Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQH9HM3)

• DOT Name: Nuclear factor interleukin-3-regulated protein (NFIL3)
• Synonyms: E4 promoter-binding protein 4; Interleukin-3 promoter transcriptional activator; Interleukin-3-binding protein 1; Transcriptional activator NF-IL3A
• Gene Name: NFIL3
• Related Disease:
  Colitis
  Crohn disease
  Advanced cancer
  Arthritis
  Autoimmune disease
  Bone disease
  Cardiac failure
  Congestive heart failure
  Glioma
  Hereditary sensory and autonomic neuropathy type 1
  High blood pressure
  Inflammatory bowel disease
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Neoplasm
  Ovarian neoplasm
  Promyelocytic leukaemia
  Sleep-wake disorder
  Systemic lupus erythematosus
  Choriocarcinoma
  Colorectal carcinoma
  Acute lymphocytic leukaemia
  Amyotrophic lateral sclerosis
  Asthma
  Breast cancer
  Breast carcinoma
  Hyperglycemia
  Lymphoid leukemia
  Rheumatoid arthritis
  Thyroid cancer
  Thyroid gland carcinoma
  Thyroid tumor
  Type-1/2 diabetes
• UniProt ID: NFIL3_HUMAN
• Pfam ID: PF07716 ; PF06529
• Sequence:
  MQLRKMQTVKKEQASLDASSNVDKMMVLNSALTEVSEDSTTGEELLLSEGSVGKNKSSAC
  RRKREFIPDEKKDAMYWEKRRKNNEAAKRSREKRRLNDLVLENKLIALGEENATLKAELL
  SLKLKFGLISSTAYAQEIQKLSNSTAVYFQDYQTSKSNVSSFVDEHEPSMVSSSCISVIK
  HSPQSSLSDVSEVSSVEHTQESSVQGSCRSPENKFQIIKQEPMELESYTREPRDDRGSYT
  ASIYQNYMGNSFSGYSHSPPLLQVNRSSSNSPRTSETDDGVVGKSSDGEDEQQVPKGPIH
  SPVELKHVHATVVKVPEVNSSALPHKLRIKAKAMQIKVEAFDNEFEATQKLSSPIDMTSK
  RHFELEKHSAPSMVHSSLTPFSVQVTNIQDWSLKSEHWHQKELSGKTQNSFKTGVVEMKD
  SGYKVSDPENLYLKQGIANLSAEVVSLKRLIATQPISASDSG
• Function: Acts as a transcriptional regulator that recognizes and binds to the sequence 5'-[GA]TTA[CT]GTAA[CT]-3', a sequence present in many cellular and viral promoters. Represses transcription from promoters with activating transcription factor (ATF) sites. Represses promoter activity in osteoblasts. Represses transcriptional activity of PER1. Represses transcriptional activity of PER2 via the B-site on the promoter. Activates transcription from the interleukin-3 promoter in T-cells. Competes for the same consensus-binding site with PAR DNA-binding factors (DBP, HLF and TEF). Component of the circadian clock that acts as a negative regulator for the circadian expression of PER2 oscillation in the cell-autonomous core clock. Protects pro-B cells from programmed cell death. Represses the transcription of CYP2A5. Positively regulates the expression and activity of CES2 by antagonizing the repressive action of NR1D1 on CES2. Required for the development of natural killer cell precursors.
• Tissue Specificity: Expressed in bladder stomach, thyroid, spinal cord, lymph node, trachea, adrenal gland, bone marrow and muscle.
• KEGG Pathway: Circadian rhythm (hsa04710)
• Reactome Pathway: Circadian Clock (R-HSA-400253)

