Page last updated: 2024-12-11

sdz eaa 494

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

Description

midafotel : A member of the class of piperazines that is piperazine substituted by a carboxy group at position 2R and a (1E)-1-phosphonoprop-1-en-3-yl group at position 4. It is an antagonist of N-methyl-D-aspartate receptors (NMDARs) and was in clinical development by Novartis for the treatment of cognition disorders and brain injuries (now discontinued). [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]

Cross-References

ID SourceID
PubMed CID6435801
CHEMBL ID90564
CHEBI ID180900
SCHEMBL ID1061150
SCHEMBL ID1061155
MeSH IDM0179557

Synonyms (42)

Synonym
CHEMBL90564
(2r)-4-[(2e)-3-phosphono-2-propenyl]-2-piperazinecarboxylic acid
(r)-4-[(e)-3-phosphonoprop-2-enyl]piperazine-2-carboxylic acid
d-cppene
midafotelum
(r)-cpp-ene
(2r)-4-[(2e)-3-phosphonoprop-2-en-1-yl]piperazine-2-carboxylic acid
d-4-[(2e)-3-phosphono-2-propenyl]-2-piperazinecarboxylic acid
CHEBI:180900
d(-)cppene
sdz-eaa-494
117414-74-1
NCGC00092278-01
(-)-(r)-4-((e)-3-phosphonoallyl)-2-piperazinecarboxylic acid
d-cpp-ene
midafotel
sdz-eaa 494
c8h15n2o5p
NCGC00092278-02
(2r)-4-[(e)-3-phosphonoprop-2-enyl]piperazine-2-carboxylic acid
unii-7lyu6zf84g
midafotel [inn]
7lyu6zf84g ,
cas-117414-74-1
tox21_111189
dtxcid9025740
dtxsid1045740 ,
midafotel [who-dd]
4-(3-phosphono-2-propenyl)-2-piperazinecarboxylic acid, (r-(e))
(r)-4-((e)-3-phosphonoprop-2-enyl)piperazine-2-carboxylic acid
SCHEMBL1061150
SCHEMBL1061155
AKOS024456500
2-piperazinecarboxylicacid,4-[(2e)-3-phosphono-2-propenyl]-,(2r)-
(r,e)-4-(3-phosphonoallyl)piperazine-2-carboxylic acid
(r)-4-((e)-3-phosphonoallyl)-2-piperazinecarboxylic acid
d-4-[(2e)-3-phosphono-2-propenyl]-2-piperazinecarboxylic acid;midafotel, sdz eaa 494
(r)-cppene (sdz eaa 494)
HB0023
(r,e)-4-(3-phosphonoallyl)piperazine-2-carboxylicacid
CS-0029299
HY-107718

Research Excerpts

Bioavailability

ExcerptReferenceRelevance
"The ATP-binding cassette transporter P-glycoprotein (P-gp) is known to limit both brain penetration and oral bioavailability of many chemotherapy drugs."( A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
Ambudkar, SV; Brimacombe, KR; Chen, L; Gottesman, MM; Guha, R; Hall, MD; Klumpp-Thomas, C; Lee, OW; Lee, TD; Lusvarghi, S; Robey, RW; Shen, M; Tebase, BG, 2019
)
0.51
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (3)

RoleDescription
NMDA receptor antagonistAny substance that inhibits the action of N-methyl-D-aspartate (NMDA) receptors. They tend to induce a state known as dissociative anesthesia, marked by catalepsy, amnesia, and analgesia, while side effects can include hallucinations, nightmares, and confusion. Due to their psychotomimetic effects, many NMDA receptor antagonists are used as recreational drugs.
neuroprotective agentAny compound that can be used for the treatment of neurodegenerative disorders.
anticonvulsantA drug used to prevent seizures or reduce their severity.
[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 (5)

ClassDescription
piperazinecarboxylic acid
monocarboxylic acidAn oxoacid containing a single carboxy group.
phosphonic acidsHP(=O)(OH)2 (phosphonic acid) and its P-substituted derivatives.
olefinic compoundAny organic molecular entity that contains at least one C=C bond.
tertiary amino compoundA compound formally derived from ammonia by replacing three hydrogen atoms by organyl groups.
[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 (10)

