Page last updated: 2024-12-07

peptide elongation factor 2

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

Description

(S)-thalidomide : A 2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione that has S-configuration at the chiral centre. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Peptide Elongation Factor 2: Peptide Elongation Factor 2 catalyzes the translocation of peptidyl-tRNA from the A site to the P site of eukaryotic ribosomes by a process linked to the hydrolysis of GTP to GDP. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID92142
CHEMBL ID426123
CHEBI ID61918
SCHEMBL ID455269
MeSH IDM0328223
PubMed CID148754
MeSH IDM0328223

Synonyms (59)

Synonym
NCGC00024708-01
NCGC00016220-01
NCGC00015989-01
tocris-0652
lopac-t-144
l-thalidomide
841-67-8
(-)-thalidomide
nsc 91730
phthalimide, n-(2,6-dioxo-3-piperidyl)-, (-)-
1h-isoindole-1,3(2h)-dione, 2-(2,6-dioxo-3-piperidinyl)-, (s)-
thalidomide, l-
phthalimide, n-(2,6-dioxo-3-piperidyl)-, l-(-)-
s-(-)-thalidomide
smr000857221
MLS001333074
MLS001333073
(-)-thalidomide, >98%, solid
(s)-thalidomide
CHEMBL426123
chebi:61918 ,
2-[(3s)-2,6-dioxopiperidin-3-yl]isoindole-1,3-dione
2-[(3s)-2,6-dioxopiperidin-3-yl]-1h-isoindole-1,3(2h)-dione
(s)-(-)-thalidomide
2-[(3s)-2,6-dioxo-3-piperidinyl]isoindole-1,3-dione
2-[(3s)-2,6-bis(oxidanylidene)piperidin-3-yl]isoindole-1,3-dione
A828082
unii-tg87fsr590
thalidomide, (-)-
tg87fsr590 ,
HMS2230K15
NCGC00015989-02
SCHEMBL455269
s-thalidomide
EF2 ,
thalidomide, (s)-
enmd-0995
s(-)-3-(3-amino-phthalimido)-glutaramide
DTXSID1046972
4CI1
(s)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione
bdbm65457
Q27131493
HY-14658A
CS-0021928
thalidomide; n-(2,6-dioxo-3-piperidyl)phalimide
MS-23635
EN300-7507076
2-[(3s)-2,6-dioxopiperidin-3-yl]-2,3-dihydro-1h-isoindole-1,3-dione
AKOS040736375
EX-A7843G
4,7-methano-1h-indene-1,3(2h)-dione, 3a,7a-dichloro-2-(dichloromethylene)-3a,4,7,7a-tetrahydro-
2-dichloromethylene-3a,7a-dichloro-3a,4,7,7a-tetrahydro-4,7-methanoindene-1,3-dione
ef 2
55739-78-1
peptide elongation factor 2
3a,7a-dichloro-2-(dichloromethylidene)-3a,4,7,7a-tetrahydro-1h-4,7-methanoindene-1,3(2h)-dione
DTXSID90971114
2,6-dichloro-4-(dichloromethylidene)tricyclo[5.2.1.02,6]dec-8-ene-3,5-dione

