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Revision as of 14:40, 2 December 2010 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Script assisted update of identifiers from ChemSpider, CommonChemistry and FDA for the Chem/Drugbox validation project - Updated: InChI1->InChI StdInChI StdInChIKey SMILES1.← Previous edit Latest revision as of 19:39, 26 March 2024 edit undoCitation bot (talk | contribs)Bots5,416,881 edits Altered doi-access. | Use this bot. Report bugs. | Suggested by Jay8g | Category:CS1 maint: unflagged free DOI | #UCB_Category 79/132 
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{{chembox {{Chembox
| Verifiedfields = changed
⚫ |ImageFile=Lactacystin.svg
| Watchedfields = changed
⚫ |ImageSize=
| verifiedrevid = 400128403
⚫ |IUPACName=(2''R'')-2-(acetylamino)-3--4-methyl-5-oxopyrrolidin-2-yl}<br>carbonyl)sulfanyl]propanoic acid
⚫ | ImageFile = Lactacystin.svg
|OtherNames=
| ImageFile_Ref = {{chemboximage|correct|??}}
⚫ |Section1= {{Chembox Identifiers
⚫ | ImageSize = 244
⚫ | InChI = 1/C15H24N2O7S/c1-6(2)10(19)15(11(20)7(3)12(21)17-15)14(24)25-5-9(13(22)23)16-8(4)18/h6-7,9-11,19-20H,5H2,1-4H3,(H,16,18)(H,17,21)(H,22,23)/t7-,9+,10-,11+,15-/m1/s1
| ImageName = Stereo skeletal formula of lactacystin ((2''R'')-2-amid, (2''R'',3''S'',4''R'')-3-hydrox,-2-((1''S'')-1-hydrox)prop,-4-meth)
⚫ | SystematicName = (2''R'')-2-Acetamido-3-({(2''R'',3''S'',4''R'')-3-hydroxy-2--4-methyl-5-oxopyrrolidine-2-carbonyl}sulfanyl)propanoic acid
⚫ |Section1={{Chembox Identifiers
⚫ | CASNo = 133343-34-7
| CASNo_Ref = {{cascite|correct|??}}
⚫ | PubChem = 3870
| PubChem1 =
| PubChem1_Comment = <small>-2-((1''S'')-1-hydrox)prop</small>
| PubChem2 = 45039639
| PubChem2_Comment = <small>(3''S'',4''R'')-3-hydrox,-2-((1''R'')-1-hydrox)prop,-4-meth</small>
| PubChem3 = 46782036
| PubChem3_Comment = <small>(2''R'')-2-amid, (3''S'',4''R'')-3-hydrox,-2-((1''R'')-1-hydrox)prop,-4-meth</small>
| PubChem4 = 3034764
| PubChem4_Comment = <small>(2''R'')-2-amid, (3''S'',4''R'')-3-hydrox,-2-((1''S'')-1-hydrox)prop,-4-meth</small>
| ChemSpiderID = 3735
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID1 = 2299173
| ChemSpiderID1_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID1_Comment = <small>(2''R'')-2-amid, (3''S'',4''R'')-3-hydrox,-2-((1''S'')-1-hydrox)prop,-4-meth</small>
| MeSHName = Lactacystin
| ChEBI_Ref = {{ebicite|changed|EBI}}
| ChEBI = 52722
| ChEMBL = 374308
| ChEMBL_Ref = {{ebicite|changed|EBI}}
⚫ | SMILES = CC(C)C(O)C1(NC(=O)C(C)C1O)C(=O)SCC(NC(C)=O)C(O)=O
| SMILES1 = CC(=O)NC(CSC(=O)C1(C(O)C(C)C)NC(=O)C(C)C1O)C(=O)O
⚫ | SMILES2 = OC1C(C)C(=O)NC1(C(=O)SCC(NC(C)=O)C(O)=O)C(O)C(C)C
⚫ | StdInChI = 1S/C15H24N2O7S/c1-6(2)10(19)15(11(20)7(3)12(21)17-15)14(24)25-5-9(13(22)23)16-8(4)18/h6-7,9-11,19-20H,5H2,1-4H3,(H,16,18)(H,17,21)(H,22,23)
| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
⚫ | InChI = 1/C15H24N2O7S/c1-6(2)10(19)15(11(20)7(3)12(21)17-15)14(24)25-5-9(13(22)23)16-8(4)18/h6-7,9-11,19-20H,5H2,1-4H3,(H,16,18)(H,17,21)(H,22,23)
⚫ | StdInChIKey = DAQAKHDKYAWHCG-UHFFFAOYSA-N
| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
| InChIKey = DAQAKHDKYAWHCG-WBMULXAQBF | InChIKey = DAQAKHDKYAWHCG-WBMULXAQBF
⚫ | StdInChI = 1S/C15H24N2O7S/c1-6(2)10(19)15(11(20)7(3)12(21)17-15)14(24)25-5-9(13(22)23)16-8(4)18/h6-7,9-11,19-20H,5H2,1-4H3,(H,16,18)(H,17,21)(H,22,23)/t7-,9+,10-,11+,15-/m1/s1
⚫ | StdInChIKey = DAQAKHDKYAWHCG-WBMULXAQSA-N
⚫ | SMILES1 = O1(C)C(=O)N1(C(=O)SC(NC(C)=O)C(O)=O)(O)(C)C
⚫ | CASNo=133343-34-7
| ChemSpiderID=21106450
⚫ | PubChem=6610292
| SMILES = O1(C)C(=O)N1(C(=O)SC(NC(C)=O)C(O)=O)(O)(C)C
⚫ | SMILES=CC(=O)N(CSC(=O)1((O)C(C)C)NC(=O)(C)1O)C(=O)O
⚫ }}
⚫ |Section2= {{Chembox Properties
⚫ | C=15|H=24|N=2|O=7|S=1
| MolarMass=
| Appearance=
| Density=
| MeltingPt=
| BoilingPt=
| Solubility=
⚫ }}
|Section3= {{Chembox Hazards
| MainHazards=
| FlashPt=
| Autoignition=
}}
}} }}
⚫ |Section2={{Chembox Properties
'''Lactacystin''' is an ] naturally ] by ] of the ] '']'' first described in 1991.<ref name="Omura">Omura S, Fujimoto T, Otoguro K, Matsuzaki K, Moriguchi R, Tanaka H, Sasaki Y. (1991). Lactacystin, a novel microbial metabolite, induces neuritogenesis of neuroblastoma cells: S. Omura, et al. ''J. Antibiot.'' 44(1):113-6.</ref> The first ] of lactacystin was developed by ] in 1992.<ref name="Corey">''"Total Synthesis of Lactacystin"'' Corey, E. J.; Reichard, G. A. '']'' '''1992''', ''114'', 10677.</ref> The molecule is most commonly used as in ] and ] laboratories as a selective inhibitor of the ].<ref name="Fenteany">Fenteany G, Standaert RF, Lane WS, Choi S, Corey EJ, Schreiber SL. (1995) Inhibition of proteasome activities and subunit-specific amino-terminal threonine modification by lactacystin. ''Science'' 268:726-731.</ref><ref name="Orlowski">Orlowski RZ. (1999). The role of the ubiquitin-proteasome pathway in apoptosis. ''Cell Death Differ'' 6: 303-313.</ref> The molecule is a ], or cyclic ]. A number of syntheses of this molecule have been published and there are no less than 1,300 references to this natural product in the literature.<ref name="Brennan">Christopher J. Brennan, Gerald Pattenden, Gwenaella Rescourio . (2003). Formal Synthesis of (+)-Lactacystin Based on a Novel Radical Cyclization of an -Ethynyl-Substituted Serine: C Brennan et al. ''Tetrahedron Lett'' 44 (2003) 49, 8757-8760.</ref>
⚫ | C=15 | H=24 | N=2 | O=7 | S=1
| LogP = 0.086
| pKa = 3.106
| pKb = 10.891
⚫ }}
⚫ }}


