Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNG0L8J)

• DOT Name: Heat shock protein 75 kDa, mitochondrial (TRAP1)
• Synonyms: HSP 75; TNFR-associated protein 1; Tumor necrosis factor type 1 receptor-associated protein; TRAP-1
• Gene Name: TRAP1
• Related Disease:
  Adenocarcinoma
  Adult glioblastoma
  Anaplastic large cell lymphoma
  Breast carcinoma
  Breast neoplasm
  Carcinoma of esophagus
  Colitis
  Colorectal carcinoma
  Colorectal neoplasm
  Congenital anomaly of kidney and urinary tract
  Crohn disease
  Esophageal cancer
  Esophageal squamous cell carcinoma
  Gastric cancer
  Gastric neoplasm
  Glioblastoma multiforme
  Glioma
  Hereditary diffuse gastric adenocarcinoma
  Late-onset Parkinson disease
  Lung cancer
  Lung carcinoma
  Malignant glioma
  Metastatic malignant neoplasm
  Metastatic prostate carcinoma
  Neoplasm of esophagus
  Nephropathy
  Non-small-cell lung cancer
  Paraganglioma
  Parkinson disease
  Renal fibrosis
  Systemic lupus erythematosus
  Thyroid gland carcinoma
  VACTERL/vater association
  Carcinoma
  Colon cancer
  Kidney cancer
  Lupus nephritis
  Nephritis
  Prostate cancer
  Prostate carcinoma
  Breast cancer
  Carcinoma of liver and intrahepatic biliary tract
  Hepatitis B virus infection
  Liver cancer
  Neuroblastoma
  Osteoarthritis
• UniProt ID: TRAP1_HUMAN
• PDB ID: 4Z1F; 4Z1G; 4Z1H; 4Z1I; 5F3K; 5F5R; 5HPH; 5Y3N; 5Y3O; 6XG6; 7C04; 7C05; 7C7B; 7C7C; 7KCK; 7KCL; 7KCM; 7KLU; 7KLV; 7U8U; 7U8V; 7U8W; 7U8X; 7ULK
• Pfam ID: PF13589 ; PF00183
• Sequence:
  MARELRALLLWGRRLRPLLRAPALAAVPGGKPILCPRRTTAQLGPRRNPAWSLQAGRLFS
  TQTAEDKEEPLHSIISSTESVQGSTSKHEFQAETKKLLDIVARSLYSEKEVFIRELISNA
  SDALEKLRHKLVSDGQALPEMEIHLQTNAEKGTITIQDTGIGMTQEELVSNLGTIARSGS
  KAFLDALQNQAEASSKIIGQFGVGFYSAFMVADRVEVYSRSAAPGSLGYQWLSDGSGVFE
  IAEASGVRTGTKIIIHLKSDCKEFSSEARVRDVVTKYSNFVSFPLYLNGRRMNTLQAIWM
  MDPKDVREWQHEEFYRYVAQAHDKPRYTLHYKTDAPLNIRSIFYVPDMKPSMFDVSRELG
  SSVALYSRKVLIQTKATDILPKWLRFIRGVVDSEDIPLNLSRELLQESALIRKLRDVLQQ
  RLIKFFIDQSKKDAEKYAKFFEDYGLFMREGIVTATEQEVKEDIAKLLRYESSALPSGQL
  TSLSEYASRMRAGTRNIYYLCAPNRHLAEHSPYYEAMKKKDTEVLFCFEQFDELTLLHLR
  EFDKKKLISVETDIVVDHYKEEKFEDRSPAAECLSEKETEELMAWMRNVLGSRVTNVKVT
  LRLDTHPAMVTVLEMGAARHFLRMQQLAKTQEERAQLLQPTLEINPRHALIKKLNQLRAS
  EPGLAQLLVDQIYENAMIAAGLVDDPRAMVGRLNELLVKALERH
• Function: Chaperone that expresses an ATPase activity. Involved in maintaining mitochondrial function and polarization, downstream of PINK1 and mitochondrial complex I. Is a negative regulator of mitochondrial respiration able to modulate the balance between oxidative phosphorylation and aerobic glycolysis. The impact of TRAP1 on mitochondrial respiration is probably mediated by modulation of mitochondrial SRC and inhibition of SDHA.
• Tissue Specificity: Found in skeletal muscle, liver, heart, brain, kidney, pancreas, lung, placenta and bladder. Expression is highly reduced in bladder cancer and renal cell carcinoma specimens compared to healthy tissues, but it is increased in other type of tumors.
• KEGG Pathway:
  Parkinson disease (hsa05012)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
• Reactome Pathway: Respiratory electron transport (R-HSA-611105)