Research Excerpts

Toxicity

ExcerptReferenceRelevance
" In our experiment, a cell viability assay revealed a strong and time-dependent toxic effect of oligomeric Aβ1-42 which was supported by dramatic morphological changes."( Proteomic study of the toxic effect of oligomeric Aβ1-42 in situ prepared from 'iso-Aβ1-42'.
Bozsó, Z; Datki, ZL; Földi, I; Janáky, T; Penke, B; Szabó, Z, 2011
)
0.37
" Safety and tolerability (primary outcome of the single ascending dose study and secondary outcome of the volunteer infection study) were assessed by frequency and severity of adverse events."( Safety, pharmacokinetics, and antimalarial activity of the novel plasmodium eukaryotic translation elongation factor 2 inhibitor M5717: a first-in-human, randomised, placebo-controlled, double-blind, single ascending dose study and volunteer infection stu
Bagchus, WM; Bezuidenhout, D; Dhingra, SK; Fidock, DA; Giddins, MJ; Khandelwal, A; Marquart, L; McCarthy, JS; Odedra, A; Oeuvray, C; Tappert, A; Webb, L; Webster, R; Yalkinoglu, Ö; Yin, X, 2021
)
0.62
" No adverse event was serious; all M5717-related adverse events were mild or moderate in severity and transient, with increased frequency observed at doses above 1250 mg."( Safety, pharmacokinetics, and antimalarial activity of the novel plasmodium eukaryotic translation elongation factor 2 inhibitor M5717: a first-in-human, randomised, placebo-controlled, double-blind, single ascending dose study and volunteer infection stu
Bagchus, WM; Bezuidenhout, D; Dhingra, SK; Fidock, DA; Giddins, MJ; Khandelwal, A; Marquart, L; McCarthy, JS; Odedra, A; Oeuvray, C; Tappert, A; Webb, L; Webster, R; Yalkinoglu, Ö; Yin, X, 2021
)
0.62

Pharmacokinetics

ExcerptReferenceRelevance
" The pharmacokinetic profile of M5717 was also characterised (primary outcome of the volunteer infection study and secondary outcome of the single ascending dose study)."( Safety, pharmacokinetics, and antimalarial activity of the novel plasmodium eukaryotic translation elongation factor 2 inhibitor M5717: a first-in-human, randomised, placebo-controlled, double-blind, single ascending dose study and volunteer infection stu
Bagchus, WM; Bezuidenhout, D; Dhingra, SK; Fidock, DA; Giddins, MJ; Khandelwal, A; Marquart, L; McCarthy, JS; Odedra, A; Oeuvray, C; Tappert, A; Webb, L; Webster, R; Yalkinoglu, Ö; Yin, X, 2021
)
0.62
" Maximum blood concentrations occurred 1-7 h after dosing, and a long half-life was observed (146-193 h at doses ≥200 mg)."( Safety, pharmacokinetics, and antimalarial activity of the novel plasmodium eukaryotic translation elongation factor 2 inhibitor M5717: a first-in-human, randomised, placebo-controlled, double-blind, single ascending dose study and volunteer infection stu
Bagchus, WM; Bezuidenhout, D; Dhingra, SK; Fidock, DA; Giddins, MJ; Khandelwal, A; Marquart, L; McCarthy, JS; Odedra, A; Oeuvray, C; Tappert, A; Webb, L; Webster, R; Yalkinoglu, Ö; Yin, X, 2021
)
0.62

Compound-Compound Interactions

ExcerptReferenceRelevance
" We used 2-D difference gel electrophoresis combined with the fluorescence staining Pro-Q Diamond selective for phosphorylated proteins to monitor changes in the phosphorylation status of possible substrates."( 2-D Difference in gel electrophoresis combined with Pro-Q Diamond staining: a successful approach for the identification of kinase/phosphatase targets.
Caterino, M; Forte, E; Orsatti, L; Pessi, A; Talamo, F; Tomei, L, 2009
)
0.35
" donovani was assessed in native condition, herein we generated recombinant HSP70 and tested its potential to stimulate immune responses in lymphocytes of cured Leishmania infected hamsters as well as in the peripheral blood mononuclear cells (PBMCs) of cured patients of VL either individually or in combination with above mentioned recombinant proteins."( Th1 stimulatory proteins of Leishmania donovani: comparative cellular and protective responses of rTriose phosphate isomerase, rProtein disulfide isomerase and rElongation factor-2 in combination with rHSP70 against visceral leishmaniasis.
Dube, A; Jaiswal, AK; Joshi, S; Khare, P; Kushawaha, PK; Sundar, S, 2014
)
0.4

