lactacystin

{{Chembox

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 400128403

| ImageFile = Lactacystin.svg

| ImageFile_Ref = {{chemboximage|correct|??}}

| ImageSize = 244

| ImageName = Stereo skeletal formula of lactacystin ((2R)-2-amid, (2R,3S,4R)-3-hydrox,-2-((1S)-1-hydrox)prop,-4-meth)

| SystematicName = (2R)-2-Acetamido-3-({(2R,3S,4R)-3-hydroxy-2-[(1S)-1-hydroxy-2-methylpropyl]-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 = -2-((1S)-1-hydrox)prop

| PubChem2 = 45039639

| PubChem2_Comment = (3S,4R)-3-hydrox,-2-((1R)-1-hydrox)prop,-4-meth

| PubChem3 = 46782036

| PubChem3_Comment = (2R)-2-amid, (3S,4R)-3-hydrox,-2-((1R)-1-hydrox)prop,-4-meth

| PubChem4 = 3034764

| PubChem4_Comment = (2R)-2-amid, (3S,4R)-3-hydrox,-2-((1S)-1-hydrox)prop,-4-meth

| ChemSpiderID = 3735

| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}

| ChemSpiderID1 = 2299173

| ChemSpiderID1_Ref = {{chemspidercite|changed|chemspider}}

| ChemSpiderID1_Comment = (2R)-2-amid, (3S,4R)-3-hydrox,-2-((1S)-1-hydrox)prop,-4-meth

| 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

}}

|Section2={{Chembox Properties

| C=15 | H=24 | N=2 | O=7 | S=1

| LogP = 0.086

| pKa = 3.106

| pKb = 10.891

}}

}}

Lactacystin is an organic compound naturally synthesized by bacteria of the genus Streptomyces first identified as an inducer of neuritogenesis in neuroblastoma cells in 1991.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. The target of lactacystin was subsequently found to be the proteasome on the basis of its affinity for certain catalytic subunits of the proteasome by Fenteany and co-workers in 1995.{{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 }} 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 threonine protease. The molecule is commonly used in biochemistry and cell biology laboratories as a selective inhibitor of the proteasome.{{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 }}{{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}} The first total synthesis of lactacystin was developed in 1992 by Corey and Reichard,"Total Synthesis of Lactacystin" Corey, E. J.; Reichard, G. A. J. Am. Chem. Soc. 1992, 114, 10677. and a number of other syntheses of this molecule have also been published. There are more than 1,660 entries for lactacystin in PubMed as of January 2019.