Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQESJV4)

• DOT Name: Neurofilament light polypeptide (NEFL)
• Synonyms: NF-L; 68 kDa neurofilament protein; Neurofilament triplet L protein
• Gene Name: NEFL
• Related Disease:
  Astrocytoma
  Charcot marie tooth disease
  Charcot-Marie-Tooth disease type 2
  Glioma
  Neoplasm
  Neuroblastoma
  Adult glioblastoma
  Advanced cancer
  Behavioral variant of frontotemporal dementia
  Bipolar disorder
  Breast cancer
  Breast carcinoma
  Cardiac arrest
  Charcot-Marie-Tooth disease type 1F
  Congenital hypothyroidism
  Corpus callosum, agenesis of
  Delirium
  Encephalitis
  Frontotemporal dementia
  Hereditary motor and sensory neuropathy
  Huntington disease
  Hypothyroidism
  Major depressive disorder
  Mental disorder
  Motor neurone disease
  Parkinson disease
  Peripheral neuropathy
  Primary progressive aphasia
  Prion disease
  Progressive supranuclear palsy
  Relapsing-remitting multiple sclerosis
  Sciatic neuropathy
  Spinal muscular atrophy
  Stroke
  Subarachnoid hemorrhage
  Type-1/2 diabetes
  Amyloidosis
  Nemaline myopathy
  Charcot-Marie-Tooth disease type 2B5
  Charcot-Marie-Tooth disease type 2E
  Charcot-Marie-Tooth disease type 3
  Familial Alzheimer disease
  Glioblastoma multiforme
  Lewy body dementia
  Pick disease
• UniProt ID: NFL_HUMAN
• Pfam ID: PF00038 ; PF04732
• Sequence:
  MSSFSYEPYYSTSYKRRYVETPRVHISSVRSGYSTARSAYSSYSAPVSSSLSVRRSYSSS
  SGSLMPSLENLDLSQVAAISNDLKSIRTQEKAQLQDLNDRFASFIERVHELEQQNKVLEA
  ELLVLRQKHSEPSRFRALYEQEIRDLRLAAEDATNEKQALQGEREGLEETLRNLQARYEE
  EVLSREDAEGRLMEARKGADEAALARAELEKRIDSLMDEISFLKKVHEEEIAELQAQIQY
  AQISVEMDVTKPDLSAALKDIRAQYEKLAAKNMQNAEEWFKSRFTVLTESAAKNTDAVRA
  AKDEVSESRRLLKAKTLEIEACRGMNEALEKQLQELEDKQNADISAMQDTINKLENELRT
  TKSEMARYLKEYQDLLNVKMALDIEIAAYRKLLEGEETRLSFTSVGSITSGYSQSSQVFG
  RSAYGGLQTSSYLMSTRSFPSYYTSHVQEEQIEVEETIEAAKAEEAKDEPPSEGEAEEEE
  KDKEEAEEEEAAEEEEAAKEESEEAKEEEEGGEGEEGEETKEAEEEEKKVEGAGEEQAAK
  KKD
• Function: Neurofilaments usually contain three intermediate filament proteins: NEFL, NEFM, and NEFH which are involved in the maintenance of neuronal caliber. May additionally cooperate with the neuronal intermediate filament proteins PRPH and INA to form neuronal filamentous networks.
• KEGG Pathway:
  Amyotrophic lateral sclerosis (hsa05014)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
• Reactome Pathway:
  Ras activation upon Ca2+ influx through NMDA receptor (R-HSA-442982)
  RAF/MAP kinase cascade (R-HSA-5673001)
  Assembly and cell surface presentation of NMDA receptors (R-HSA-9609736)
  Negative regulation of NMDA receptor-mediated neuronal transmission (R-HSA-9617324)
  Long-term potentiation (R-HSA-9620244)
  Unblocking of NMDA receptors, glutamate binding and activation (R-HSA-438066)

