Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT49ONSE)

• DOT Name: Inositol-3-phosphate synthase 1 (ISYNA1)
• Synonyms: IPS 1; EC 5.5.1.4; Myo-inositol 1-phosphate synthase; MI-1-P synthase; MIP synthase; hIPS; Myo-inositol 1-phosphate synthase A1; hINO1
• Gene Name: ISYNA1
• Related Disease:
  Melanoma
  Myocardial infarction
  Asthma
  Breast neoplasm
  Bronchiolitis
  Cardiac failure
  Colorectal carcinoma
  Congestive heart failure
  Coronary atherosclerosis
  Coronary heart disease
  Gastric cancer
  Glioma
  Head-neck squamous cell carcinoma
  Hepatocellular carcinoma
  High blood pressure
  Hypertension, pregnancy-induced
  Inflammatory bowel disease
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Malaria
  Osteoarthritis
  Parkinson disease
  Polycystic ovarian syndrome
  Prostate cancer
  Prostate carcinoma
  Psoriasis
  Respiratory syncytial virus infection
  Stomach cancer
  Type-1/2 diabetes
  Vascular disease
  Cystic fibrosis
  Triple negative breast cancer
  Type-1 diabetes
  Adenocarcinoma
  Bladder cancer
  Breast cancer
  Breast carcinoma
  Coeliac disease
  Colon cancer
  Colon carcinoma
  Mental disorder
  Rheumatoid arthritis
  Urinary bladder cancer
  Urinary bladder neoplasm
• UniProt ID: INO1_HUMAN
• EC Number: 5.5.1.4
• Pfam ID: PF01658 ; PF07994
• Sequence:
  MEAAAQFFVESPDVVYGPEAIEAQYEYRTTRVSREGGVLKVHPTSTRFTFRTARQVPRLG
  VMLVGWGGNNGSTLTAAVLANRLRLSWPTRSGRKEANYYGSLTQAGTVSLGLDAEGQEVF
  VPFSAVLPMVAPNDLVFDGWDISSLNLAEAMRRAKVLDWGLQEQLWPHMEALRPRPSVYI
  PEFIAANQSARADNLIPGSRAQQLEQIRRDIRDFRSSAGLDKVIVLWTANTERFCEVIPG
  LNDTAENLLRTIELGLEVSPSTLFAVASILEGCAFLNGSPQNTLVPGALELAWQHRVFVG
  GDDFKSGQTKVKSVLVDFLIGSGLKTMSIVSYNHLGNNDGENLSAPLQFRSKEVSKSNVV
  DDMVQSNPVLYTPGEEPDHCVVIKYVPYVGDSKRALDEYTSELMLGGTNTLVLHNTCEDS
  LLAAPIMLDLALLTELCQRVSFCTDMDPEPQTFHPVLSLLSFLFKAPLVPPGSPVVNALF
  RQRSCIENILRACVGLPPQNHMLLEHKMERPGPSLKRVGPVAATYPMLNKKGPVPAATNG
  CTGDANGHLQEEPPMPTT
• Function: Key enzyme in myo-inositol biosynthesis pathway that catalyzes the conversion of glucose 6-phosphate to 1-myo-inositol 1-phosphate in a NAD-dependent manner. Rate-limiting enzyme in the synthesis of all inositol-containing compounds.
• Tissue Specificity: Highly expressed in testis, ovary, heart, placenta and pancreas. Weakly expressed in blood leukocyte, thymus, skeletal muscle and colon.
• KEGG Pathway:
  Inositol phosphate metabolism (hsa00562)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Synthesis of IP2, IP, and Ins in the cytosol (R-HSA-1855183)