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[1]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[2]
Anaplastic large cell lymphoma	DISP4D1R	Strong	Biomarker	[3]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[4]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[5]
Carcinoma of esophagus	DISS6G4D	Strong	Altered Expression	[6]
Colitis	DISAF7DD	Strong	Biomarker	[7]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[8]
Colorectal neoplasm	DISR1UCN	Strong	Biomarker	[9]
Congenital anomaly of kidney and urinary tract	DIS84IVH	Strong	Genetic Variation	[10]
Crohn disease	DIS2C5Q8	Strong	Biomarker	[7]
Esophageal cancer	DISGB2VN	Strong	Altered Expression	[6]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[6]
Gastric cancer	DISXGOUK	Strong	Biomarker	[11]
Gastric neoplasm	DISOKN4Y	Strong	Biomarker	[11]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[2]
Glioma	DIS5RPEH	Strong	Biomarker	[2]
Hereditary diffuse gastric adenocarcinoma	DISUIBYS	Strong	Biomarker	[11]
Late-onset Parkinson disease	DIS9IOUI	Strong	Genetic Variation	[12]
Lung cancer	DISCM4YA	Strong	Biomarker	[13]
Lung carcinoma	DISTR26C	Strong	Biomarker	[13]
Malignant glioma	DISFXKOV	Strong	Altered Expression	[14]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[15]
Metastatic prostate carcinoma	DISVBEZ9	Strong	Biomarker	[14]
Neoplasm of esophagus	DISOLKAQ	Strong	Altered Expression	[6]
Nephropathy	DISXWP4P	Strong	Biomarker	[16]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[17]
Paraganglioma	DIS2XXH5	Strong	Biomarker	[18]
Parkinson disease	DISQVHKL	Strong	Genetic Variation	[12]
Renal fibrosis	DISMHI3I	Strong	Biomarker	[19]
Systemic lupus erythematosus	DISI1SZ7	Strong	Genetic Variation	[20]
Thyroid gland carcinoma	DISMNGZ0	Strong	Biomarker	[21]
VACTERL/vater association	DISJNE30	Strong	Biomarker	[22]
Carcinoma	DISH9F1N	moderate	Altered Expression	[9]
Colon cancer	DISVC52G	moderate	Altered Expression	[9]
Kidney cancer	DISBIPKM	moderate	Altered Expression	[23]
Lupus nephritis	DISCVGPZ	moderate	Biomarker	[24]
Nephritis	DISQZQ70	moderate	Altered Expression	[24]
Prostate cancer	DISF190Y	moderate	Biomarker	[25]
Prostate carcinoma	DISMJPLE	moderate	Biomarker	[25]
Breast cancer	DIS7DPX1	Limited	Biomarker	[4]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Limited	Altered Expression	[26]
Hepatitis B virus infection	DISLQ2XY	Limited	Altered Expression	[26]
Liver cancer	DISDE4BI	Limited	Altered Expression	[26]
Neuroblastoma	DISVZBI4	Limited	Altered Expression	[27]
Osteoarthritis	DIS05URM	Limited	Biomarker	[28]

3 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 Heat shock protein 75 kDa, mitochondrial (TRAP1).	[29]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Heat shock protein 75 kDa, mitochondrial (TRAP1).	[44]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Heat shock protein 75 kDa, mitochondrial (TRAP1).	[48]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Heat shock protein 75 kDa, mitochondrial (TRAP1).	[30]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Heat shock protein 75 kDa, mitochondrial (TRAP1).	[31]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Heat shock protein 75 kDa, mitochondrial (TRAP1).	[32]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Heat shock protein 75 kDa, mitochondrial (TRAP1).	[33]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Heat shock protein 75 kDa, mitochondrial (TRAP1).	[34]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Heat shock protein 75 kDa, mitochondrial (TRAP1).	[35]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Heat shock protein 75 kDa, mitochondrial (TRAP1).	[36]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Heat shock protein 75 kDa, mitochondrial (TRAP1).	[37]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Heat shock protein 75 kDa, mitochondrial (TRAP1).	[38]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Heat shock protein 75 kDa, mitochondrial (TRAP1).	[39]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Heat shock protein 75 kDa, mitochondrial (TRAP1).	[40]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Heat shock protein 75 kDa, mitochondrial (TRAP1).	[41]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Heat shock protein 75 kDa, mitochondrial (TRAP1).	[42]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil affects the expression of Heat shock protein 75 kDa, mitochondrial (TRAP1).	[43]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Heat shock protein 75 kDa, mitochondrial (TRAP1).	[45]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Heat shock protein 75 kDa, mitochondrial (TRAP1).	[46]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Heat shock protein 75 kDa, mitochondrial (TRAP1).	[47]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Heat shock protein 75 kDa, mitochondrial (TRAP1).	[49]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Heat shock protein 75 kDa, mitochondrial (TRAP1).	[50]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Heat shock protein 75 kDa, mitochondrial (TRAP1).	[51]
	DM9CEI5		decreases the expression of Heat shock protein 75 kDa, mitochondrial (TRAP1).	[52]
SNX-2112	DMB5A80	Investigative	SNX-2112 decreases the expression of Heat shock protein 75 kDa, mitochondrial (TRAP1).	[53]

References

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