Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT7O8ZA)

• DTT Name: Lanosterol synthase (LSS)
• Synonyms: Oxidosqualene--lanosterol cyclase; Oxidosqualene cyclase; OSC; LSS; 2,3-epoxysqualene--lanosterol cyclase
• Gene Name: LSS
• DTT Type: Literature-reported target; [1]
• BioChemical Class: Intramolecular transferases
• UniProt ID: ERG7_HUMAN
• TTD ID: T56175
• EC Number: EC 5.4.99.7
• Sequence:
  MTEGTCLRRRGGPYKTEPATDLGRWRLNCERGRQTWTYLQDERAGREQTGLEAYALGLDT
  KNYFKDLPKAHTAFEGALNGMTFYVGLQAEDGHWTGDYGGPLFLLPGLLITCHVARIPLP
  AGYREEIVRYLRSVQLPDGGWGLHIEDKSTVFGTALNYVSLRILGVGPDDPDLVRARNIL
  HKKGGAVAIPSWGKFWLAVLNVYSWEGLNTLFPEMWLFPDWAPAHPSTLWCHCRQVYLPM
  SYCYAVRLSAAEDPLVQSLRQELYVEDFASIDWLAQRNNVAPDELYTPHSWLLRVVYALL
  NLYEHHHSAHLRQRAVQKLYEHIVADDRFTKSISIGPISKTINMLVRWYVDGPASTAFQE
  HVSRIPDYLWMGLDGMKMQGTNGSQIWDTAFAIQALLEAGGHHRPEFSSCLQKAHEFLRL
  SQVPDNPPDYQKYYRQMRKGGFSFSTLDCGWIVSDCTAEALKAVLLLQEKCPHVTEHIPR
  ERLCDAVAVLLNMRNPDGGFATYETKRGGHLLELLNPSEVFGDIMIDYTYVECTSAVMQA
  LKYFHKRFPEHRAAEIRETLTQGLEFCRRQQRADGSWEGSWGVCFTYGTWFGLEAFACMG
  QTYRDGTACAEVSRACDFLLSRQMADGGWGEDFESCEERRYLQSAQSQIHNTCWAMMGLM
  AVRHPDIEAQERGVRCLLEKQLPNGDWPQENIAGVFNKSCAISYTSYRNIFPIWALGRFS
  QLYPERALAGHP
• Function: Catalyzes the cyclization of (S)-2,3 oxidosqualene to lanosterol, a reaction that forms the sterol nucleus.
• KEGG Pathway:
  Steroid biosynthesis (hsa00100)
  Metabolic pathways (hsa01100)
  Biosynthesis of antibiotics (hsa01130)
• Reactome Pathway:
  Activation of gene expression by SREBF (SREBP) (R-HSA-2426168)
  Cholesterol biosynthesis (R-HSA-191273)
• BioCyc Pathway: MetaCyc:HS08480-MON

Molecular Interaction Atlas (MIA) of This DTT

3 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BIBB-515	DM6QT9P	Arteriosclerosis	BD40	Terminated	[2]
BIBX-79	DMRXWCO	Arteriosclerosis	BD40	Terminated	[1]
ZD-9720	DMFV47R	Arteriosclerosis	BD40	Terminated	[3]

11 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
29-methylidene-2,3-oxidosqualene	DMUQAP7	Discovery agent	N.A.	Investigative	[4]
B-Octylglucoside	DMMO75G	Discovery agent	N.A.	Investigative	[5]
Lanosterol	DMHN74V	Discovery agent	N.A.	Investigative	[5]
PMID22533316C1	DMYEMWB	Discovery agent	N.A.	Investigative	[6]
PMID22533316C3	DMOZG0A	Discovery agent	N.A.	Investigative	[6]
PMID22533316C4	DMW3UHO	Discovery agent	N.A.	Investigative	[6]
PMID9003518C3	DM1I578	Discovery agent	N.A.	Investigative	[4]
PMID9003518C4	DMYE64O	Discovery agent	N.A.	Investigative	[4]
Ro48-8071	DMVGITD	Discovery agent	N.A.	Investigative	[5]
Tetradecane	DMK8P61	Discovery agent	N.A.	Investigative	[5]
[3-(Biphenyl-4-yloxy)-propyl]-dimethyl-amine	DMRBJ4V	Discovery agent	N.A.	Investigative	[7]

References

• [1] Effects of a novel 2,3-oxidosqualene cyclase inhibitor on the regulation of cholesterol biosynthesis in HepG2 cells. J Lipid Res. 1996 Jan;37(1):148-58.
• [2] Effects of a novel 2,3-oxidosqualene cyclase inhibitor on cholesterol biosynthesis and lipid metabolism in vivo. J Lipid Res. 1997 Mar;38(3):564-75.
• [3] Toxicologic lesions associated with two related inhibitors of oxidosqualene cyclase in the dog and mouse. Toxicol Pathol. 2001 Mar-Apr;29(2):174-9.
• [4] Synthesis and inhibition studies of sulfur-substituted squalene oxide analogues as mechanism-based inhibitors of 2,3-oxidosqualene-lanosterol cyclase. J Med Chem. 1997 Jan 17;40(2):201-9.
• [5] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [6] Cytotoxic effects of combination of oxidosqualene cyclase inhibitors with atorvastatin in human cancer cells. J Med Chem. 2012 Jun 14;55(11):4990-5002.
• [7] Oxidosqualene cyclase inhibitors as antimicrobial agents. J Med Chem. 2003 Sep 25;46(20):4240-3.