Page last updated: 2024-11-08

leupeptins

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Description

Leupeptins: A group of acylated oligopeptides produced by Actinomycetes that function as protease inhibitors. They have been known to inhibit to varying degrees trypsin, plasmin, KALLIKREINS, papain and the cathepsins. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID425562
SCHEMBL ID25361
MeSH IDM0012428

Synonyms (5)

Synonym
nsc175152
leupeptins
nsc-175152
SCHEMBL25361
BMGMINKVTPDDRZ-UHFFFAOYSA-N

Research Excerpts

Toxicity

ExcerptReferenceRelevance
" Intriguingly, Abeta40 plus leupeptin induced intracellular accumulation of the more toxic Abeta, Abeta42, in a small group of septal neurons."( Protease inhibitor coinfusion with amyloid beta-protein results in enhanced deposition and toxicity in rat brain.
Cole, GM; Frautschy, SA; Harris-White, ME; Horn, DL; Mendoza, JJ; Saido, TC; Sigel, JJ; Yang, F, 1998
)
0.3
" Leupeptin, an inhibitor acting on a broad spectrum of cellular serine proteases, was less toxic but resulted in definite morphological alteration of the cells."( Differential toxicity of protease inhibitors in cultures of cerebellar granule neurons.
Contestabile, A; Monti, B; Sparapani, M, 1998
)
0.3
" HepG2 cells over-expressing CYP2E1 (E47 cells) were treated with arachidonic acid (AA) plus iron, agents important in development of alcoholic liver injury and which are toxic to E47 cells by a mechanism dependent on CYP2E1, oxidative stress, and lipid peroxidation."( Proteasome inhibition potentiates CYP2E1-mediated toxicity in HepG2 cells.
Cederbaum, AI; Pérez, MJ, 2003
)
0.32
" Recent evidence suggests a cytosolic fraction of PrP (cyPrP) functions either as an initiating factor or toxic element of prion disease."( Cytosolic prion protein toxicity is independent of cellular prion protein expression and prion propagation.
Ciaccio, MF; Mastrianni, JA; Norstrom, EM; Rassbach, B; Wollmann, R, 2007
)
0.34
" Efforts to purify the toxic activity revealed that it is a highly stable, lipophilic, and chemically unique small molecule."( Investigating bacterial sources of toxicity as an environmental contributor to dopaminergic neurodegeneration.
Armagost, J; Blalock, JE; Caldwell, GA; Caldwell, KA; Chen, J; DeLeon, SM; Findlay, RH; Hodges, TW; Memon, SB; Olson, JB; Ruan, Q; Standaert, DG; Tucci, ML; Webber, PJ, 2009
)
0.35
" Proteases activation is responsible for triggering deadly cascades during cell damage in toxic models."( Time-course correlation of early toxic events in three models of striatal damage: modulation by proteases inhibition.
Ali, SF; Carrillo-Mora, P; Chánez-Cárdenas, ME; Elinos-Calderón, D; Konigsberg, M; Morán, J; Pérez-De La Cruz, G; Pérez-De La Cruz, V; Santamaría, A; Silva-Adaya, D,
)
0.13
" Using siRNA technology, we show here that MCPIP1 expression contributes to the toxic properties of MG-132 in HeLa cells."( MCPIP1 contributes to the toxicity of proteasome inhibitor MG-132 in HeLa cells by the inhibition of NF-κB.
Dziendziel, M; Jura, J; Skalniak, L, 2014
)
0.4
" However, ALLN is toxic to retinal neurons to some extent."( The Toxic Effect of ALLN on Primary Rat Retinal Neurons.
Chen, D; Huang, JF; Li, N; Liao, LS; Shang, L; Wang, SC; Xiong, K, 2016
)
0.43
" However, the novel strategy is required to reduce life-threatening adverse effects of PNT including ischemic cardiovascular disease."( Involvement of MCL1, c-myc, and cyclin D2 protein degradation in ponatinib-induced cytotoxicity against T315I(+) Ph+leukemia cells.
Abe, A; Hayakawa, F; Ichihara, M; Inoue, C; Kawamoto, Y; Murate, T; Nishizawa, Y; Nozawa, Y; Sobue, S; Suzuki, M, 2020
)
0.56