Potency Measurements

ProteinTaxonomyMeasurementAverage (µ)Min (ref.)Avg (ref.)Max (ref.)Bioassay(s)
15-lipoxygenase, partialHomo sapiens (human)Potency39.81070.012610.691788.5700AID887
peroxisome proliferator activated receptor gammaHomo sapiens (human)Potency26.83250.001019.414170.9645AID743094
peripheral myelin protein 22Rattus norvegicus (Norway rat)Potency25.09990.005612.367736.1254AID624044
[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)
Glutamate receptor ionotropic, NMDA 1 Rattus norvegicus (Norway rat)IC50 (µMol)0.04000.00071.600310.0000AID144763
Glutamate receptor ionotropic, NMDA 2A Rattus norvegicus (Norway rat)IC50 (µMol)0.04000.00071.630610.0000AID144763
Glutamate receptor ionotropic, NMDA 2BRattus norvegicus (Norway rat)IC50 (µMol)0.04000.00061.525710.0000AID144763
Glutamate receptor ionotropic, NMDA 2CRattus norvegicus (Norway rat)IC50 (µMol)0.04000.00071.747210.0000AID144763
Glutamate receptor ionotropic, NMDA 2DRattus norvegicus (Norway rat)IC50 (µMol)0.04000.00071.741110.0000AID144763
Glutamate receptor ionotropic, NMDA 3BRattus norvegicus (Norway rat)IC50 (µMol)0.04000.00071.741110.0000AID144763
Glutamate receptor ionotropic, NMDA 3ARattus norvegicus (Norway rat)IC50 (µMol)0.04000.00071.741110.0000AID144763
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Ceullar Components (2)

Processvia Protein(s)Taxonomy
endoplasmic reticulum membraneGlutamate receptor ionotropic, NMDA 1 Rattus norvegicus (Norway rat)
plasma membraneGlutamate receptor ionotropic, NMDA 1 Rattus norvegicus (Norway rat)
endoplasmic reticulum membraneGlutamate receptor ionotropic, NMDA 2A Rattus norvegicus (Norway rat)
plasma membraneGlutamate receptor ionotropic, NMDA 2A Rattus norvegicus (Norway rat)
endoplasmic reticulum membraneGlutamate receptor ionotropic, NMDA 2BRattus norvegicus (Norway rat)
plasma membraneGlutamate receptor ionotropic, NMDA 2BRattus norvegicus (Norway rat)
endoplasmic reticulum membraneGlutamate receptor ionotropic, NMDA 2CRattus norvegicus (Norway rat)
plasma membraneGlutamate receptor ionotropic, NMDA 2CRattus norvegicus (Norway rat)
endoplasmic reticulum membraneGlutamate receptor ionotropic, NMDA 2DRattus norvegicus (Norway rat)
plasma membraneGlutamate receptor ionotropic, NMDA 2DRattus norvegicus (Norway rat)
endoplasmic reticulum membraneGlutamate receptor ionotropic, NMDA 3BRattus norvegicus (Norway rat)
plasma membraneGlutamate receptor ionotropic, NMDA 3BRattus norvegicus (Norway rat)
endoplasmic reticulum membraneGlutamate receptor ionotropic, NMDA 3ARattus norvegicus (Norway rat)
plasma membraneGlutamate receptor ionotropic, NMDA 3ARattus norvegicus (Norway rat)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (17)

