Lactacystin
featured

    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 540261

CAS#: 133343-34-7

Description: Lactacystin is a proteasome inhibitor found in Streptomyces. It increases the Bax/Bcl-2 ratio and inhibits proliferation of glioma cells, inhibits growth and migration of smooth muscle cells, and suppresses infiltration of neutrophils and decreases levels of ICAM-1 in liver injury models.


Chemical Structure

img
Lactacystin
CAS# 133343-34-7

Theoretical Analysis

MedKoo Cat#: 540261
Name: Lactacystin
CAS#: 133343-34-7
Chemical Formula: C15H24N2O7S
Exact Mass: 376.13
Molecular Weight: 376.424
Elemental Analysis: C, 47.86; H, 6.43; N, 7.44; O, 29.75; S, 8.52

Price and Availability

Size Price Availability Quantity
1mg USD 850 2 Weeks
Bulk inquiry

Synonym: Lactacystin

IUPAC/Chemical Name: N-acetyl-S-((2S,3S,4R)-3-hydroxy-2-((S)-1-hydroxy-2-methylpropyl)-4-methyl-5-oxopyrrolidine-2-carbonyl)-L-cysteine

InChi Key: DAQAKHDKYAWHCG-AFGIITKNSA-N

InChi Code: InChI=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

SMILES Code: O=C([C@]1([C@@H](O)C(C)C)[C@@H](O)[C@@H](C)C(N1)=O)SC[C@@H](C(O)=O)NC(C)=O

Appearance: A clear film

Purity: >90% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:

Product Data:
Safety Data Sheet (SDS):
Biological target: Lactacystin, an antibiotic Streptomyces spp. metabolite, is a potent and selective proteasome inhibitor with an IC50 of 4.8 μM for 20S proteasome.
In vitro activity: Treatment of NMH cells with the proteasome inhibitor lactacystin, which prevents degradation of the NF-kappa B inhibitor proteins I kappa B, induced apoptosis. Reference: Am J Pathol. 1997 Oct;151(4):891-6. https://pubmed.ncbi.nlm.nih.gov/9327720/
In vivo activity: Six weeks of lactacystin administration to rats increased their average systolic blood pressure (SBP). In the kidneys, lactacystin reduced glomerular density, increased the glomerular tuft area, and enhanced hydroxyproline concentrations. Reference: Front Pharmacol. 2022 Sep 13;13:978337. https://pubmed.ncbi.nlm.nih.gov/36176443/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMF 20.0 53.13
DMSO 20.0 53.13
Ethanol 1.0 2.66
Water 6.9 18.28

Preparing Stock Solutions

The following data is based on the product molecular weight 376.42 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Bellas RE, FitzGerald MJ, Fausto N, Sonenshein GE. Inhibition of NF-kappa B activity induces apoptosis in murine hepatocytes. Am J Pathol. 1997 Oct;151(4):891-6. PMID: 9327720; PMCID: PMC1858057. 2. Fenteany G, Standaert RF, Lane WS, Choi S, Corey EJ, Schreiber SL. Inhibition of proteasome activities and subunit-specific amino-terminal threonine modification by lactacystin. Science. 1995 May 5;268(5211):726-31. doi: 10.1126/science.7732382. PMID: 7732382. 3. Repova K, Stanko P, Baka T, Krajcirovicova K, Aziriova S, Hrenak J, Barta A, Zorad S, Reiter RJ, Adamcova M, Simko F. Lactacystin-induced kidney fibrosis: Protection by melatonin and captopril. Front Pharmacol. 2022 Sep 13;13:978337. doi: 10.3389/fphar.2022.978337. PMID: 36176443; PMCID: PMC9513205. 4. Deneyer L, Massie A, Bentea E. Ketamine Does Not Exert Protective Properties on Dopaminergic Neurons in the Lactacystin Mouse Model of Parkinson's Disease. Front Behav Neurosci. 2018 Sep 19;12:219. doi: 10.3389/fnbeh.2018.00219. PMID: 30283309; PMCID: PMC6156534.
In vitro protocol: 1. Bellas RE, FitzGerald MJ, Fausto N, Sonenshein GE. Inhibition of NF-kappa B activity induces apoptosis in murine hepatocytes. Am J Pathol. 1997 Oct;151(4):891-6. PMID: 9327720; PMCID: PMC1858057. 2. Fenteany G, Standaert RF, Lane WS, Choi S, Corey EJ, Schreiber SL. Inhibition of proteasome activities and subunit-specific amino-terminal threonine modification by lactacystin. Science. 1995 May 5;268(5211):726-31. doi: 10.1126/science.7732382. PMID: 7732382.
In vivo protocol: 1. Repova K, Stanko P, Baka T, Krajcirovicova K, Aziriova S, Hrenak J, Barta A, Zorad S, Reiter RJ, Adamcova M, Simko F. Lactacystin-induced kidney fibrosis: Protection by melatonin and captopril. Front Pharmacol. 2022 Sep 13;13:978337. doi: 10.3389/fphar.2022.978337. PMID: 36176443; PMCID: PMC9513205. 2. Deneyer L, Massie A, Bentea E. Ketamine Does Not Exert Protective Properties on Dopaminergic Neurons in the Lactacystin Mouse Model of Parkinson's Disease. Front Behav Neurosci. 2018 Sep 19;12:219. doi: 10.3389/fnbeh.2018.00219. PMID: 30283309; PMCID: PMC6156534.

