, cardiac muscle (TNNI3).	[22]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Troponin I, cardiac muscle (TNNI3).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Troponin I, cardiac muscle (TNNI3).	[23]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Troponin I, cardiac muscle (TNNI3).	[24]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Troponin I, cardiac muscle (TNNI3).	[26]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Troponin I, cardiac muscle (TNNI3).	[27]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Troponin I, cardiac muscle (TNNI3).	[28]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Troponin I, cardiac muscle (TNNI3).	[29]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cocaine	DMSOX7I	Approved	Cocaine increases the secretion of Troponin I, cardiac muscle (TNNI3).	[18]
PMID25656651-Compound-5	DMAI95U	Patented	PMID25656651-Compound-5 increases the secretion of Troponin I, cardiac muscle (TNNI3).	[25]

References

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• [3] Thin filament mutations: developing an integrative approach to a complex disorder. Circ Res. 2011 Mar 18;108(6):765-82. doi: 10.1161/CIRCRESAHA.110.224170.
• [4] Idiopathic restrictive cardiomyopathy is part of the clinical expression of cardiac troponin I mutations. J Clin Invest. 2003 Jan;111(2):209-16. doi: 10.1172/JCI16336.
• [5] Transgenic modeling of a cardiac troponin I mutation linked to familial hypertrophic cardiomyopathy. Circ Res. 2000 Oct 27;87(9):805-11. doi: 10.1161/01.res.87.9.805.
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• [17] Expression profile analysis of colon cancer cells in response to sulindac or aspirin. Biochem Biophys Res Commun. 2002 Mar 29;292(2):498-512.
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• [19] Cardiac toxicity of high-dose cyclophosphamide and melphalan in patients with multiple myeloma treated with tandem autologous hematopoietic stem cell transplantation. Int J Hematol. 2008 Sep;88(2):227-236. doi: 10.1007/s12185-008-0112-5. Epub 2008 Jun 12.
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• [21] Methamphetamine-induced myocardial infarction with elevated troponin I. Am J Emerg Med. 2006 Jan;24(1):132-4. doi: 10.1016/j.ajem.2005.08.005.
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• [29] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.