Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKIE59S)

• DOT Name: Nuclear factor of activated T-cells 5 (NFAT5)
• Synonyms: NF-AT5; T-cell transcription factor NFAT5; Tonicity-responsive enhancer-binding protein; TonE-binding protein; TonEBP
• Gene Name: NFAT5
• Related Disease:
  Adult glioblastoma
  Chronic renal failure
  Arteriosclerosis
  Arthritis
  Atherosclerosis
  Autoimmune disease
  Breast carcinoma
  Cardiac disease
  Cocaine addiction
  Colitis
  Dermatomyositis
  Glioblastoma multiforme
  Glioma
  Hepatocellular carcinoma
  High blood pressure
  Hyperglycemia
  Immunodeficiency
  Intervertebral disc degeneration
  Knee osteoarthritis
  Late-onset Parkinson disease
  Leiomyoma
  leukaemia
  Leukemia
  Matthew-Wood syndrome
  Metastatic malignant neoplasm
  Myocardial infarction
  Myositis disease
  Neoplasm
  Neuralgia
  Non-insulin dependent diabetes
  Non-small-cell lung cancer
  Pancreatic cancer
  Polymyositis
  Type-1/2 diabetes
  Uterine fibroids
  Fetal growth restriction
  Hyperinsulinemia
  Hyperlipidemia
  Obesity
  Rheumatoid arthritis
  Type-1 diabetes
  Advanced cancer
  Breast cancer
  Diabetic kidney disease
  Keratoconjunctivitis sicca
  Melanoma
• UniProt ID: NFAT5_HUMAN
• PDB ID: 1IMH
• Pfam ID: PF16179 ; PF00554
• Sequence:
  MPSDFISLLSADLDLESPKSLYSRESVYDLLPKELQLPPSRETSVASMSQTSGGEAGSPP
  PAVVAADASSAPSSSSMGGACSSFTTSSSPTIYSTSVTDSKAMQVESCSSAVGVSNRGVS
  EKQLTSNTVQQHPSTPKRHTVLYISPPPEDLLDNSRMSCQDEGCGLESEQSCSMWMEDSP
  SNFSNMSTSSYNDNTEVPRKSRKRNPKQRPGVKRRDCEESNMDIFDADSAKAPHYVLSQL
  TTDNKGNSKAGNGTLENQKGTGVKKSPMLCGQYPVKSEGKELKIVVQPETQHRARYLTEG
  SRGSVKDRTQQGFPTVKLEGHNEPVVLQVFVGNDSGRVKPHGFYQACRVTGRNTTPCKEV
  DIEGTTVIEVGLDPSNNMTLAVDCVGILKLRNADVEARIGIAGSKKKSTRARLVFRVNIM
  RKDGSTLTLQTPSSPILCTQPAGVPEILKKSLHSCSVKGEEEVFLIGKNFLKGTKVIFQE
  NVSDENSWKSEAEIDMELFHQNHLIVKVPPYHDQHITLPVSVGIYVVTNAGRSHDVQPFT
  YTPDPAAAGALNVNVKKEISSPARPCSFEEAMKAMKTTGCNLDKVNIIPNALMTPLIPSS
  MIKSEDVTPMEVTAEKRSSTIFKTTKSVGSTQQTLENISNIAGNGSFSSPSSSHLPSENE
  KQQQIQPKAYNPETLTTIQTQDISQPGTFPAVSASSQLPNSDALLQQATQFQTRETQSRE
  ILQSDGTVVNLSQLTEASQQQQQSPLQEQAQTLQQQISSNIFPSPNSVSQLQNTIQQLQA
  GSFTGSTASGSSGSVDLVQQVLEAQQQLSSVLFSAPDGNENVQEQLSADIFQQVSQIQSG
  VSPGMFSSTEPTVHTRPDNLLPGRAESVHPQSENTLSNQQQQQQQQQQVMESSAAMVMEM
  QQSICQAAAQIQSELFPSTASANGNLQQSPVYQQTSHMMSALSTNEDMQMQCELFSSPPA
  VSGNETSTTTTQQVATPGTTMFQTSSSGDGEETGTQAKQIQNSVFQTMVQMQHSGDNQPQ
  VNLFSSTKSMMSVQNSGTQQQGNGLFQQGNEMMSLQSGNFLQQSSHSQAQLFHPQNPIAD
  AQNLSQETQGSLFHSPNPIVHSQTSTTSSEQMQPPMFHSQSTIAVLQGSSVPQDQQSTNI
  FLSQSPMNNLQTNTVAQEAFFAAPNSISPLQSTSNSEQQAAFQQQAPISHIQTPMLSQEQ
  AQPPQQGLFQPQVALGSLPPNPMPQSQQGTMFQSQHSIVAMQSNSPSQEQQQQQQQQQQQ
  QQQQQQSILFSNQNTMATMASPKQPPPNMIFNPNQNPMANQEQQNQSIFHQQSNMAPMNQ
  EQQPMQFQSQSTVSSLQNPGPTQSESSQTPLFHSSPQIQLVQGSPSSQEQQVTLFLSPAS
  MSALQTSINQQDMQQSPLYSPQNNMPGIQGATSSPQPQATLFHNTAGGTMNQLQNSPGSS
  QQTSGMFLFGIQNNCSQLLTSGPATLPDQLMAISQPGQPQNEGQPPVTTLLSQQMPENSP
  LASSINTNQNIEKIDLLVSLQNQGNNLTGSF
• Function: Transcription factor involved, among others, in the transcriptional regulation of osmoprotective and inflammatory genes. Binds the DNA consensus sequence 5'-[ACT][AG]TGGAAA[CAT]A[TA][ATC][CA][ATG][GT][GAC][CG][CT]-3'. Mediates the transcriptional response to hypertonicity. Positively regulates the transcription of LCN2 and S100A4 genes; optimal transactivation of these genes requires the presence of DDX5/DDX17. Also involved in the DNA damage response by preventing formation of R-loops; R-loops are composed of a DNA:RNA hybrid and the associated non-template single-stranded DNA.
