Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT14KP4B)

• DOT Name: Triosephosphate isomerase (TPI1)
• Synonyms: TIM; EC 5.3.1.1; Methylglyoxal synthase; EC 4.2.3.3; Triose-phosphate isomerase
• Gene Name: TPI1
• Related Disease:
  Adult glioblastoma
  Esophageal squamous cell carcinoma
  Glioblastoma multiforme
  Nervous system disease
  Thyroid gland papillary carcinoma
  Arteriosclerosis
  Asthma
  Atherosclerosis
  Autism spectrum disorder
  Bipolar disorder
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Cardiac failure
  Chagas disease
  Congenital nonspherocytic hemolytic anemia
  Congestive heart failure
  Dementia
  Familial Alzheimer disease
  Glioma
  Inborn error of metabolism
  Intellectual disability
  Lung cancer
  Lung carcinoma
  Metabolic disorder
  Osteoarthritis
  Osteoporosis
  Rheumatoid arthritis
  Schizophrenia
  Squamous cell carcinoma
  Triosephosphate isomerase deficiency
  Tuberculosis
  Autoimmune disease
  Gastric cancer
  Giardiasis
  Ocular hypertension
  Stomach cancer
  Lung adenocarcinoma
  Multiple sclerosis
  Adenocarcinoma
  Alzheimer disease
  Colorectal carcinoma
  Hemolytic anemia
  Melanoma
  Neuroblastoma
  Neuromuscular disease
• UniProt ID: TPIS_HUMAN
• PDB ID: 1HTI; 1KLG; 1KLU; 1WYI; 2IAM; 2IAN; 2JK2; 2VOM; 4BR1; 4E41; 4POC; 4POD; 4UNK; 4UNL; 4ZVJ; 6C2G; 6D43; 6NLH; 6UP1; 6UP5; 6UP8; 6UPF; 7RDE; 7SX1; 7T0Q; 7UXB; 7UXV
• EC Number: 4.2.3.3; 5.3.1.1
• Pfam ID: PF00121
• Sequence:
  MAPSRKFFVGGNWKMNGRKQSLGELIGTLNAAKVPADTEVVCAPPTAYIDFARQKLDPKI
  AVAAQNCYKVTNGAFTGEISPGMIKDCGATWVVLGHSERRHVFGESDELIGQKVAHALAE
  GLGVIACIGEKLDEREAGITEKVVFEQTKVIADNVKDWSKVVLAYEPVWAIGTGKTATPQ
  QAQEVHEKLRGWLKSNVSDAVAQSTRIIYGGSVTGATCKELASQPDVDGFLVGGASLKPE
  FVDIINAKQ
• Function: Triosephosphate isomerase is an extremely efficient metabolic enzyme that catalyzes the interconversion between dihydroxyacetone phosphate (DHAP) and D-glyceraldehyde-3-phosphate (G3P) in glycolysis and gluconeogenesis; It is also responsible for the non-negligible production of methylglyoxal a reactive cytotoxic side-product that modifies and can alter proteins, DNA and lipids.
• KEGG Pathway:
  Glycolysis / Gluconeogenesis (hsa00010)
  Fructose and mannose metabolism (hsa00051)
  Inositol phosphate metabolism (hsa00562)
  Metabolic pathways (hsa01100)
  Carbon metabolism (hsa01200)
  Biosynthesis of amino acids (hsa01230)
• Reactome Pathway:
  Gluconeogenesis (R-HSA-70263)
  Glycolysis (R-HSA-70171)
• BioCyc Pathway: MetaCyc:HS03441-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	Definitive	Biomarker	[1]
Esophageal squamous cell carcinoma	DIS5N2GV	Definitive	Biomarker	[2]
Glioblastoma multiforme	DISK8246	Definitive	Biomarker	[1]
Nervous system disease	DISJ7GGT	Definitive	Biomarker	[3]
Thyroid gland papillary carcinoma	DIS48YMM	Definitive	Biomarker	[4]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[5]
Asthma	DISW9QNS	Strong	Genetic Variation	[6]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[5]
Autism spectrum disorder	DISXK8NV	Strong	Genetic Variation	[7]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[8]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[9]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[9]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[10]
Cardiac failure	DISDC067	Strong	Biomarker	[11]
Chagas disease	DIS8KNVF	Strong	Biomarker	[12]
Congenital nonspherocytic hemolytic anemia	DISEJNS0	Strong	Biomarker	[13]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[11]
Dementia	DISXL1WY	Strong	Biomarker	[14]
Familial Alzheimer disease	DISE75U4	Strong	Biomarker	[15]
Glioma	DIS5RPEH	Strong	Biomarker	[16]
Inborn error of metabolism	DISO5FAY	Strong	Biomarker	[13]
Intellectual disability	DISMBNXP	Strong	Biomarker	[17]
Lung cancer	DISCM4YA	Strong	Biomarker	[18]
Lung carcinoma	DISTR26C	Strong	Biomarker	[18]
Metabolic disorder	DIS71G5H	Strong	Biomarker	[19]
Osteoarthritis	DIS05URM	Strong	Biomarker	[20]
Osteoporosis	DISF2JE0	Strong	Biomarker	[21]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[22]
Schizophrenia	DISSRV2N	Strong	Biomarker	[23]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[24]
Triosephosphate isomerase deficiency	DIS5QTVL	Strong	Autosomal recessive	[25]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[26]
Autoimmune disease	DISORMTM	moderate	Genetic Variation	[27]
