Details of Drug Off-Target (DOT)

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

• DOT Name: Sestrin-1 (SESN1)
• Synonyms: EC 1.11.1.-; p53-regulated protein PA26
• Gene Name: SESN1
• Related Disease:
  Chronic fatigue syndrome
  Endometrial cancer
  Endometrial carcinoma
  Head and neck cancer
  Head and neck carcinoma
  Non-insulin dependent diabetes
• UniProt ID: SESN1_HUMAN
• EC Number: 1.11.1.-
• Pfam ID: PF04636
• Sequence:
  MRLAAAANEAYTAPLAVSGLLGCKQCGGGRDQDEELGIRIPRPLGQGPSRFIPEKEILQV
  GSEDAQMHALFADSFAALGRLDNITLVMVFHPQYLESFLKTQHYLLQMDGPLPLHYRHYI
  GIMAAARHQCSYLVNLHVNDFLHVGGDPKWLNGLENAPQKLQNLGELNKVLAHRPWLITK
  EHIEGLLKAEEHSWSLAELVHAVVLLTHYHSLASFTFGCGISPEIHCDGGHTFRPPSVSN
  YCICDITNGNHSVDEMPVNSAENVSVSDSFFEVEALMEKMRQLQECRDEEEASQEEMASR
  FEIEKRESMFVFSSDDEEVTPARAVSRHFEDTSYGYKDFSRHGMHVPTFRVQDYCWEDHG
  YSLVNRLYPDVGQLIDEKFHIAYNLTYNTMAMHKDVDTSMLRRAIWNYIHCMFGIRYDDY
  DYGEINQLLDRSFKVYIKTVVCTPEKVTKRMYDSFWRQFKHSEKVHVNLLLIEARMQAEL
  LYALRAITRYMT
• Function: Functions as an intracellular leucine sensor that negatively regulates the TORC1 signaling pathway through the GATOR complex. In absence of leucine, binds the GATOR subcomplex GATOR2 and prevents TORC1 signaling. Binding of leucine to SESN2 disrupts its interaction with GATOR2 thereby activating the TORC1 signaling pathway. This stress-inducible metabolic regulator may also play a role in protection against oxidative and genotoxic stresses. May positively regulate the transcription by NFE2L2 of genes involved in the response to oxidative stress by facilitating the SQSTM1-mediated autophagic degradation of KEAP1. Moreover, may prevent the accumulation of reactive oxygen species (ROS) through the alkylhydroperoxide reductase activity born by the N-terminal domain of the protein. Was originally reported to contribute to oxidative stress resistance by reducing PRDX1. However, this could not be confirmed.
• Tissue Specificity: Widely expressed.
• KEGG Pathway:
  p53 sig.ling pathway (hsa04115)
  Longevity regulating pathway (hsa04211)
• Reactome Pathway:
  Amino acids regulate mTORC1 (R-HSA-9639288)
  KEAP1-NFE2L2 pathway (R-HSA-9755511)
  TP53 Regulates Metabolic Genes (R-HSA-5628897)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chronic fatigue syndrome	DIS34WJ5	Strong	Biomarker	[1]
Endometrial cancer	DISW0LMR	Strong	Biomarker	[2]
Endometrial carcinoma	DISXR5CY	Strong	Biomarker	[2]
Head and neck cancer	DISBPSQZ	Strong	Biomarker	[3]
Head and neck carcinoma	DISOU1DS	Strong	Biomarker	[3]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Altered Expression	[4]

2 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 Sestrin-1 (SESN1).	[5]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Sestrin-1 (SESN1).	[32]

39 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 Sestrin-1 (SESN1).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Sestrin-1 (SESN1).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Sestrin-1 (SESN1).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Sestrin-1 (SESN1).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Sestrin-1 (SESN1).	[10]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Sestrin-1 (SESN1).	[11]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Sestrin-1 (SESN1).	[12]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Sestrin-1 (SESN1).	[13]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Sestrin-1 (SESN1).	[14]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Sestrin-1 (SESN1).	[15]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Sestrin-1 (SESN1).	[15]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Sestrin-1 (SESN1).	[16]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Sestrin-1 (SESN1).	[17]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Sestrin-1 (SESN1).	[18]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Sestrin-1 (SESN1).	[19]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Sestrin-1 (SESN1).	[20]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Sestrin-1 (SESN1).	[21]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Sestrin-1 (SESN1).	[22]
Etoposide	DMNH3PG	Approved	Etoposide increases the expression of Sestrin-1 (SESN1).	[23]
Cidofovir	DMA13GD	Approved	Cidofovir increases the expression of Sestrin-1 (SESN1).	[19]
Ifosfamide	DMCT3I8	Approved	Ifosfamide increases the expression of Sestrin-1 (SESN1).	[19]
Capsaicin	DMGMF6V	Approved	Capsaicin increases the expression of Sestrin-1 (SESN1).	[24]
Colchicine	DM2POTE	Approved	Colchicine decreases the expression of Sestrin-1 (SESN1).	[23]
Hydroxyurea	DMOQVU9	Approved	Hydroxyurea increases the expression of Sestrin-1 (SESN1).	[23]
Adefovir dipivoxil	DMMAWY1	Approved	Adefovir dipivoxil increases the expression of Sestrin-1 (SESN1).	[19]
Adenine	DMZLHKJ	Approved	Adenine decreases the expression of Sestrin-1 (SESN1).	[23]
Isoflavone	DM7U58J	Phase 4	Isoflavone increases the expression of Sestrin-1 (SESN1).	[25]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Sestrin-1 (SESN1).	[26]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Sestrin-1 (SESN1).	[27]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Sestrin-1 (SESN1).	[28]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Sestrin-1 (SESN1).	[29]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Sestrin-1 (SESN1).	[30]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Sestrin-1 (SESN1).	[31]
Celastrol	DMWQIJX	Preclinical	Celastrol decreases the expression of Sestrin-1 (SESN1).	[33]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Sestrin-1 (SESN1).	[34]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Sestrin-1 (SESN1).	[35]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone decreases the expression of Sestrin-1 (SESN1).	[36]
Forskolin	DM6ITNG	Investigative	Forskolin decreases the expression of Sestrin-1 (SESN1).	[36]
Bilirubin	DMI0V4O	Investigative	Bilirubin decreases the expression of Sestrin-1 (SESN1).	[37]

References

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