'''Lactacystin''' is an ] naturally ] by ] of the ] '']'' first identified as an inducer of neuritogenesis in neuroblastoma cells in 1991.<ref name="Omura">Omura S, Fujimoto T, Otoguro K, Matsuzaki K, Moriguchi R, Tanaka H, Sasaki Y. (1991). Lactacystin, a novel microbial metabolite, induces neuritogenesis of neuroblastoma cells: S. Omura, et al. ''J. Antibiot.'' 44(1):113-6.</ref> The target of lactacystin was subsequently found to be the ] on the basis of its affinity for certain catalytic subunits of the proteasome by Fenteany and co-workers in 1995.<ref name="Fenteany1">{{cite journal |vauthors=Fenteany G, Standaert RF, Lane WS, Choi S, Corey EJ, Schreiber SL |title=Inhibition of proteasome activities and subunit-specific amino-terminal threonine modification by lactacystin |journal=Science |volume=268 |issue=5211 |pages=726–31 |year=1995 |pmid=7732382 |doi=10.1126/science.7732382|bibcode=1995Sci...268..726F |s2cid=37779687 }}</ref> The proteasome is a protein complex responsible for the bulk of proteolysis in the cell, as well as proteolytic activation of certain protein substrates. Lactacystin was the first non-peptidic proteasome inhibitor discovered and is widely used as a research tool in biochemistry and cell biology. The transformation product of lactacystin clasto-lactacystin β-lactone (also known as omuralide) covalently modifies the amino-terminal threonine of specific catalytic subunits of the proteasome, a discovery that helped to establish the proteasome as a mechanistically novel class of protease: an amino-terminal ]. The molecule is commonly used in ] and ] laboratories as a selective inhibitor of the ].<ref name="Fenteany1">{{cite journal |vauthors=Fenteany G, Standaert RF, Lane WS, Choi S, Corey EJ, Schreiber SL |title=Inhibition of proteasome activities and subunit-specific amino-terminal threonine modification by lactacystin |journal=Science |volume=268 |issue=5211 |pages=726–31 |year=1995 |pmid=7732382 |doi=10.1126/science.7732382|bibcode=1995Sci...268..726F |s2cid=37779687 }}</ref><ref name="Fenteany2">{{cite journal |vauthors=Fenteany G, Schreiber SL |title=Lactacystin, proteasome function, and cell fate |journal=J. Biol. Chem. |volume=273 |issue=15 |pages=8545–8 |year=1998 |pmid= 9535824 |doi=10.1074/jbc.273.15.8545|doi-access= free}}</ref> The first ] of lactacystin was developed in 1992 by Corey and Reichard,<ref name="Corey">''"Total Synthesis of Lactacystin"'' Corey, E. J.; Reichard, G. A. '']'' '''1992''', ''114'', 10677.</ref> and a number of other syntheses of this molecule have also been published. There are more than 1,660 entries for lactacystin in ] as of January 2019.
⚫ ==References==
<references />


==See also==
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⚫ ==References==

{{Reflist}}
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