Assay IDTitleYearJournalArticle
AID504749qHTS profiling for inhibitors of Plasmodium falciparum proliferation2011Science (New York, N.Y.), Aug-05, Volume: 333, Issue:6043
Chemical genomic profiling for antimalarial therapies, response signatures, and molecular targets.
AID1346986P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1296008Cytotoxic Profiling of Annotated Libraries Using Quantitative High-Throughput Screening2020SLAS discovery : advancing life sciences R & D, 01, Volume: 25, Issue:1
Cytotoxic Profiling of Annotated and Diverse Chemical Libraries Using Quantitative High-Throughput Screening.
AID1346987P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID146058Effective concentration against NR1/NR2A receptor2000Journal of medicinal chemistry, Jul-13, Volume: 43, Issue:14
Ligands for glutamate receptors: design and therapeutic prospects.
AID144763In vitro binding affinity for rat cortical membrane N-methyl-D-aspartate glutamate receptor determined using [3H]CPP as radioligand2003Journal of medicinal chemistry, Jul-03, Volume: 46, Issue:14
Synthesis and anticonvulsant activity of novel bicyclic acidic amino acids.
AID112826In vivo anticonvulsant activity determined as ip dose that blocked clonic seizures induced in DBA/2 mice by audiogenic stimuli2003Journal of medicinal chemistry, Jul-03, Volume: 46, Issue:14
Synthesis and anticonvulsant activity of novel bicyclic acidic amino acids.
AID112822In vivo anticonvulsant activity determined as ip dose that blocked NMDA-induced clonic seizures induced in DBA/2 mice2003Journal of medicinal chemistry, Jul-03, Volume: 46, Issue:14
Synthesis and anticonvulsant activity of novel bicyclic acidic amino acids.
AID112827In vivo anticonvulsant activity determined as ip dose that blocked tonic seizures induced by audiogenic stimuli in DBA/2 mice after pretreatment with D-serine2003Journal of medicinal chemistry, Jul-03, Volume: 46, Issue:14
Synthesis and anticonvulsant activity of novel bicyclic acidic amino acids.
AID112696In vivo anticonvulsant activity determined as ip dose that blocked 3,5-DHPG induced clonic seizures induced in DBA/2 mice2003Journal of medicinal chemistry, Jul-03, Volume: 46, Issue:14
Synthesis and anticonvulsant activity of novel bicyclic acidic amino acids.
AID112825In vivo anticonvulsant activity determined as ip dose that blocked clonic seizures induced by audiogenic stimuli in DBA/2 mice after pretreatment with D-serine2003Journal of medicinal chemistry, Jul-03, Volume: 46, Issue:14
Synthesis and anticonvulsant activity of novel bicyclic acidic amino acids.
AID146060Effective concentration against NR1/NR2B receptor2000Journal of medicinal chemistry, Jul-13, Volume: 43, Issue:14
Ligands for glutamate receptors: design and therapeutic prospects.
AID112828In vivo anticonvulsant activity determined as ip dose that blocked tonic seizures induced in DBA/2 mice by audiogenic stimuli2003Journal of medicinal chemistry, Jul-03, Volume: 46, Issue:14
Synthesis and anticonvulsant activity of novel bicyclic acidic amino acids.
AID112824In vivo anticonvulsant activity determined as ip dose that blocked NMDA-induced tonic seizures induced in DBA/2 mice after ip administration2003Journal of medicinal chemistry, Jul-03, Volume: 46, Issue:14
Synthesis and anticonvulsant activity of novel bicyclic acidic amino acids.
AID146062Effective concentration against NR1/NR2C receptor2000Journal of medicinal chemistry, Jul-13, Volume: 43, Issue:14
Ligands for glutamate receptors: design and therapeutic prospects.
AID112698In vivo anticonvulsant activity determined as ip dose that blocked 3,5-DHPG induced tonic seizures induced in DBA/2 mice after2003Journal of medicinal chemistry, Jul-03, Volume: 46, Issue:14
Synthesis and anticonvulsant activity of novel bicyclic acidic amino acids.
AID146064Effective concentration against NR1/NR2D receptor2000Journal of medicinal chemistry, Jul-13, Volume: 43, Issue:14
Ligands for glutamate receptors: design and therapeutic prospects.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (5)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's2 (40.00)29.6817
2010's2 (40.00)24.3611
2020's1 (20.00)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials0 (0.00%)5.53%
Reviews1 (20.00%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other4 (80.00%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]