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Melanoma	DIS1RRCY	Definitive	Altered Expression	[1]
Myocardial infarction	DIS655KI	Definitive	Altered Expression	[2]
Asthma	DISW9QNS	Strong	Altered Expression	[3]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[4]
Bronchiolitis	DISEE9BG	Strong	Biomarker	[5]
Cardiac failure	DISDC067	Strong	Altered Expression	[6]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[7]
Congestive heart failure	DIS32MEA	Strong	Altered Expression	[6]
Coronary atherosclerosis	DISKNDYU	Strong	Biomarker	[8]
Coronary heart disease	DIS5OIP1	Strong	Biomarker	[9]
Gastric cancer	DISXGOUK	Strong	Genetic Variation	[10]
Glioma	DIS5RPEH	Strong	Biomarker	[11]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Altered Expression	[12]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[13]
High blood pressure	DISY2OHH	Strong	Genetic Variation	[14]
Hypertension, pregnancy-induced	DISHNU25	Strong	Altered Expression	[15]
Inflammatory bowel disease	DISGN23E	Strong	Altered Expression	[16]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[17]
Lung cancer	DISCM4YA	Strong	Biomarker	[17]
Lung carcinoma	DISTR26C	Strong	Biomarker	[17]
Malaria	DISQ9Y50	Strong	Genetic Variation	[18]
Osteoarthritis	DIS05URM	Strong	Altered Expression	[19]
Parkinson disease	DISQVHKL	Strong	Altered Expression	[20]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Biomarker	[21]
Prostate cancer	DISF190Y	Strong	Biomarker	[22]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[22]
Psoriasis	DIS59VMN	Strong	Genetic Variation	[23]
Respiratory syncytial virus infection	DIS7FWHY	Strong	Altered Expression	[24]
Stomach cancer	DISKIJSX	Strong	Genetic Variation	[10]
Type-1/2 diabetes	DISIUHAP	Strong	Altered Expression	[25]
Vascular disease	DISVS67S	Strong	Biomarker	[26]
Cystic fibrosis	DIS2OK1Q	moderate	Altered Expression	[27]
Triple negative breast cancer	DISAMG6N	moderate	Biomarker	[28]
Type-1 diabetes	DIS7HLUB	Disputed	Altered Expression	[25]
Adenocarcinoma	DIS3IHTY	Limited	Altered Expression	[29]
Bladder cancer	DISUHNM0	Limited	Altered Expression	[30]
Breast cancer	DIS7DPX1	Limited	Altered Expression	[31]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[31]
Coeliac disease	DISIY60C	Limited	Altered Expression	[32]
Colon cancer	DISVC52G	Limited	Altered Expression	[33]
Colon carcinoma	DISJYKUO	Limited	Altered Expression	[33]
Mental disorder	DIS3J5R8	Limited	Biomarker	[34]
Rheumatoid arthritis	DISTSB4J	Limited	Genetic Variation	[35]
Urinary bladder cancer	DISDV4T7	Limited	Altered Expression	[30]
Urinary bladder neoplasm	DIS7HACE	Limited	Altered Expression	[30]

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 Inositol-3-phosphate synthase 1 (ISYNA1).	[36]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Inositol-3-phosphate synthase 1 (ISYNA1).	[49]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Inositol-3-phosphate synthase 1 (ISYNA1).	[51]

19 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 Inositol-3-phosphate synthase 1 (ISYNA1).	[37]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Inositol-3-phosphate synthase 1 (ISYNA1).	[38]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Inositol-3-phosphate synthase 1 (ISYNA1).	[39]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Inositol-3-phosphate synthase 1 (ISYNA1).	[40]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Inositol-3-phosphate synthase 1 (ISYNA1).	[41]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Inositol-3-phosphate synthase 1 (ISYNA1).	[42]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Inositol-3-phosphate synthase 1 (ISYNA1).	[43]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Inositol-3-phosphate synthase 1 (ISYNA1).	[44]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Inositol-3-phosphate synthase 1 (ISYNA1).	[37]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Inositol-3-phosphate synthase 1 (ISYNA1).	[45]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Inositol-3-phosphate synthase 1 (ISYNA1).	[42]
Selenium	DM25CGV	Approved	Selenium increases the expression of Inositol-3-phosphate synthase 1 (ISYNA1).	[46]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Inositol-3-phosphate synthase 1 (ISYNA1).	[47]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Inositol-3-phosphate synthase 1 (ISYNA1).	[48]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Inositol-3-phosphate synthase 1 (ISYNA1).	[46]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Inositol-3-phosphate synthase 1 (ISYNA1).	[50]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Inositol-3-phosphate synthase 1 (ISYNA1).	[52]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Inositol-3-phosphate synthase 1 (ISYNA1).	[53]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Inositol-3-phosphate synthase 1 (ISYNA1).	[54]

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