Page last updated: 2024-12-07

paxilline

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Description

Paxilline is a tremorgenic mycotoxin produced by the fungus Penicillium paxilli. It is a potent inhibitor of the enzyme glycogen synthase kinase-3 (GSK-3), which plays a role in the regulation of various cellular processes, including cell growth, proliferation, and differentiation. Paxilline has been shown to induce tremors and other neurological symptoms in animals, and it is thought to be responsible for some cases of human poisoning. Its synthesis involves a complex series of enzymatic reactions, and it has been the subject of much research due to its potential as a tool for studying GSK-3 and its role in disease. The study of paxilline has led to the development of new inhibitors of GSK-3, which have potential therapeutic applications in the treatment of various diseases, including cancer, Alzheimer's disease, and diabetes.'

paxilline: structure given in first source; RN given refers to (2R-(2alpha,4bbeta,6aalpha,12bbeta,12calpha,14abeta))-isomer [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

paxilline : An indole diterpene alkaloid with formula C27H33NO4 isolated from Penicillium paxilli. It is a potent inhibitor of large conductance Ca2(+)- and voltage-activated K(+) (BK)-type channels. [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 CID105008
CHEMBL ID410063
CHEBI ID34907
SCHEMBL ID361232
MeSH IDM0138867

Synonyms (66)

Synonym
CBIOL_001842
HMS3268F05
BRD-K38251852-001-02-5
57186-25-1
smr000058863
MLS000028812 ,
paxilline
nsc-658707
2h-pyrano(2'',3'':5',6')benz(1',2':6,7)indeno(1,2-b)indol-3(4bh)-one, 5,6,6a,7,12,12b,12c,13,14,14a-decahydro-4b-hydroxy-2-(1-hydroxy-1-methylethyl)-12b,12c-dimethyl-, (2r,4bs,6as,12bs,12cr,14as)-
nsc 658707
2h-1-benzopyrano(5',6':6,7)indeno(1,2-b)indol-3(4bh)-one, 5,6,6a,7,12,12b,12c,13,14,14a-decahydro-4b-hydroxy-2-(1-hydroxy-1-methylethyl)-12b,12c-dimethyl-, (2-alpha,4b-beta,6a-alpha,12b-beta,12c-alpha,14a-beta)-
brn 5317894
BIO2_000627
BIO1_000128
BIO1_000617
BIO1_001106
BIO2_000147
BSPBIO_001427
paxilline, powder, >=98% (hplc)
KBIO2_005283
KBIO3_000293
KBIO2_002715
KBIO3_000294
KBIOSS_000147
KBIO2_000147
KBIOGR_000147
SPECTRUM5_001975
IDI1_033897
NCGC00025342-05
EDD20523-48C0-4594-B22A-1FE297F60611
HMS1989H09
CHEMBL410063
chebi:34907 ,
HMS1791H09
HMS1361H09
HMS2232J18
unii-3t9u9z96l7
3t9u9z96l7 ,
paxillin
KC-155
SCHEMBL361232
paxiline
(2r,4bs,6as,12bs,12cr,14as)-4b-hydroxy-2-(2-hydroxypropan-2-yl)-12b,12c-dimethyl-5,6,6a,7,12,12b,12c,13,14,14a-decahydro-2h-[1]benzopyrano[5',6':6,7]indeno[1,2-b]indol-3(4bh)-one
(+)-paxilline
(2r,4bs,6as,12bs,12cr,14as)-4b-hydroxy-2-(2-hydroxypropan-2-yl)-12b,12c-dimethyl-5,6,6a,7,12,12b,12c,13,14,14a-decahydro-2h-chromeno[5',6':6,7]indeno[1,2-b]indol-3(4bh)-one
(2r,4bs,6as,12bs,12cr,14as)-5,6,6a,7,12,12b,12c,13,14,14a-decahydro-4b-hydroxy-2-(1-hydroxy-1-methylethyl)-12b,12c-dimethyl-2h-pyrano[2'',3'':5',6']benz[1',2':6,7]indeno[1,2-b]indol-3(4bh)-one
bdbm50854
cid_105008
(2r,4bs,6as,12bs,12cr,14as)-5,6,6a, 7,12,12b,12c,13,14,14a-decahydro-4b-hydroxy-2-(1-h ydroxy-1-methylethyl)-12b,12c-dimethyl-2h-pyrano[2 '',3'':5',6']benz[1',2':6,7]indeno[1,2-b]indol-3(4bh)-one
c27h33no4
HB1056
AKOS024456907
HMS3402H09
sr-01000597527
SR-01000597527-1
NCGC00025342-07
ncgc00025342-07_c27h33no4_(2r,4bs,6as,12bs,12cr,14as)-4b-hydroxy-2-(2-hydroxy-2-propanyl)-12b,12c-dimethyl-5,6,6a,7,12,12b,12c,13,14,14a-decahydro-2h-chromeno[5',6':6,7]indeno[1,2-b]indol-3(4bh)-one
Q10860377
BRD-K38251852-001-06-6
1233509-81-3
2h-pyrano[2'',3'':5',6']benz[1',2':6,7]indeno[1,2-b]indol-3(4bh)-one, 5,6,6a,7,12,12b,12c,13,14,14a-decahydro-4b-hydroxy-2-(1-hydroxy-1-methylethyl)-12b,12c-dimethyl-, (2r,4bs,6as,12bs,12cr,14as)-rel-
DTXSID10972643
HY-N6778
CS-0026740
F82145
(1s,2r,5s,7r,11s,14s)-11-hydroxy-7-(2-hydroxypropan-2-yl)-1,2-dimethyl-6-oxa-23-azahexacyclo[12.10.0.02,11.05,10.016,24.017,22]tetracosa-9,16(24),17,19,21-pentaen-8-one

