Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTH9BY8Y)

• DOT Name: Sialidase-1 (NEU1)
• Synonyms: EC 3.2.1.18; Acetylneuraminyl hydrolase; G9 sialidase; Lysosomal sialidase; N-acetyl-alpha-neuraminidase 1
• Gene Name: NEU1
• Related Disease:
  Hyperglycemia
  Sialidosis
  Sialidosis type 2
  Action myoclonus-renal failure syndrome
  Adenocarcinoma
  Adult glioblastoma
  Alzheimer disease
  Arteriosclerosis
  Atherosclerosis
  Bladder transitional cell carcinoma
  Bone osteosarcoma
  Clear cell renal carcinoma
  Dentatorubral-pallidoluysian atrophy
  Ductal breast carcinoma in situ
  Galactosialidosis
  GM1 gangliosidosis
  Hepatocellular carcinoma
  Hydrops fetalis
  Intellectual disability
  Lung cancer
  Lung carcinoma
  Metastatic malignant neoplasm
  Mucolipidosis
  Non-small-cell lung cancer
  Osteosarcoma
  Progressive myoclonus epilepsy
  Renal cell carcinoma
  Rheumatoid arthritis
  Serous cystadenocarcinoma
  Stomach cancer
  Systemic lupus erythematosus
  Uterine serous carcinoma
  Vitiligo
  Colorectal carcinoma
  Lysosomal storage disease
  Melanoma
  Congenital sialidosis type 2
  Juvenile sialidosis type 2
  Sialidosis type 1
  Autoimmune disease
  Breast neoplasm
  Carcinoma
  Endometrial cancer
  Endometrial carcinoma
  Gastric cancer
  Glioblastoma multiforme
  Non-immune hydrops fetalis
  Prostate cancer
  Prostate carcinoma
  Schizophrenia
• UniProt ID: NEUR1_HUMAN
• EC Number: 3.2.1.18
• Pfam ID: PF13088
• Sequence:
  MTGERPSTALPDRRWGPRILGFWGGCRVWVFAAIFLLLSLAASWSKAENDFGLVQPLVTM
  EQLLWVSGRQIGSVDTFRIPLITATPRGTLLAFAEARKMSSSDEGAKFIALRRSMDQGST
  WSPTAFIVNDGDVPDGLNLGAVVSDVETGVVFLFYSLCAHKAGCQVASTMLVWSKDDGVS
  WSTPRNLSLDIGTEVFAPGPGSGIQKQREPRKGRLIVCGHGTLERDGVFCLLSDDHGASW
  RYGSGVSGIPYGQPKQENDFNPDECQPYELPDGSVVINARNQNNYHCHCRIVLRSYDACD
  TLRPRDVTFDPELVDPVVAAGAVVTSSGIVFFSNPAHPEFRVNLTLRWSFSNGTSWRKET
  VQLWPGPSGYSSLATLEGSMDGEEQAPQLYVLYEKGRNHYTESISVAKISVYGTL
• Function: Catalyzes the removal of sialic acid (N-acetylneuraminic acid) moieties from glycoproteins and glycolipids. To be active, it is strictly dependent on its presence in the multienzyme complex. Appears to have a preference for alpha 2-3 and alpha 2-6 sialyl linkage.
• Tissue Specificity: Highly expressed in pancreas, followed by skeletal muscle, kidney, placenta, heart, lung and liver. Weakly expressed in brain.
• KEGG Pathway:
  Other glycan degradation (hsa00511)
  Sphingolipid metabolism (hsa00600)
  Metabolic pathways (hsa01100)
  Lysosome (hsa04142)
• Reactome Pathway:
  Defective NEU1 causes sialidosis (R-HSA-4341670)
  Neutrophil degranulation (R-HSA-6798695)
  Glycosphingolipid catabolism (R-HSA-9840310)
  Sialic acid metabolism (R-HSA-4085001)

