Target Information
| Target General Infomation | |||||
|---|---|---|---|---|---|
| Target ID |
T56175
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| Former ID |
TTDR00866
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| Target Name |
Lanosterol synthase
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| Gene Name |
LSS
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| Synonyms |
2,3-epoxysqualene--lanosterol cyclase; OSC; Oxidosqualene cyclase; Oxidosqualene--lanosterol cyclase; LSS
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| Target Type |
Discontinued
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| Disease | Arteriosclerosis [ICD9: 440; ICD10: I70] | ||||
| Function |
Catalyzes the cyclization of (S)-2,3 oxidosqualene to lanosterol, a reaction that forms the sterol nucleus.
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| BioChemical Class |
Intramolecular transferases
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| Target Validation |
T56175
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| UniProt ID | |||||
| EC Number |
EC 5.4.99.7
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| Sequence |
MTEGTCLRRRGGPYKTEPATDLGRWRLNCERGRQTWTYLQDERAGREQTGLEAYALGLDT
KNYFKDLPKAHTAFEGALNGMTFYVGLQAEDGHWTGDYGGPLFLLPGLLITCHVARIPLP AGYREEIVRYLRSVQLPDGGWGLHIEDKSTVFGTALNYVSLRILGVGPDDPDLVRARNIL HKKGGAVAIPSWGKFWLAVLNVYSWEGLNTLFPEMWLFPDWAPAHPSTLWCHCRQVYLPM SYCYAVRLSAAEDPLVQSLRQELYVEDFASIDWLAQRNNVAPDELYTPHSWLLRVVYALL NLYEHHHSAHLRQRAVQKLYEHIVADDRFTKSISIGPISKTINMLVRWYVDGPASTAFQE HVSRIPDYLWMGLDGMKMQGTNGSQIWDTAFAIQALLEAGGHHRPEFSSCLQKAHEFLRL SQVPDNPPDYQKYYRQMRKGGFSFSTLDCGWIVSDCTAEALKAVLLLQEKCPHVTEHIPR ERLCDAVAVLLNMRNPDGGFATYETKRGGHLLELLNPSEVFGDIMIDYTYVECTSAVMQA LKYFHKRFPEHRAAEIRETLTQGLEFCRRQQRADGSWEGSWGVCFTYGTWFGLEAFACMG QTYRDGTACAEVSRACDFLLSRQMADGGWGEDFESCEERRYLQSAQSQIHNTCWAMMGLM AVRHPDIEAQERGVRCLLEKQLPNGDWPQENIAGVFNKSCAISYTSYRNIFPIWALGRFS QLYPERALAGHP |
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| Drugs and Mode of Action | |||||
| Drug(s) | BIBB-515 | Drug Info | Terminated | Arteriosclerosis | [1] |
| BIBX-79 | Drug Info | Terminated | Arteriosclerosis | [2] | |
| Ro48-8071 | Drug Info | Terminated | Discovery agent | [3], [4] | |
| ZD-9720 | Drug Info | Terminated | Arteriosclerosis | [5] | |
| Inhibitor | 29-methylidene-2,3-oxidosqualene | Drug Info | [6] | ||
| B-Octylglucoside | Drug Info | [7] | |||
| compound 1 | Drug Info | [8] | |||
| compound 1 (Gotteland et al., 1997) | Drug Info | [9] | |||
| compound 10 | Drug Info | [8] | |||
| compound 3 | Drug Info | [6] | |||
| compound 3 | Drug Info | [8] | |||
| compound 4 | Drug Info | [8] | |||
| compound 4 | Drug Info | [6] | |||
| compound 4a (Marquart et al., 1994) | Drug Info | [9] | |||
| compound 4b (Marquart et al., 1994) | Drug Info | [9] | |||
| compound 5 | Drug Info | [8] | |||
| compound 6 | Drug Info | [8] | |||
| compound 7 | Drug Info | [8] | |||
| compound 8 | Drug Info | [8] | |||
| compound 9 | Drug Info | [8] | |||
| Lanosterol | Drug Info | [7] | |||
| R048-8071 | Drug Info | [7] | |||
| Ro48-8071 | Drug Info | [10] | |||
| Tetradecane | Drug Info | [7] | |||
| [3-(Biphenyl-4-yloxy)-propyl]-dimethyl-amine | Drug Info | [11] | |||
| Modulator | BIBB-515 | Drug Info | [5], [1] | ||
| BIBX-79 | Drug Info | [5], [2] | |||
| ZD-9720 | Drug Info | [5] | |||
| 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 1 | 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. | ||||
| REF 2 | 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. | ||||
| REF 3 | (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 4 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800009903) | ||||
| REF 5 | Toxicologic lesions associated with two related inhibitors of oxidosqualene cyclase in the dog and mouse. Toxicol Pathol. 2001 Mar-Apr;29(2):174-9. | ||||
| REF 6 | 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. | ||||
| REF 7 | How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | ||||
| REF 8 | Cytotoxic effects of combination of oxidosqualene cyclase inhibitors with atorvastatin in human cancer cells. J Med Chem. 2012 Jun 14;55(11):4990-5002. | ||||
| REF 9 | (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 10 | Crystal structure of a squalene cyclase in complex with the potential anticholesteremic drug Ro48-8071. Chem Biol. 2002 May;9(5):639-45. | ||||
| REF 11 | J Med Chem. 2003 Sep 25;46(20):4240-3.Oxidosqualene cyclase inhibitors as antimicrobial agents. | ||||
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