Molarity Calculator

Calculate the mass, volume, or concentration required for a solution.
=
x
x
g/mol

*When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and SDS / CoA (available online).

Reconstitution Calculator

The reconstitution calculator allows you to quickly calculate the volume of a reagent to reconstitute your vial. Simply enter the mass of reagent and the target concentration and the calculator will determine the rest.

=
÷

Dilution Calculator

Calculate the dilution required to prepare a stock solution.
x
=
x

1: Konieczny J, Czarnecka A, Kamińska K, Lenda T, Nowak P. Decreased behavioral response to intranigrally administered GABAA agonist muscimol in the lactacystin model of Parkinson's disease may result from partial lesion of nigral non-dopamine neurons: comparison to the classical neurotoxin 6-OHDA. Behav Brain Res. 2015 Apr 15;283:203-14. doi: 10.1016/j.bbr.2015.01.043. Epub 2015 Feb 2. PubMed PMID: 25655509.

2: Harrison IF, Crum WR, Vernon AC, Dexter DT. Neurorestoration induced by the HDAC inhibitor sodium valproate in the lactacystin model of Parkinson's is associated with histone acetylation and up-regulation of neurotrophic factors. Br J Pharmacol. 2015 Aug;172(16):4200-15. doi: 10.1111/bph.13208. Epub 2015 Jul 8. PubMed PMID: 26040297; PubMed Central PMCID: PMC4543623.

3: Konieczny J, Jantas D, Lenda T, Domin H, Czarnecka A, Kuter K, Śmiałowska M, Lasoń W, Lorenc-Koci E. Lack of neuroprotective effect of celastrol under conditions of proteasome inhibition by lactacystin in in vitro and in vivo studies: implications for Parkinson's disease. Neurotox Res. 2014 Oct;26(3):255-73. doi: 10.1007/s12640-014-9477-9. Epub 2014 May 20. PubMed PMID: 24842651; PubMed Central PMCID: PMC4143605.

4: Li Y, Gao H, Wang Y, Dai C. Investigation the mechanism of the apoptosis induced by lactacystin in gastric cancer cells. Tumour Biol. 2015 May;36(5):3465-70. doi: 10.1007/s13277-014-2982-x. Epub 2014 Dec 27. PubMed PMID: 25541208.

5: Konieczny J, Czarnecka A, Lenda T, Kamińska K, Lorenc-Koci E. Chronic L-DOPA treatment attenuates behavioral and biochemical deficits induced by unilateral lactacystin administration into the rat substantia nigra. Behav Brain Res. 2014 Mar 15;261:79-88. doi: 10.1016/j.bbr.2013.12.019. Epub 2013 Dec 17. PubMed PMID: 24361083.

6: Hu X, Zhang H, Zhang Y, Zhang Y, Bai L, Chen Q, Wu J, Zhang L. Differential protein profile of PC12 cells exposed to proteasomal inhibitor lactacystin. Neurosci Lett. 2014 Jul 11;575:25-30. doi: 10.1016/j.neulet.2014.05.021. Epub 2014 May 23. PubMed PMID: 24858133.

7: Konieczny J, Lenda T, Czarnecka A. Early increase in dopamine release in the ipsilateral striatum after unilateral intranigral administration of lactacystin produces spontaneous contralateral rotations in rats. Neuroscience. 2016 Jun 2;324:92-106. doi: 10.1016/j.neuroscience.2016.02.072. Epub 2016 Mar 7. PubMed PMID: 26964686.

8: Huseby NE, Ravuri C, Moens U. The proteasome inhibitor lactacystin enhances GSH synthesis capacity by increased expression of antioxidant components in an Nrf2-independent, but p38 MAPK-dependent manner in rat colorectal carcinoma cells. Free Radic Res. 2016;50(1):1-13. doi: 10.3109/10715762.2015.1100730. Epub 2015 Nov 4. PubMed PMID: 26530909.