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Astrocytoma	DISL3V18	Definitive	Altered Expression	[1]
Charcot marie tooth disease	DIS3BT2L	Definitive	Autosomal dominant	[2]
Charcot-Marie-Tooth disease type 2	DISR30O9	Definitive	Autosomal recessive	[2]
Glioma	DIS5RPEH	Definitive	Biomarker	[1]
Neoplasm	DISZKGEW	Definitive	Biomarker	[3]
Neuroblastoma	DISVZBI4	Definitive	Altered Expression	[4]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[5]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[6]
Behavioral variant of frontotemporal dementia	DISQHX2V	Strong	Biomarker	[7]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[8]
Breast cancer	DIS7DPX1	Strong	Biomarker	[6]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[6]
Cardiac arrest	DIS9DIA4	Strong	Altered Expression	[9]
Charcot-Marie-Tooth disease type 1F	DISB51V1	Strong	Autosomal recessive	[10]
Congenital hypothyroidism	DISL5XVU	Strong	Biomarker	[11]
Corpus callosum, agenesis of	DISO9P40	Strong	Biomarker	[12]
Delirium	DIS2OKP1	Strong	Biomarker	[13]
Encephalitis	DISLD1RL	Strong	Altered Expression	[14]
Frontotemporal dementia	DISKYHXL	Strong	Biomarker	[15]
Hereditary motor and sensory neuropathy	DISR0X2K	Strong	Biomarker	[16]
Huntington disease	DISQPLA4	Strong	Biomarker	[17]
Hypothyroidism	DISR0H6D	Strong	Therapeutic	[18]
Major depressive disorder	DIS4CL3X	Strong	Altered Expression	[19]
Mental disorder	DIS3J5R8	Strong	Biomarker	[20]
Motor neurone disease	DISUHWUI	Strong	Biomarker	[21]
Parkinson disease	DISQVHKL	Strong	Biomarker	[22]
Peripheral neuropathy	DIS7KN5G	Strong	Biomarker	[12]
Primary progressive aphasia	DISLRYFE	Strong	Biomarker	[23]
Prion disease	DISOUMB0	Strong	Biomarker	[24]
Progressive supranuclear palsy	DISO5KRQ	Strong	Biomarker	[25]
Relapsing-remitting multiple sclerosis	DISSXFCF	Strong	Biomarker	[26]
Sciatic neuropathy	DISMGDKX	Strong	Biomarker	[27]
Spinal muscular atrophy	DISTLKOB	Strong	Biomarker	[28]
Stroke	DISX6UHX	Strong	Biomarker	[29]
Subarachnoid hemorrhage	DISI7I8Y	Strong	Biomarker	[30]
Type-1/2 diabetes	DISIUHAP	Strong	Altered Expression	[31]
Amyloidosis	DISHTAI2	moderate	Biomarker	[32]
Nemaline myopathy	DIS5IYLY	moderate	Biomarker	[33]
Charcot-Marie-Tooth disease type 2B5	DISXLR5C	Supportive	Autosomal recessive	[34]
Charcot-Marie-Tooth disease type 2E	DISVZMQ8	Supportive	Autosomal dominant	[35]
Charcot-Marie-Tooth disease type 3	DIS6DQK1	Limited	Biomarker	[16]
Familial Alzheimer disease	DISE75U4	Limited	Biomarker	[36]
Glioblastoma multiforme	DISK8246	Limited	Biomarker	[5]
Lewy body dementia	DISAE66J	Limited	Genetic Variation	[37]
Pick disease	DISP6X50	Limited	Biomarker	[15]

28 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 Neurofilament light polypeptide (NEFL).	[38]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Neurofilament light polypeptide (NEFL).	[39]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Neurofilament light polypeptide (NEFL).	[40]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Neurofilament light polypeptide (NEFL).	[41]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Neurofilament light polypeptide (NEFL).	[42]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Neurofilament light polypeptide (NEFL).	[43]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Neurofilament light polypeptide (NEFL).	[44]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Neurofilament light polypeptide (NEFL).	[45]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Neurofilament light polypeptide (NEFL).	[46]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Neurofilament light polypeptide (NEFL).	[47]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Neurofilament light polypeptide (NEFL).	[48]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Neurofilament light polypeptide (NEFL).	[46]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Neurofilament light polypeptide (NEFL).	[49]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Neurofilament light polypeptide (NEFL).	[39]
Amphotericin B	DMTAJQE	Approved	Amphotericin B decreases the expression of Neurofilament light polypeptide (NEFL).	[50]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of Neurofilament light polypeptide (NEFL).	[51]
Cocaine	DMSOX7I	Approved	Cocaine decreases the expression of Neurofilament light polypeptide (NEFL).	[52]
Alitretinoin	DMME8LH	Approved	Alitretinoin decreases the expression of Neurofilament light polypeptide (NEFL).	[39]
Acocantherin	DM7JT24	Approved	Acocantherin decreases the expression of Neurofilament light polypeptide (NEFL).	[53]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Neurofilament light polypeptide (NEFL).	[46]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol decreases the expression of Neurofilament light polypeptide (NEFL).	[54]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Neurofilament light polypeptide (NEFL).	[46]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Neurofilament light polypeptide (NEFL).	[56]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Neurofilament light polypeptide (NEFL).	[57]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Neurofilament light polypeptide (NEFL).	[58]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Neurofilament light polypeptide (NEFL).	[59]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Neurofilament light polypeptide (NEFL).	[60]
all-trans-4-oxo-retinoic acid	DMM2R1N	Investigative	all-trans-4-oxo-retinoic acid decreases the expression of Neurofilament light polypeptide (NEFL).	[39]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Neurofilament light polypeptide (NEFL).	[55]

References

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