Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0GGRDO)

• DOT Name: Squalene monooxygenase (SQLE)
• Synonyms: EC 1.14.14.17; Squalene epoxidase; SE
• Gene Name: SQLE
• UniProt ID: ERG1_HUMAN
• PDB ID: 6C6N; 6C6P; 6C6R
• EC Number: 1.14.14.17
• Pfam ID: PF13450 ; PF08491
• Sequence:
  MWTFLGIATFTYFYKKFGDFITLANREVLLCVLVFLSLGLVLSYRCRHRNGGLLGRQQSG
  SQFALFSDILSGLPFIGFFWAKSPPESENKEQLEARRRRKGTNISETSLIGTAACTSTSS
  QNDPEVIIVGAGVLGSALAAVLSRDGRKVTVIERDLKEPDRIVGEFLQPGGYHVLKDLGL
  GDTVEGLDAQVVNGYMIHDQESKSEVQIPYPLSENNQVQSGRAFHHGRFIMSLRKAAMAE
  PNAKFIEGVVLQLLEEDDVVMGVQYKDKETGDIKELHAPLTVVADGLFSKFRKSLVSNKV
  SVSSHFVGFLMKNAPQFKANHAELILANPSPVLIYQISSSETRVLVDIRGEMPRNLREYM
  VEKIYPQIPDHLKEPFLEATDNSHLRSMPASFLPPSSVKKRGVLLLGDAYNMRHPLTGGG
  MTVAFKDIKLWRKLLKGIPDLYDDAAIFEAKKSFYWARKTSHSFVVNILAQALYELFSAT
  DDSLHQLRKACFLYFKLGGECVAGPVGLLSVLSPNPLVLIGHFFAVAIYAVYFCFKSEPW
  ITKPRALLSSGAVLYKACSVIFPLIYSEMKYMVH
• Function: Catalyzes the stereospecific oxidation of squalene to (S)-2,3-epoxysqualene, and is considered to be a rate-limiting enzyme in steroid biosynthesis.
• Tissue Specificity: Detected in liver (at protein level).
• KEGG Pathway:
  Steroid biosynthesis (hsa00100)
  Metabolic pathways (hsa01100)
• Reactome Pathway:
  Activation of gene expression by SREBF (SREBP) (R-HSA-2426168)
  Cholesterol biosynthesis (R-HSA-191273)
• BioCyc Pathway: MetaCyc:HS02595-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Temozolomide	DMKECZD	Approved	Squalene monooxygenase (SQLE) affects the response to substance of Temozolomide.	[35]
DTI-015	DMXZRW0	Approved	Squalene monooxygenase (SQLE) affects the response to substance of DTI-015.	[35]

38 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Squalene monooxygenase (SQLE).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Squalene monooxygenase (SQLE).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Squalene monooxygenase (SQLE).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Squalene monooxygenase (SQLE).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Squalene monooxygenase (SQLE).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Squalene monooxygenase (SQLE).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Squalene monooxygenase (SQLE).	[7]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Squalene monooxygenase (SQLE).	[8]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Squalene monooxygenase (SQLE).	[9]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Squalene monooxygenase (SQLE).	[10]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Squalene monooxygenase (SQLE).	[11]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Squalene monooxygenase (SQLE).	[12]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Squalene monooxygenase (SQLE).	[5]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Squalene monooxygenase (SQLE).	[13]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Squalene monooxygenase (SQLE).	[14]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Squalene monooxygenase (SQLE).	[15]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Squalene monooxygenase (SQLE).	[16]
Fluoxetine	DM3PD2C	Approved	Fluoxetine increases the expression of Squalene monooxygenase (SQLE).	[18]
Racecadotril	DMFOTZ7	Approved	Racecadotril increases the expression of Squalene monooxygenase (SQLE).	[19]
Isoflavone	DM7U58J	Phase 4	Isoflavone affects the expression of Squalene monooxygenase (SQLE).	[20]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Squalene monooxygenase (SQLE).	[11]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Squalene monooxygenase (SQLE).	[21]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Squalene monooxygenase (SQLE).	[21]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Squalene monooxygenase (SQLE).	[23]
GSK618334	DMJPXZ4	Phase 1	GSK618334 increases the expression of Squalene monooxygenase (SQLE).	[24]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Squalene monooxygenase (SQLE).	[25]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the expression of Squalene monooxygenase (SQLE).	[4]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Squalene monooxygenase (SQLE).	[26]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Squalene monooxygenase (SQLE).	[21]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Squalene monooxygenase (SQLE).	[27]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Squalene monooxygenase (SQLE).	[28]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Squalene monooxygenase (SQLE).	[29]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Squalene monooxygenase (SQLE).	[30]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride decreases the expression of Squalene monooxygenase (SQLE).	[31]
Chlorpyrifos	DMKPUI6	Investigative	Chlorpyrifos increases the expression of Squalene monooxygenase (SQLE).	[19]
PP-242	DM2348V	Investigative	PP-242 decreases the expression of Squalene monooxygenase (SQLE).	[32]
Rutin	DMEHRAJ	Investigative	Rutin increases the expression of Squalene monooxygenase (SQLE).	[33]
Linalool	DMGZQ5P	Investigative	Linalool increases the expression of Squalene monooxygenase (SQLE).	[34]

2 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Simvastatin	DM30SGU	Approved	Simvastatin decreases the degradation of Squalene monooxygenase (SQLE).	[17]
ANW-32821	DMMJOZD	Phase 2	ANW-32821 increases the degradation of Squalene monooxygenase (SQLE).	[17]

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 increases the methylation of Squalene monooxygenase (SQLE).	[22]

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