Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTE14XG)

• DTT Name: Squalene monooxygenase (SQLE)
• Synonyms: Squalene epoxidase; SQLE; SE; Oxidosqaulene cyclase
• Gene Name: SQLE
• DTT Type: Successful target; [1]
• Related Disease:
  Dermatophytosis [ICD-11: 1F28]
  Skin fungal infection disorder [ICD-11: EA60]
• BioChemical Class: Paired donor oxygen oxidoreductase
• UniProt ID: ERG1_HUMAN
• TTD ID: T93344
• EC Number: EC 1.14.14.17
• Sequence:
  MWTFLGIATFTYFYKKFGDFITLANREVLLCVLVFLSLGLVLSYRCRHRNGGLLGRQQSG
  SQFALFSDILSGLPFIGFFWAKSPPESENKEQLEARRRRKGTNISETSLIGTAACTSTSS
  QNDPEVIIVGAGVLGSALAAVLSRDGRKVTVIERDLKEPDRIVGEFLQPGGYHVLKDLGL
  GDTVEGLDAQVVNGYMIHDQESKSEVQIPYPLSENNQVQSGRAFHHGRFIMSLRKAAMAE
  PNAKFIEGVVLQLLEEDDVVMGVQYKDKETGDIKELHAPLTVVADGLFSKFRKSLVSNKV
  SVSSHFVGFLMKNAPQFKANHAELILANPSPVLIYQISSSETRVLVDIRGEMPRNLREYM
  VEKIYPQIPDHLKEPFLEATDNSHLRSMPASFLPPSSVKKRGVLLLGDAYNMRHPLTGGG
  MTVAFKDIKLWRKLLKGIPDLYDDAAIFEAKKSFYWARKTSHSFVVNILAQALYELFSAT
  DDSLHQLRKACFLYFKLGGECVAGPVGLLSVLSPNPLVLIGHFFAVAIYAVYFCFKSEPW
  ITKPRALLSSGAVLYKACSVIFPLIYSEMKYMVH
• Function: Catalyzes the first oxygenation step in sterol biosynthesis and is suggested to be one of the rate-limiting enzymes in this pathway.
• KEGG Pathway:
  Steroid biosynthesis (sce00100)
  Sesquiterpenoid and triterpenoid biosynthesis (sce00909)
  Metabolic pathways (sce01100)
  Biosynthesis of secondary metabolites (sce01110)
  Biosynthesis of antibiotics (sce01130)
• Reactome Pathway:
  Activation of gene expression by SREBF (SREBP) (R-HSA-2426168)
  Cholesterol biosynthesis (R-HSA-191273)
• BioCyc Pathway: MetaCyc:HS02595-MON

Molecular Interaction Atlas (MIA) of This DTT

2 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Naftifine	DMHVBG1	Dermatomycosis	EA60	Approved	[2], [3]
Tolnaftate	DM28MU7	Dermatophytosis	1F28.2	Approved	[1], [2]

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Epigallocatechin gallate	DMCGWBJ	Hepatic fibrosis	DB93.0	Phase 3	[4]

3 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
FR-194738	DMNACIV	Hypercholesterolaemia	5C80.0	Terminated	[5]
NB-598	DMJVTQN	N. A.	N. A.	Terminated	[6]
SDZ-87-469	DMBY6CQ	Coronary artery disease	BA80	Terminated	[1]

26 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
1(beta)-O-galloylpedunculagin	DMA15X9	Discovery agent	N.A.	Investigative	[4]
1,2,3,4,6-penta-O-galloyl-beta-D-glucose	DMTK650	Discovery agent	N.A.	Investigative	[4]
1,2,6-tri-O-galloyl-beta-D-glucose	DMWGN3F	Discovery agent	N.A.	Investigative	[4]
Allylamines	DMNFGRV	Discovery agent	N.A.	Investigative	[7]
Chebulinic acid	DMR8HKC	Discovery agent	N.A.	Investigative	[4]
CORILAGIN	DMAC698	Discovery agent	N.A.	Investigative	[4]
ELLAGIC ACID	DMX8BS5	Discovery agent	N.A.	Investigative	[4]
Ethylgallate	DMJ6PB8	Discovery agent	N.A.	Investigative	[4]
EUGENIIN	DMUA485	Discovery agent	N.A.	Investigative	[4]
FUROSIN	DMVT0JO	Discovery agent	N.A.	Investigative	[4]
GERANIIN	DMB5I03	Discovery agent	N.A.	Investigative	[4]
Green tea	DMQHJTF	Discovery agent	N.A.	Investigative	[6]
Mallotinic acid	DM9ECWN	Discovery agent	N.A.	Investigative	[4]
Mallotusinic acid	DMHX9P8	Discovery agent	N.A.	Investigative	[4]
N-cetylgallate	DM5KNCX	Discovery agent	N.A.	Investigative	[4]
N-dodecylgallate	DMV5RZM	Discovery agent	N.A.	Investigative	[4]
OCTYL_GALLATE	DMXLGUS	Discovery agent	N.A.	Investigative	[4]
Pedunculagin	DMKLRCX	Discovery agent	N.A.	Investigative	[4]
Procyanidin B-2 3,3'-di-O-gallate	DMTW82E	Discovery agent	N.A.	Investigative	[4]
Sanguiin H-6	DM9XV16	Discovery agent	N.A.	Investigative	[4]
Tellurium	DMGD0HT	Discovery agent	N.A.	Investigative	[6]
THEASINENSIN A	DMG6S2V	Discovery agent	N.A.	Investigative	[4]
Thiocarbamate	DMP7LJH	Discovery agent	N.A.	Investigative	[2]
Trisnorsqualene alcohol	DMQVH3J	Discovery agent	N.A.	Investigative	[4]
Trisnorsqualene cyclopropylamine	DM0G2IR	Discovery agent	N.A.	Investigative	[4]
Trisnorsqualene difluoromethylidene	DMQA7ZS	Discovery agent	N.A.	Investigative	[4]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Familial hypercholesterolemia	5A11	Whole blood	7.14E-03	0.45	2.51
Coronary artery disease	BA80-BA8Z	Peripheral blood	5.26E-02	0.19	1.16
Atopic dermatitis	EA90	Skin	2.61E-04	-0.65	-2.3

References

• [1] Effects of squalene epoxidase inhibitors on Candida albicans. Antimicrob Agents Chemother. 1992 Aug;36(8):1779-81.
• [2] Characterization of squalene epoxidase activity from the dermatophyte Trichophyton rubrum and its inhibition by terbinafine and other antimycotic agents. Antimicrob Agents Chemother. 1996 Feb;40(2):443-7.
• [3] Mode of action of anti-Candida drugs: focus on terconazole and other ergosterol biosynthesis inhibitors. Am J Obstet Gynecol. 1991 Oct;165(4 Pt 2):1193-9.
• [4] Ellagitannins and hexahydroxydiphenoyl esters as inhibitors of vertebrate squalene epoxidase. J Nat Prod. 2001 Aug;64(8):1010-4.
• [5] Synthesis and biological activity of a novel squalene epoxidase inhibitor, FR194738. Bioorg Med Chem Lett. 2004 Feb 9;14(3):633-7.
• [6] Squalene epoxidase as hypocholesterolemic drug target revisited. Prog Lipid Res. 2003 Jan;42(1):37-50.
• [7] Differential inhibition of fungal amd mammalian squalene epoxidases by the benzylamine SDZ SBA 586 in comparison with the allylamine terbinafine. Arch Biochem Biophys. 1997 Apr 15;340(2):265-9.