Molecular Interaction Atlas (MIA) of This DOT

34 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colitis	DISAF7DD	Definitive	Biomarker	[1]
Crohn disease	DIS2C5Q8	Definitive	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Arthritis	DIST1YEL	Strong	Genetic Variation	[3]
Autoimmune disease	DISORMTM	Strong	Biomarker	[4]
Bone disease	DISE1F82	Strong	Altered Expression	[5]
Cardiac failure	DISDC067	Strong	Biomarker	[6]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[6]
Glioma	DIS5RPEH	Strong	Biomarker	[7]
Hereditary sensory and autonomic neuropathy type 1	DISLSPO4	Strong	Genetic Variation	[8]
High blood pressure	DISY2OHH	Strong	Biomarker	[9]
Inflammatory bowel disease	DISGN23E	Strong	Altered Expression	[1]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[10]
Lung cancer	DISCM4YA	Strong	Biomarker	[10]
Lung carcinoma	DISTR26C	Strong	Biomarker	[10]
Neoplasm	DISZKGEW	Strong	Altered Expression	[10]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[11]
Promyelocytic leukaemia	DISYGG13	Strong	Biomarker	[12]
Sleep-wake disorder	DISOBM0Q	Strong	Biomarker	[13]
Systemic lupus erythematosus	DISI1SZ7	Strong	Altered Expression	[4]
Choriocarcinoma	DISDBVNL	moderate	Biomarker	[14]
Colorectal carcinoma	DIS5PYL0	moderate	Biomarker	[15]
Acute lymphocytic leukaemia	DISPX75S	Limited	Altered Expression	[16]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Altered Expression	[17]
Asthma	DISW9QNS	Limited	Biomarker	[18]
Breast cancer	DIS7DPX1	Limited	Altered Expression	[19]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[19]
Hyperglycemia	DIS0BZB5	Limited	Altered Expression	[20]
Lymphoid leukemia	DIS65TYQ	Limited	Altered Expression	[16]
Rheumatoid arthritis	DISTSB4J	Limited	Biomarker	[21]
Thyroid cancer	DIS3VLDH	Limited	Biomarker	[2]
Thyroid gland carcinoma	DISMNGZ0	Limited	Biomarker	[2]
Thyroid tumor	DISLVKMD	Limited	Biomarker	[2]
Type-1/2 diabetes	DISIUHAP	Limited	Altered Expression	[22]

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 Nuclear factor interleukin-3-regulated protein (NFIL3).	[23]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Nuclear factor interleukin-3-regulated protein (NFIL3).	[24]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Nuclear factor interleukin-3-regulated protein (NFIL3).	[25]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Nuclear factor interleukin-3-regulated protein (NFIL3).	[26]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Nuclear factor interleukin-3-regulated protein (NFIL3).	[27]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate affects the expression of Nuclear factor interleukin-3-regulated protein (NFIL3).	[28]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Nuclear factor interleukin-3-regulated protein (NFIL3).	[29]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Nuclear factor interleukin-3-regulated protein (NFIL3).	[30]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Nuclear factor interleukin-3-regulated protein (NFIL3).	[32]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Nuclear factor interleukin-3-regulated protein (NFIL3).	[33]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Nuclear factor interleukin-3-regulated protein (NFIL3).	[34]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Nuclear factor interleukin-3-regulated protein (NFIL3).	[35]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Nuclear factor interleukin-3-regulated protein (NFIL3).	[36]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Nuclear factor interleukin-3-regulated protein (NFIL3).	[37]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Nuclear factor interleukin-3-regulated protein (NFIL3).	[38]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Nuclear factor interleukin-3-regulated protein (NFIL3).	[39]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Nuclear factor interleukin-3-regulated protein (NFIL3).	[40]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Nuclear factor interleukin-3-regulated protein (NFIL3).	[41]
Sulindac	DM2QHZU	Approved	Sulindac increases the expression of Nuclear factor interleukin-3-regulated protein (NFIL3).	[42]
Diphenylpyraline	DMW4X37	Approved	Diphenylpyraline decreases the expression of Nuclear factor interleukin-3-regulated protein (NFIL3).	[43]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Nuclear factor interleukin-3-regulated protein (NFIL3).	[45]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Nuclear factor interleukin-3-regulated protein (NFIL3).	[47]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Nuclear factor interleukin-3-regulated protein (NFIL3).	[48]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Nuclear factor interleukin-3-regulated protein (NFIL3).	[49]
Milchsaure	DM462BT	Investigative	Milchsaure affects the expression of Nuclear factor interleukin-3-regulated protein (NFIL3).	[50]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Nuclear factor interleukin-3-regulated protein (NFIL3).	[51]
geraniol	DMS3CBD	Investigative	geraniol increases the expression of Nuclear factor interleukin-3-regulated protein (NFIL3).	[53]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID increases the expression of Nuclear factor interleukin-3-regulated protein (NFIL3).	[54]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Nuclear factor interleukin-3-regulated protein (NFIL3).	[31]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Nuclear factor interleukin-3-regulated protein (NFIL3).	[44]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Nuclear factor interleukin-3-regulated protein (NFIL3).	[46]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid decreases the phosphorylation of Nuclear factor interleukin-3-regulated protein (NFIL3).	[52]

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