Molecular Interaction Atlas (MIA) of This DOT

50 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hyperglycemia	DIS0BZB5	Definitive	Biomarker	[1]
Sialidosis	DISF3OAZ	Definitive	Autosomal recessive	[2]
Sialidosis type 2	DIS5ZHNR	Definitive	Autosomal recessive	[3]
Action myoclonus-renal failure syndrome	DISI2BZN	Strong	Biomarker	[4]
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[5]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[6]
Alzheimer disease	DISF8S70	Strong	Biomarker	[7]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[8]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[8]
Bladder transitional cell carcinoma	DISNL46A	Strong	Altered Expression	[9]
Bone osteosarcoma	DIST1004	Strong	Altered Expression	[10]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[11]
Dentatorubral-pallidoluysian atrophy	DISHWE0K	Strong	Biomarker	[4]
Ductal breast carcinoma in situ	DISLCJY7	Strong	Biomarker	[12]
Galactosialidosis	DIS0XSEE	Strong	Biomarker	[13]
GM1 gangliosidosis	DISN3L2M	Strong	Biomarker	[14]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[15]
Hydrops fetalis	DISD9BBF	Strong	Biomarker	[16]
Intellectual disability	DISMBNXP	Strong	Altered Expression	[14]
Lung cancer	DISCM4YA	Strong	Genetic Variation	[17]
Lung carcinoma	DISTR26C	Strong	Biomarker	[18]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[19]
Mucolipidosis	DISOZ8DI	Strong	Genetic Variation	[20]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[18]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[10]
Progressive myoclonus epilepsy	DISAMCNS	Strong	Biomarker	[4]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[11]
Rheumatoid arthritis	DISTSB4J	Strong	Altered Expression	[21]
Serous cystadenocarcinoma	DISVK716	Strong	Altered Expression	[22]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[23]
Systemic lupus erythematosus	DISI1SZ7	Strong	Altered Expression	[24]
Uterine serous carcinoma	DISAW5MD	Strong	Biomarker	[25]
Vitiligo	DISR05SL	Strong	Genetic Variation	[26]
Colorectal carcinoma	DIS5PYL0	moderate	Genetic Variation	[27]
Lysosomal storage disease	DIS6QM6U	moderate	Altered Expression	[28]
Melanoma	DIS1RRCY	moderate	Biomarker	[29]
Congenital sialidosis type 2	DISHZQ6A	Supportive	Autosomal recessive	[30]
Juvenile sialidosis type 2	DISUSV7Y	Supportive	Autosomal recessive	[31]
Sialidosis type 1	DISQGR4F	Supportive	Autosomal recessive	[32]
Autoimmune disease	DISORMTM	Limited	Altered Expression	[28]
Breast neoplasm	DISNGJLM	Limited	Altered Expression	[33]
Carcinoma	DISH9F1N	Limited	Altered Expression	[34]
Endometrial cancer	DISW0LMR	Limited	Biomarker	[35]
Endometrial carcinoma	DISXR5CY	Limited	Biomarker	[35]
Gastric cancer	DISXGOUK	Limited	Altered Expression	[23]
Glioblastoma multiforme	DISK8246	Limited	Altered Expression	[36]
Non-immune hydrops fetalis	DISPUY8C	Limited	Genetic Variation	[37]
Prostate cancer	DISF190Y	Limited	Biomarker	[38]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[38]
Schizophrenia	DISSRV2N	Limited	Genetic Variation	[39]

27 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 Sialidase-1 (NEU1).	[40]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Sialidase-1 (NEU1).	[41]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Sialidase-1 (NEU1).	[42]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Sialidase-1 (NEU1).	[43]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Sialidase-1 (NEU1).	[44]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Sialidase-1 (NEU1).	[45]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Sialidase-1 (NEU1).	[47]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Sialidase-1 (NEU1).	[47]
Gemcitabine	DMSE3I7	Approved	Gemcitabine increases the expression of Sialidase-1 (NEU1).	[48]
Sulindac	DM2QHZU	Approved	Sulindac increases the expression of Sialidase-1 (NEU1).	[49]
Fluoxetine	DM3PD2C	Approved	Fluoxetine increases the expression of Sialidase-1 (NEU1).	[50]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Sialidase-1 (NEU1).	[47]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Sialidase-1 (NEU1).	[51]
MGCD-0103	DM726HX	Phase 2	MGCD-0103 decreases the expression of Sialidase-1 (NEU1).	[47]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Sialidase-1 (NEU1).	[53]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Sialidase-1 (NEU1).	[54]
Tacedinaline	DM1Z74X	Discontinued in Phase 2	Tacedinaline decreases the expression of Sialidase-1 (NEU1).	[47]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Sialidase-1 (NEU1).	[55]
Scriptaid	DM9JZ21	Preclinical	Scriptaid increases the expression of Sialidase-1 (NEU1).	[47]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Sialidase-1 (NEU1).	[56]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Sialidase-1 (NEU1).	[47]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Sialidase-1 (NEU1).	[57]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Sialidase-1 (NEU1).	[58]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal increases the expression of Sialidase-1 (NEU1).	[59]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid increases the expression of Sialidase-1 (NEU1).	[47]
PP-242	DM2348V	Investigative	PP-242 decreases the expression of Sialidase-1 (NEU1).	[60]
Octanedioic acid bis-hydroxyamide	DMJNQ9K	Investigative	Octanedioic acid bis-hydroxyamide increases the expression of Sialidase-1 (NEU1).	[47]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Sialidase-1 (NEU1).	[46]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Sialidase-1 (NEU1).	[52]

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