Gastric cancer	DISXGOUK	moderate	Altered Expression	[28]
Giardiasis	DISWUNWK	moderate	Genetic Variation	[29]
Ocular hypertension	DISC2BT9	moderate	Biomarker	[30]
Stomach cancer	DISKIJSX	moderate	Altered Expression	[28]
Lung adenocarcinoma	DISD51WR	Disputed	Biomarker	[31]
Multiple sclerosis	DISB2WZI	Disputed	Biomarker	[32]
Adenocarcinoma	DIS3IHTY	Limited	Biomarker	[33]
Alzheimer disease	DISF8S70	Limited	Biomarker	[34]
Colorectal carcinoma	DIS5PYL0	Limited	Genetic Variation	[35]
Hemolytic anemia	DIS803XQ	Limited	Genetic Variation	[17]
Melanoma	DIS1RRCY	Limited	Biomarker	[36]
Neuroblastoma	DISVZBI4	Limited	Genetic Variation	[37]
Neuromuscular disease	DISQTIJZ	Limited	Biomarker	[13]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Zalcitabine	DMH7MUV	Approved	Triosephosphate isomerase (TPI1) increases the Cardiotoxicity ADR of Zalcitabine.	[70]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Triosephosphate isomerase (TPI1).	[38]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Triosephosphate isomerase (TPI1).	[39]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Triosephosphate isomerase (TPI1).	[40]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Triosephosphate isomerase (TPI1).	[41]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Triosephosphate isomerase (TPI1).	[42]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Triosephosphate isomerase (TPI1).	[43]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Triosephosphate isomerase (TPI1).	[44]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Triosephosphate isomerase (TPI1).	[45]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Triosephosphate isomerase (TPI1).	[46]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Triosephosphate isomerase (TPI1).	[47]
Selenium	DM25CGV	Approved	Selenium increases the expression of Triosephosphate isomerase (TPI1).	[48]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Triosephosphate isomerase (TPI1).	[49]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Triosephosphate isomerase (TPI1).	[50]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Triosephosphate isomerase (TPI1).	[51]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of Triosephosphate isomerase (TPI1).	[52]
Menthol	DMG2KW7	Approved	Menthol increases the expression of Triosephosphate isomerase (TPI1).	[54]
Capsaicin	DMGMF6V	Approved	Capsaicin increases the expression of Triosephosphate isomerase (TPI1).	[55]
Ibuprofen	DM8VCBE	Approved	Ibuprofen increases the expression of Triosephosphate isomerase (TPI1).	[56]
Acocantherin	DM7JT24	Approved	Acocantherin affects the expression of Triosephosphate isomerase (TPI1).	[57]
Etretinate	DM2CZFA	Approved	Etretinate decreases the expression of Triosephosphate isomerase (TPI1).	[59]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Triosephosphate isomerase (TPI1).	[60]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Triosephosphate isomerase (TPI1).	[48]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Triosephosphate isomerase (TPI1).	[63]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Triosephosphate isomerase (TPI1).	[64]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Triosephosphate isomerase (TPI1).	[65]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Triosephosphate isomerase (TPI1).	[66]
CH-223191	DMMJZYC	Investigative	CH-223191 increases the expression of Triosephosphate isomerase (TPI1).	[68]
PP-242	DM2348V	Investigative	PP-242 decreases the expression of Triosephosphate isomerase (TPI1).	[69]
Alpha-naphthoflavone	DMELOIQ	Investigative	Alpha-naphthoflavone increases the expression of Triosephosphate isomerase (TPI1).	[68]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	Etoposide increases the phosphorylation of Triosephosphate isomerase (TPI1).	[53]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Triosephosphate isomerase (TPI1).	[61]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Triosephosphate isomerase (TPI1).	[62]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Dihydroartemisinin	DMBXVMZ	Approved	Dihydroartemisinin affects the binding of Triosephosphate isomerase (TPI1).	[58]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal affects the binding of Triosephosphate isomerase (TPI1).	[15]

References

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