Compound-Compound Interactions

ExcerptReferenceRelevance
" We investigated the effects of the proteasome inhibitors MG115 and PSI alone or in combination with different concentrations of the antiandrogen hydroxyflutamide on the cellular proliferation, apoptosis and viability of 10 prostatic adenocarcinoma cell cultures."( Proteasome inhibitors and their combination with antiandrogens: effects on apoptosis, cellular proliferation and viability of prostatic adenocarcinoma cell cultures.
Stöckle, M; Tahmatzopoulos, A; Unteregger, G; Wullich, B; Zwergel, T; Zwergel, U, 2004
)
0.32
" A strong synergistic apoptosis-inducing effect of the combination of rhTRAIL and MG132, especially in CIN II/III lesions indicates that rhTRAIL combined with proteasome inhibitors deserves exploration as medical treatment for CIN II/III."( A robust ex vivo model for evaluation of induction of apoptosis by rhTRAIL in combination with proteasome inhibitor MG132 in human premalignant cervical explants.
de Jong, S; de Vries, EG; Hollema, H; Hougardy, BM; Reesink-Peters, N; ten Hoor, KA; van den Heuvel, FA; van der Zee, AG, 2008
)
0.35

Bioavailability

ExcerptReferenceRelevance
" It is produced as a latent complex and the main limiting step in TGFbeta bioavailability is its activation."( Tryptase activates TGFbeta in human airway smooth muscle cells via direct proteolysis.
Jenkins, G; Knox, A; Pang, L; Porte, J; Tatler, AL, 2008
)
0.35
" Our aim in this study was to investigate the anti-inflammatory effects, absorption, and bioavailability of Artepillin C in mice."( Anti-inflammatory effects of a bioavailable compound, Artepillin C, in Brazilian propolis.
Abreu, SR; Bretz, WA; Dirsch, VM; Hori, H; Koyama, D; Nagasawa, H; Paulino, N; Scremin, A; Uto, Y; Vollmar, AM, 2008
)
0.35
"One of the main functions of A Disintegrin and Metalloproteinase 10 (ADAM10) is to regulate the bioavailability of adhesion molecules and ligands to various cellular-signaling receptors."( Constitutive activation of metalloproteinase ADAM10 in mantle cell lymphoma promotes cell growth and activates the TNFα/NFκB pathway.
Anand, M; Armanious, H; Belch, A; Gelebart, P; Lai, R, 2011
)
0.37
" These findings have provided the impetus to develop second generation, orally bioavailable SERDs with which quantitative turnover of ERα in tumors can be achieved."( The turnover of estrogen receptor α by the selective estrogen receptor degrader (SERD) fulvestrant is a saturable process that is not required for antagonist efficacy.
Marks, JR; McDonnell, DP; Wardell, SE, 2011
)
0.37