Research Excerpts

Overview

Paxilline (PAX) is a tremorgenic mycotoxin that has been found in perennial ryegrass infected with Acremonium lolii. Paxilline is a blocker of large-conductance Ca2+ -activated K+ (BKCa) channels.

ExcerptReferenceRelevance
"Paxilline is an indole-diterpene produced by Penicillium paxilli. "( Functional analysis of a prenyltransferase gene (paxD) in the paxilline biosynthetic gene cluster.
Dairi, T; Liu, C; Minami, A; Noike, M; Oikawa, H, 2014
)
2.09
"Paxilline (PAX) is a tremorgenic mycotoxin that has been found in perennial ryegrass infected with Acremonium lolii. "( Development and Evaluation of Monoclonal Antibodies for Paxilline.
Maragos, CM, 2015
)
2.11
"Paxilline is a blocker of large-conductance Ca2+ -activated K+ (BKCa) channels, while glibenclamide and pandinotoxin-Kalpha are blockers of ATP-sensitive and A-type K+ channels, respectively."( Glucocorticoids stimulate the activity of large-conductance Ca2+ -activated K+ channels in pituitary GH3 and AtT-20 cells via a non-genomic mechanism.
Huang, MH; Liu, YC; So, EC; Wu, SN, 2006
)
1.06

Treatment

ExcerptReferenceRelevance
"Paxilline treatment markedly upregulated DR5, a receptor of TRAIL, through a CHOP/GADD153-mediated process."( Paxilline enhances TRAIL-mediated apoptosis of glioma cells via modulation of c-FLIP, survivin and DR5.
Choi, KS; Kang, YJ; Kim, EH; Kim, IY; Kim, SU; Kwon, TK; Yoon, MJ, 2011
)
2.53