Dosage Studied

ExcerptRelevanceReference
" When the amount of EF-2 exceeded that of ribosomes sordarin inhibited the GTPase activity following an inverted bell-shaped dose-response curve, whereas when EF-2 and ribosomes were in equimolar concentrations sordarin yielded a typical sigmoidal dose-dependent inhibition."( Sordarin inhibits fungal protein synthesis by blocking translocation differently to fusidic acid.
Domínguez, JM; Gómez-Lorenzo, MG; Martín, JJ, 1999
)
0.3
" Dose-response curves in myometrial cells expressing the endogenous OTR indicated a significant effect of OT on eukaryotic elongation factor 2 dephosphorylation at 1 nM, a concentration close to the dissociation constant (K(d)) of OT."( Oxytocin induces dephosphorylation of eukaryotic elongation factor 2 in human myometrial cells.
Carrier, ME; Devost, D; Girotti, M; Russo, C; Zingg, HH, 2005
)
0.33
" A sentinel dosing strategy was used for each dose cohort whereby two participants (one assigned to M5717 and one assigned to placebo) were initially randomised and dosed."( Safety, pharmacokinetics, and antimalarial activity of the novel plasmodium eukaryotic translation elongation factor 2 inhibitor M5717: a first-in-human, randomised, placebo-controlled, double-blind, single ascending dose study and volunteer infection stu
Bagchus, WM; Bezuidenhout, D; Dhingra, SK; Fidock, DA; Giddins, MJ; Khandelwal, A; Marquart, L; McCarthy, JS; Odedra, A; Oeuvray, C; Tappert, A; Webb, L; Webster, R; Yalkinoglu, Ö; Yin, X, 2021
)
0.62
" Transient oral hypoesthesia (in three participants) and blurred vision (in four participants) were observed in the 1800 mg or 2100 mg groups and constituted an unknown risk; thus, further dosing was suspended after dosing of the two sentinel individuals in the 2100 mg cohort."( Safety, pharmacokinetics, and antimalarial activity of the novel plasmodium eukaryotic translation elongation factor 2 inhibitor M5717: a first-in-human, randomised, placebo-controlled, double-blind, single ascending dose study and volunteer infection stu
Bagchus, WM; Bezuidenhout, D; Dhingra, SK; Fidock, DA; Giddins, MJ; Khandelwal, A; Marquart, L; McCarthy, JS; Odedra, A; Oeuvray, C; Tappert, A; Webb, L; Webster, R; Yalkinoglu, Ö; Yin, X, 2021
)
0.62
" Simulated pharmacokinetic/toxicokinetic profiles were used to design the dosing schedule for preclinical safety studies and to determine the 14-day total exposure."( An innovative study design with intermittent dosing to generate a GLP-regulatory package in preclinical species for long lasting molecule M5717, inhibitor of Plasmodium eukaryotic translation elongation factor 2.
Abla, N; Bagchus, W; Bebrevska, L; Hewitt, P; Lignet, F; Oeuvray, C, 2022
)
0.72
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (1)

RoleDescription
teratogenic agentA role played by a chemical compound in biological systems with adverse consequences in embryo developments, leading to birth defects, embryo death or altered development, growth retardation and functional defect.
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Drug Classes (1)

ClassDescription
2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dioneA dicarboximide that is isoindole-1,3(2H)-dione in which the hydrogen attached to the nitrogen is substituted by a 2,6-dioxopiperidin-3-yl group.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Protein Targets (5)

Potency Measurements

ProteinTaxonomyMeasurementAverage (µ)Min (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Chain A, TYROSYL-DNA PHOSPHODIESTERASEHomo sapiens (human)Potency15.84890.004023.8416100.0000AID485290
Chain A, Beta-lactamaseEscherichia coli K-12Potency0.35480.044717.8581100.0000AID485294
thyroid stimulating hormone receptorHomo sapiens (human)Potency3.98110.001318.074339.8107AID926; AID938
gemininHomo sapiens (human)Potency4.29880.004611.374133.4983AID624296; AID624297
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Protein cereblonHomo sapiens (human)IC50 (µMol)10.00000.28601.70663.0000AID1794853
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (7)

Processvia Protein(s)Taxonomy
protein ubiquitinationProtein cereblonHomo sapiens (human)
positive regulation of Wnt signaling pathwayProtein cereblonHomo sapiens (human)
negative regulation of protein-containing complex assemblyProtein cereblonHomo sapiens (human)
positive regulation of protein-containing complex assemblyProtein cereblonHomo sapiens (human)
negative regulation of monoatomic ion transmembrane transportProtein cereblonHomo sapiens (human)
locomotory exploration behaviorProtein cereblonHomo sapiens (human)
proteasome-mediated ubiquitin-dependent protein catabolic processProtein cereblonHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (3)