• Tissue Specificity: Widely expressed, with highest levels in skeletal muscle, brain, heart and peripheral blood leukocytes.

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]
Chronic renal failure	DISGG7K6	Definitive	Genetic Variation	[2]
Arteriosclerosis	DISK5QGC	Strong	Altered Expression	[3]
Arthritis	DIST1YEL	Strong	Biomarker	[4]
Atherosclerosis	DISMN9J3	Strong	Altered Expression	[3]
Autoimmune disease	DISORMTM	Strong	Biomarker	[5]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[6]
Cardiac disease	DISVO1I5	Strong	Biomarker	[7]
Cocaine addiction	DISHTRXG	Strong	Genetic Variation	[8]
Colitis	DISAF7DD	Strong	Altered Expression	[9]
Dermatomyositis	DIS50C5O	Strong	Altered Expression	[10]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[1]
Glioma	DIS5RPEH	Strong	Altered Expression	[11]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[12]
High blood pressure	DISY2OHH	Strong	Genetic Variation	[13]
Hyperglycemia	DIS0BZB5	Strong	Altered Expression	[14]
Immunodeficiency	DIS093I0	Strong	Biomarker	[15]
Intervertebral disc degeneration	DISG3AIM	Strong	Biomarker	[16]
Knee osteoarthritis	DISLSNBJ	Strong	Genetic Variation	[17]
Late-onset Parkinson disease	DIS9IOUI	Strong	Altered Expression	[18]
Leiomyoma	DISLDDFN	Strong	Altered Expression	[19]
leukaemia	DISS7D1V	Strong	Biomarker	[20]
Leukemia	DISNAKFL	Strong	Biomarker	[20]
Matthew-Wood syndrome	DISA7HR7	Strong	Altered Expression	[21]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[6]
Myocardial infarction	DIS655KI	Strong	Biomarker	[22]
Myositis disease	DISCIXF0	Strong	Altered Expression	[10]
Neoplasm	DISZKGEW	Strong	Biomarker	[12]
Neuralgia	DISWO58J	Strong	Biomarker	[23]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[24]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[25]
Pancreatic cancer	DISJC981	Strong	Altered Expression	[21]
Polymyositis	DIS5DHFP	Strong	Biomarker	[10]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[26]
Uterine fibroids	DISBZRMJ	Strong	Altered Expression	[19]
Fetal growth restriction	DIS5WEJ5	moderate	Altered Expression	[27]
Hyperinsulinemia	DISIDWT6	moderate	Biomarker	[28]
Hyperlipidemia	DIS61J3S	moderate	Biomarker	[28]
Obesity	DIS47Y1K	moderate	Biomarker	[28]
Rheumatoid arthritis	DISTSB4J	moderate	Biomarker	[5]
Type-1 diabetes	DIS7HLUB	Disputed	Biomarker	[29]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[30]
Breast cancer	DIS7DPX1	Limited	Biomarker	[6]
Diabetic kidney disease	DISJMWEY	Limited	Biomarker	[26]
Keratoconjunctivitis sicca	DISNOENH	Limited	Altered Expression	[31]
Melanoma	DIS1RRCY	Limited	Biomarker	[30]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Temozolomide	DMKECZD	Approved	Nuclear factor of activated T-cells 5 (NFAT5) affects the response to substance of Temozolomide.	[57]
