Target Information

Target General Infomation
Target ID
T56175
Former ID
TTDR00866
Target Name
Lanosterol synthase
Gene Name
LSS
Synonyms
2,3-epoxysqualene--lanosterol cyclase; OSC; Oxidosqualene cyclase; Oxidosqualene--lanosterol cyclase; LSS
Target Type
Discontinued
Disease Arteriosclerosis [ICD9: 440; ICD10: I70]
Function
Catalyzes the cyclization of (S)-2,3 oxidosqualene to lanosterol, a reaction that forms the sterol nucleus.
BioChemical Class
Intramolecular transferases
Target Validation
T56175
UniProt ID
P48449
EC Number
EC 5.4.99.7
Sequence
MTEGTCLRRRGGPYKTEPATDLGRWRLNCERGRQTWTYLQDERAGREQTGLEAYALGLDT
KNYFKDLPKAHTAFEGALNGMTFYVGLQAEDGHWTGDYGGPLFLLPGLLITCHVARIPLP
AGYREEIVRYLRSVQLPDGGWGLHIEDKSTVFGTALNYVSLRILGVGPDDPDLVRARNIL
HKKGGAVAIPSWGKFWLAVLNVYSWEGLNTLFPEMWLFPDWAPAHPSTLWCHCRQVYLPM
SYCYAVRLSAAEDPLVQSLRQELYVEDFASIDWLAQRNNVAPDELYTPHSWLLRVVYALL
NLYEHHHSAHLRQRAVQKLYEHIVADDRFTKSISIGPISKTINMLVRWYVDGPASTAFQE
HVSRIPDYLWMGLDGMKMQGTNGSQIWDTAFAIQALLEAGGHHRPEFSSCLQKAHEFLRL
SQVPDNPPDYQKYYRQMRKGGFSFSTLDCGWIVSDCTAEALKAVLLLQEKCPHVTEHIPR
ERLCDAVAVLLNMRNPDGGFATYETKRGGHLLELLNPSEVFGDIMIDYTYVECTSAVMQA
LKYFHKRFPEHRAAEIRETLTQGLEFCRRQQRADGSWEGSWGVCFTYGTWFGLEAFACMG
QTYRDGTACAEVSRACDFLLSRQMADGGWGEDFESCEERRYLQSAQSQIHNTCWAMMGLM
AVRHPDIEAQERGVRCLLEKQLPNGDWPQENIAGVFNKSCAISYTSYRNIFPIWALGRFS
QLYPERALAGHP
Drugs and Mode of Action
Drug(s) BIBB-515 Drug Info Terminated Arteriosclerosis [534359]
BIBX-79 Drug Info Terminated Arteriosclerosis [534217]
Ro48-8071 Drug Info Terminated Discovery agent [541815], [546720]
ZD-9720 Drug Info Terminated Arteriosclerosis [526088]
Inhibitor 29-methylidene-2,3-oxidosqualene Drug Info [534308]
B-Octylglucoside Drug Info [551393]
compound 1 Drug Info [531884]
compound 1 (Gotteland et al., 1997) Drug Info [543630]
compound 10 Drug Info [531884]
compound 3 Drug Info [534308]
compound 3 Drug Info [531884]
compound 4 Drug Info [531884]
compound 4 Drug Info [534308]
compound 4a (Marquart et al., 1994) Drug Info [543630]
compound 4b (Marquart et al., 1994) Drug Info [543630]
compound 5 Drug Info [531884]
compound 6 Drug Info [531884]
compound 7 Drug Info [531884]
compound 8 Drug Info [531884]
compound 9 Drug Info [531884]
Lanosterol Drug Info [551393]
R048-8071 Drug Info [551393]
Ro48-8071 Drug Info [535462]
Tetradecane Drug Info [551393]
[3-(Biphenyl-4-yloxy)-propyl]-dimethyl-amine Drug Info [526789]
Modulator BIBB-515 Drug Info [526088], [534359]
BIBX-79 Drug Info [526088], [534217]
ZD-9720 Drug Info [526088]
Pathways
BioCyc Pathway Cholesterol biosynthesis II (via 24,25-dihydrolanosterol)
Cholesterol biosynthesis III (via desmosterol)
Cholesterol biosynthesis I
Superpathway of cholesterol biosynthesis
Lanosterol biosynthesis
KEGG Pathway Steroid biosynthesis
Metabolic pathways
Biosynthesis of antibiotics
PANTHER Pathway Cholesterol biosynthesis
PathWhiz Pathway Steroid Biosynthesis
Reactome Cholesterol biosynthesis
Activation of gene expression by SREBF (SREBP)
WikiPathways Activation of Gene Expression by SREBP (SREBF)
SREBP signalling
Cholesterol Biosynthesis
Cholesterol biosynthesis
References
Ref 526088Toxicologic lesions associated with two related inhibitors of oxidosqualene cyclase in the dog and mouse. Toxicol Pathol. 2001 Mar-Apr;29(2):174-9.
Ref 534217Effects 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.
Ref 534359Effects 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.
Ref 541815(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6710).
Ref 546720Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800009903)
Ref 526088Toxicologic lesions associated with two related inhibitors of oxidosqualene cyclase in the dog and mouse. Toxicol Pathol. 2001 Mar-Apr;29(2):174-9.
Ref 526789J Med Chem. 2003 Sep 25;46(20):4240-3.Oxidosqualene cyclase inhibitors as antimicrobial agents.
Ref 531884Cytotoxic effects of combination of oxidosqualene cyclase inhibitors with atorvastatin in human cancer cells. J Med Chem. 2012 Jun 14;55(11):4990-5002.
Ref 534217Effects 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.
Ref 534308Synthesis 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.
Ref 534359Effects 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.
Ref 535462Crystal structure of a squalene cyclase in complex with the potential anticholesteremic drug Ro48-8071. Chem Biol. 2002 May;9(5):639-45.
Ref 543630(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2434).
Ref 551393How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6.

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