Processvia Protein(s)Taxonomy
protein bindingProtein cereblonHomo sapiens (human)
transmembrane transporter bindingProtein cereblonHomo sapiens (human)
metal ion bindingProtein cereblonHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (6)

Processvia Protein(s)Taxonomy
nucleusProtein cereblonHomo sapiens (human)
cytoplasmProtein cereblonHomo sapiens (human)
cytosolProtein cereblonHomo sapiens (human)
membraneProtein cereblonHomo sapiens (human)
perinuclear region of cytoplasmProtein cereblonHomo sapiens (human)
Cul4A-RING E3 ubiquitin ligase complexProtein cereblonHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (28)

Assay IDTitleYearJournalArticle
AID588497High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, MLPCN compound set2010Current protocols in cytometry, Oct, Volume: Chapter 13Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening.
AID588497High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, MLPCN compound set2006Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5
Microsphere-based protease assays and screening application for lethal factor and factor Xa.
AID588497High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, MLPCN compound set2010Assay and drug development technologies, Feb, Volume: 8, Issue:1
High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors.
AID588501High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, MLPCN compound set2010Current protocols in cytometry, Oct, Volume: Chapter 13Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening.
AID588501High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, MLPCN compound set2006Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5
Microsphere-based protease assays and screening application for lethal factor and factor Xa.
AID588501High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, MLPCN compound set2010Assay and drug development technologies, Feb, Volume: 8, Issue:1
High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors.
AID504812Inverse Agonists of the Thyroid Stimulating Hormone Receptor: HTS campaign2010Endocrinology, Jul, Volume: 151, Issue:7
A small molecule inverse agonist for the human thyroid-stimulating hormone receptor.
AID588499High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, MLPCN compound set2010Current protocols in cytometry, Oct, Volume: Chapter 13Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening.
AID588499High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, MLPCN compound set2006Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5
Microsphere-based protease assays and screening application for lethal factor and factor Xa.
AID588499High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, MLPCN compound set2010Assay and drug development technologies, Feb, Volume: 8, Issue:1
High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors.
AID504810Antagonists of the Thyroid Stimulating Hormone Receptor: HTS campaign2010Endocrinology, Jul, Volume: 151, Issue:7
A small molecule inverse agonist for the human thyroid-stimulating hormone receptor.
AID651635Viability Counterscreen for Primary qHTS for Inhibitors of ATXN expression
AID1745845Primary qHTS for Inhibitors of ATXN expression
AID423811Cytotoxicity against human IM9 cells assessed as cell viability at 100 ug/ml after 72 hrs by MTT assay2009Bioorganic & medicinal chemistry letters, Jul-15, Volume: 19, Issue:14
Synthesis, configurational stability and stereochemical biological evaluations of (S)- and (R)-5-hydroxythalidomides.
AID604734Antiangiogenesis activity against fertilized chicken egg chorioallantoic membrane assessed as inhibition of neovascularization at 2.5 nmol/egg by CAM vessel development assay relative to control2010Bioorganic & medicinal chemistry letters, Nov-15, Volume: 20, Issue:22
Concise synthesis and antiangiogenic activity of artemisinin-glycolipid hybrids on chorioallantoic membranes.
AID423809Cytotoxicity against human KB cells assessed as cell viability at 100 ug/ml after 72 hrs by MTT assay2009Bioorganic & medicinal chemistry letters, Jul-15, Volume: 19, Issue:14
Synthesis, configurational stability and stereochemical biological evaluations of (S)- and (R)-5-hydroxythalidomides.