9: Wang H, Zhang S, Zhong J, Zhang J, Luo Y, Pengfei G. The proteasome inhibitor lactacystin exerts its therapeutic effects on glioma via apoptosis: an in vitro and in vivo study. J Int Med Res. 2013 Feb;41(1):72-81. doi: 10.1177/0300060513476992. Epub 2013 Jan 24. PubMed PMID: 23569132.

10: Yoshioka S, Nagatomo M, Inoue M. Application of two direct C(sp3)-H functionalizations for total synthesis of (+)-lactacystin. Org Lett. 2015 Jan 2;17(1):90-3. doi: 10.1021/ol503291s. Epub 2014 Dec 19. PubMed PMID: 25526222.

11: Harrison IF, Anis HK, Dexter DT. Associated degeneration of ventral tegmental area dopaminergic neurons in the rat nigrostriatal lactacystin model of parkinsonism and their neuroprotection by valproate. Neurosci Lett. 2016 Feb 12;614:16-23. doi: 10.1016/j.neulet.2015.12.052. Epub 2015 Dec 29. PubMed PMID: 26742637; PubMed Central PMCID: PMC4756273.

12: Xu Y, Li D, Zeng L, Wang C, Zhang L, Wang Y, Yu Y, Liu S, Li Z. Proteasome inhibitor lactacystin enhances cisplatin cytotoxicity by increasing endoplasmic reticulum stress-associated apoptosis in HeLa cells. Mol Med Rep. 2015 Jan;11(1):189-95. doi: 10.3892/mmr.2014.2683. Epub 2014 Oct 16. PubMed PMID: 25323748; PubMed Central PMCID: PMC4237085.

13: Také A, Matsumoto A, Ōmura S, Takahashi Y. Streptomyces lactacystinicus sp. nov. and Streptomyces cyslabdanicus sp. nov., producing lactacystin and cyslabdan, respectively. J Antibiot (Tokyo). 2015 May;68(5):322-7. doi: 10.1038/ja.2014.162. Epub 2014 Dec 10. Erratum in: J Antibiot (Tokyo). 2015 Nov;68(11):719. PubMed PMID: 25491896.

14: Ito Y, Fukushima H, Katagiri T, Seo Y, Hirata S, Zhang M, Hosokawa R, Jimi E. Lactacystin, a proteasome inhibitor, enhances BMP-induced osteoblastic differentiation by increasing active Smads. Biochem Biophys Res Commun. 2011 Apr 1;407(1):225-9. doi: 10.1016/j.bbrc.2011.03.003. Epub 2011 Mar 4. PubMed PMID: 21377449.

15: Dai MF, Hu D, Zhao D. [Effect of epigallocatechin gallate on lactacystin-induced PC12 cell injury]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2011 May;31(5):672-5. Chinese. PubMed PMID: 21812272.

16: Xia Y, Chen BY, Sun XL, Duan L, Gao GD, Wang JJ, Yung KK, Chen LW. Presence of proNGF-sortilin signaling complex in nigral dopamine neurons and its variation in relation to aging, lactacystin and 6-OHDA insults. Int J Mol Sci. 2013 Jul 8;14(7):14085-104. doi: 10.3390/ijms140714085. PubMed PMID: 23880857; PubMed Central PMCID: PMC3742233.

17: Fenteany G, Standaert RF, Lane WS, Choi S, Corey EJ, Schreiber SL. Inhibition of proteasome activities and subunit-specific amino-terminal threonine modification by lactacystin. Science. 1995 May 5;268(5211):726-31. PubMed PMID: 7732382.

18: Lorenc-Koci E, Lenda T, Antkiewicz-Michaluk L, Wardas J, Domin H, Smiałowska M, Konieczny J. Different effects of intranigral and intrastriatal administration of the proteasome inhibitor lactacystin on typical neurochemical and histological markers of Parkinson's disease in rats. Neurochem Int. 2011 Jun;58(7):839-49. doi: 10.1016/j.neuint.2011.03.013. Epub 2011 Mar 16. PubMed PMID: 21419185.

19: Rockwell CE, Qureshi N. Differential effects of lactacystin on cytokine production in activated Jurkat cells and murine splenocytes. Cytokine. 2010 Jul;51(1):12-7. doi: 10.1016/j.cyto.2010.03.018. Epub 2010 Apr 27. PubMed PMID: 20427199; PubMed Central PMCID: PMC2911229.

20: Dick LR, Cruikshank AA, Grenier L, Melandri FD, Nunes SL, Stein RL. Mechanistic studies on the inactivation of the proteasome by lactacystin: a central role for clasto-lactacystin beta-lactone. J Biol Chem. 1996 Mar 29;271(13):7273-6. PubMed PMID: 8631740.