Dosage Studied

ExcerptRelevanceReference
" Dose-response studies showed, however, that the State 2 pathway was more sensitive to leupeptin or monensin than the State 1 pathway."( Differential effects of leupeptin, monensin and colchicine on ligand degradation mediated by the two asialoglycoprotein receptor pathways in isolated rat hepatocytes.
Clarke, BL; Weigel, PH, 1989
)
0.28
" This method is simple and sensitive enough to permit the quantification of leupeptin in biological samples from mice dosed with leupeptin."( High-performance liquid chromatographic method for monitoring leupeptin in mouse serum and muscle by pre-column fluorescence derivatization with benzoin.
Ishida, J; Kai, M; Miura, T; Ohkura, Y, 1985
)
0.27
" Kinetic dose-response studies showed that the number of cells induced to release virus was dependent on TPA concentration and the time of assay following TPA exposure."( Induction of type-C retrovirus by the tumor promotor TPA.
Hellman, A; Hellman, KB, 1981
)
0.26
" At the low dosage used, leupeptin had no effect on the repair process of skeletal muscle after exercise injuries, although several proteolytic processes occur during the regeneration."( Effects of the protease inhibitor leupeptin on proteolytic activities and regeneration of mouse skeletal muscles after exercise injuries.
Salminen, A, 1984
)
0.27
" Results of a controlled, dose-response study indicated that leupeptin was absorbed into plasma by the oral route of administration."( Neuromuscular recovery after peripheral nerve repair: effects of an orally-administered peptide in a primate model.
Badalamente, MA; Hurst, LC; Stracher, A, 1995
)
0.29
" Dose-response and time course studies of the effects of heat shock and anisomycin treatment showed a close correlation of the activation of JNK and hyperphosphorylation of HSF1."( JNK phosphorylates the HSF1 transcriptional activation domain: role of JNK in the regulation of the heat shock response.
Liu, AY; Park, J, 2001
)
0.31
" Thus, ligand-independent translocation of the AHR to the nucleus was not sufficient to induce CYP1A1 in the absence of ligand, but reductions in the level of the endogenous AHR protein pool shifted the dose-response curve for TCDD to the right."( Ligand-dependent and independent modulation of aryl hydrocarbon receptor localization, degradation, and gene regulation.
Pollenz, RS; Song, Z, 2002
)
0.31
"" While investigators continue to examine the best dosing paradigms for gentamicin in the treatment of Ménière's disease and for steroids in the treatment of hearing loss, they have also begun to focus on the use of other agents."( Sustained-release delivery of leupeptin in the chinchilla: hearing results.
Balough, BJ; Finley, JC; Gottshall, KR; Hoffer, ME; Killian, P; Shulman, A; Wester, D, 2003
)
0.32
" Dose-response experiments indicate that 1CT+7 cells are fourfold preferentially sensitive to AICAR compared to diploid cells."( Aneuploid human colonic epithelial cells are sensitive to AICAR-induced growth inhibition through EGFR degradation.
Kaisani, AA; Kim, SB; Ly, P; Marian, G; Shay, JW; Wright, WE, 2013
)
0.39
" Conversely, the MG132 dose-response curve was unaffected by co-administration of EGCG."( EGCG antagonizes Bortezomib cytotoxicity in prostate cancer cells by an autophagic mechanism.
Bettuzzi, S; Bonacini, M; Giovanna Troglio, M; Modernelli, A; Naponelli, V; Ramazzina, I; Rizzi, F, 2015
)
0.42
" While repeated dosing with the milder 75 mg/kg dose did not cause mitochondrial protein adduct formation, JNK activation, or liver injury, autophagy inhibition resulted in hepatocyte death even at this lower dose."( Impaired protein adduct removal following repeat administration of subtoxic doses of acetaminophen enhances liver injury in fed mice.
Akakpo, JY; Ding, WX; Jaeschke, H; Nguyen, NT; Ramachandran, A; Weemhoff, JL, 2021
)
0.62
" Half dosage of UPS genes reduces OPMD muscle defects suggesting a pathological increase of UPS activity in the disease."( Activation of the ubiquitin-proteasome system contributes to oculopharyngeal muscular dystrophy through muscle atrophy.
Al Hayek, S; Barbezier, N; Chartier, A; Coux, O; Naït-Saïdi, R; Ribot, C; Simonelig, M; Soler, C, 2022
)
0.72
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (3,827)

TimeframeStudies, This Drug (%)All Drugs %
pre-1990565 (14.76)18.7374
1990's604 (15.78)18.2507
2000's1376 (35.96)29.6817
2010's1164 (30.42)24.3611
2020's118 (3.08)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 6.39

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be weak demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index6.39 (24.57)
Research Supply Index8.27 (2.92)
Research Growth Index4.66 (4.65)
Search Engine Demand Index0.00 (26.88)
Search Engine Supply Index0.00 (0.95)

This Compound (6.39)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials4 (0.10%)5.53%
Reviews29 (0.75%)6.00%
Case Studies5 (0.13%)4.05%
Observational0 (0.00%)0.25%
Other3,853 (99.02%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]