AID423805Antiangiogenic activity against VEGF-induced HUVEC assessed as tube area at 100 uM after 11 days by BCIP/NBT visualization assay2009Bioorganic & medicinal chemistry letters, Jul-15, Volume: 19, Issue:14
Synthesis, configurational stability and stereochemical biological evaluations of (S)- and (R)-5-hydroxythalidomides.
AID604733Embryotoxicity in fertilized chicken embryo at 2.5 nmol/egg2010Bioorganic & medicinal chemistry letters, Nov-15, Volume: 20, Issue:22
Concise synthesis and antiangiogenic activity of artemisinin-glycolipid hybrids on chorioallantoic membranes.
AID262123Antiangiogenic activity at chorioallantoic membrane of chick embryo at 5 nmol per egg2006Bioorganic & medicinal chemistry letters, Mar-01, Volume: 16, Issue:5
Antiangiogenic activity of deoxoartemisinin derivatives on chorioallantoic membrane.
AID423804Stability assessed as half life at pH 8.782009Bioorganic & medicinal chemistry letters, Jul-15, Volume: 19, Issue:14
Synthesis, configurational stability and stereochemical biological evaluations of (S)- and (R)-5-hydroxythalidomides.
AID423810Cytotoxicity against human MCF7 cells assessed as cell viability at 100 ug/ml after 72 hrs by MTT assay2009Bioorganic & medicinal chemistry letters, Jul-15, Volume: 19, Issue:14
Synthesis, configurational stability and stereochemical biological evaluations of (S)- and (R)-5-hydroxythalidomides.
AID423812Cytotoxicity against human HS-Sultan cells assessed as cell viability at 100 ug/ml after 72 hrs by MTT assay2009Bioorganic & medicinal chemistry letters, Jul-15, Volume: 19, Issue:14
Synthesis, configurational stability and stereochemical biological evaluations of (S)- and (R)-5-hydroxythalidomides.
AID423803Stability assessed as half life at pH 7.232009Bioorganic & medicinal chemistry letters, Jul-15, Volume: 19, Issue:14
Synthesis, configurational stability and stereochemical biological evaluations of (S)- and (R)-5-hydroxythalidomides.
AID423802Stability assessed as half life at pH 6.242009Bioorganic & medicinal chemistry letters, Jul-15, Volume: 19, Issue:14
Synthesis, configurational stability and stereochemical biological evaluations of (S)- and (R)-5-hydroxythalidomides.
AID1508630Primary qHTS for small molecule stabilizers of the endoplasmic reticulum resident proteome: Secreted ER Calcium Modulated Protein (SERCaMP) assay2021Cell reports, 04-27, Volume: 35, Issue:4
A target-agnostic screen identifies approved drugs to stabilize the endoplasmic reticulum-resident proteome.
AID1347154Primary screen GU AMC qHTS for Zika virus inhibitors2020Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49
Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID977611Experimentally measured binding affinity data (Kd) for protein-ligand complexes derived from PDB2014Nature, Aug-07, Volume: 512, Issue:7512
Structure of the DDB1-CRBN E3 ubiquitin ligase in complex with thalidomide.
AID1794853Thalidomide analog bead assay from Article 10.1038/leu.2012.119: \\Cereblon is a direct protein target for immunomodulatory and antiproliferative activities of lenalidomide and pomalidomide.\\2012Leukemia, Nov, Volume: 26, Issue:11
Cereblon is a direct protein target for immunomodulatory and antiproliferative activities of lenalidomide and pomalidomide.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (780)

TimeframeStudies, This Drug (%)All Drugs %
pre-1990134 (17.18)18.7374
1990's197 (25.26)18.2507
2000's221 (28.33)29.6817
2010's169 (21.67)24.3611
2020's59 (7.56)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 11.91

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 Index11.91 (24.57)
Research Supply Index2.56 (2.92)
Research Growth Index4.48 (4.65)
Search Engine Demand Index0.00 (26.88)
Search Engine Supply Index0.00 (0.95)

This Compound (11.91)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials0 (0.00%)5.53%
Trials8 (1.01%)5.53%
Reviews0 (0.00%)6.00%
Reviews51 (6.46%)6.00%
Case Studies0 (0.00%)4.05%
Case Studies1 (0.13%)4.05%
Observational0 (0.00%)0.25%
Observational0 (0.00%)0.25%
Other12 (100.00%)84.16%
Other730 (92.41%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]