DTI-015	DMXZRW0	Approved	Nuclear factor of activated T-cells 5 (NFAT5) affects the response to substance of DTI-015.	[57]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Uric acid	DMA1MKT	Investigative	Nuclear factor of activated T-cells 5 (NFAT5) affects the abundance of Uric acid.	[58]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Nuclear factor of activated T-cells 5 (NFAT5).	[32]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Nuclear factor of activated T-cells 5 (NFAT5).	[48]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Nuclear factor of activated T-cells 5 (NFAT5).	[50]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Nuclear factor of activated T-cells 5 (NFAT5).	[50]

25 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 Nuclear factor of activated T-cells 5 (NFAT5).	[33]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Nuclear factor of activated T-cells 5 (NFAT5).	[34]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Nuclear factor of activated T-cells 5 (NFAT5).	[35]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Nuclear factor of activated T-cells 5 (NFAT5).	[33]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Nuclear factor of activated T-cells 5 (NFAT5).	[33]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Nuclear factor of activated T-cells 5 (NFAT5).	[36]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Nuclear factor of activated T-cells 5 (NFAT5).	[37]
Marinol	DM70IK5	Approved	Marinol increases the expression of Nuclear factor of activated T-cells 5 (NFAT5).	[38]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Nuclear factor of activated T-cells 5 (NFAT5).	[39]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Nuclear factor of activated T-cells 5 (NFAT5).	[40]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate increases the expression of Nuclear factor of activated T-cells 5 (NFAT5).	[41]
Sodium chloride	DMM3950	Approved	Sodium chloride increases the expression of Nuclear factor of activated T-cells 5 (NFAT5).	[42]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Nuclear factor of activated T-cells 5 (NFAT5).	[43]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Nuclear factor of activated T-cells 5 (NFAT5).	[44]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Nuclear factor of activated T-cells 5 (NFAT5).	[45]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Nuclear factor of activated T-cells 5 (NFAT5).	[39]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of Nuclear factor of activated T-cells 5 (NFAT5).	[46]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Nuclear factor of activated T-cells 5 (NFAT5).	[47]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Nuclear factor of activated T-cells 5 (NFAT5).	[49]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Nuclear factor of activated T-cells 5 (NFAT5).	[51]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Nuclear factor of activated T-cells 5 (NFAT5).	[52]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Nuclear factor of activated T-cells 5 (NFAT5).	[53]
geraniol	DMS3CBD	Investigative	geraniol increases the expression of Nuclear factor of activated T-cells 5 (NFAT5).	[54]
OXYBENZONE	DMMZYX6	Investigative	OXYBENZONE increases the expression of Nuclear factor of activated T-cells 5 (NFAT5).	[55]
Maleic Acid	DM4L0R7	Investigative	Maleic Acid increases the expression of Nuclear factor of activated T-cells 5 (NFAT5).	[56]

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