Toxicity

ExcerptReferenceRelevance
" Verrucosidin appeared to have the highest toxic potential, testing positive in both assays."( Genotoxicity assessment of five tremorgenic mycotoxins (fumitremorgen B, paxilline, penitrem A, verruculogen, and verrucosidin) produced by molds isolated from fermented meats.
Fink-Gremmels, J; Nijmeijer, S; Sabater-Vilar, M, 2003
)
0.55

Pharmacokinetics

ExcerptReferenceRelevance
" The distribution of CMAX proteins was dependent upon actin bundle organization."( Zyxin and vinculin distribution at the cell-extracellular matrix attachment complex (CMAX) in corneal epithelial tissue are actin dependent.
Ashrafzadeh, A; Jirawuthiworavong, G; Orlow, DL; Svoboda, KK, 1999
)
0.3

Bioavailability

ExcerptReferenceRelevance
" The small molecule, A-182086, an orally bioavailable ET(A/B)R antagonist, completely inhibited cell proliferation and tumor growth in KS IMM xenografts."( Endothelin receptor blockade inhibits molecular effectors of Kaposi's sarcoma cell invasion and tumor growth in vivo.
Albini, A; Bagnato, A; Di Castro, V; Natali, PG; Nicotra, MR; RosanĂ², L; Spinella, F, 2003
)
0.32
"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

Dosage Studied

ExcerptRelevanceReference
"In the present study, we have identified several proteins in Swiss 3T3 cells that are phosphorylated on tyrosine in response to platelet-derived growth factor (PDGF) and exhibit an unusual bell-shaped dose-response curve with a maximum at 5 ng/ml platelet-derived growth factor (PDGF)."( Platelet-derived growth factor modulation of focal adhesion kinase (p125FAK) and paxillin tyrosine phosphorylation in Swiss 3T3 cells. Bell-shaped dose response and cross-talk with bombesin.
Rankin, S; Rozengurt, E, 1994
)
0.29
" Furthermore, different dose-response relationships were obtained for tyrosine phosphorylation of focal adhesion proteins and for ERK activation in response to PDGF."( Tyrosine phosphorylation of p125(Fak), p130(Cas), and paxillin does not require extracellular signal-regulated kinase activation in Swiss 3T3 cells stimulated by bombesin or platelet-derived growth factor.
Leopoldt, D; Rozengurt, E; Saab, S; Yee, HF, 2000
)
0.31
" Addition of [d-Arg(1),d-Trp(5,7,9), Leu(11)]SP, at 10 micrometer, caused a striking rightward shift in the dose-response curves of DNA synthesis induced by bombesin, bradykinin, or vasopressin and markedly inhibited the activation of p42(mapk) (ERK-2) and p44(mapk) (ERK-1) induced by these GPCR agonists."( [D-Arg(1),D-Trp(5,7,9),Leu(11)]Substance P inhibits bombesin-induced mitogenic signal transduction mediated by both G(q) and G(12) in Swiss 3T3cells.
Duque, J; Rozengurt, E; Santiskulvong, C; Sinnett-Smith, J, 2000
)
0.31
" Dose-response curves were constructed, and the combination index (CI) for drug interaction was calculated."( Dasatinib (BMS-35482) interacts synergistically with docetaxel, gemcitabine, topotecan, and doxorubicin in ovarian cancer cells with high SRC pathway activation and protein expression.
Adams, DJ; Grace, L; Jia, J; Murphy, SK; Nixon, AB; Secord, AA; Teoh, D, 2014
)
0.4
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (8)

RoleDescription
mycotoxinPoisonous substance produced by fungi.
Penicillium metaboliteAny fungal metabolite produced during a metabolic reaction in Penicillium.
anticonvulsantA drug used to prevent seizures or reduce their severity.
Aspergillus metaboliteAny fungal metabolite produced during a metabolic reaction in the mould, Aspergillus.
potassium channel blockerAn agent that inhibits cell membrane glycoproteins that are selectively permeable to potassium ions.
genotoxinA role played by a chemical compound to induce direct or indirect DNA damage. Such damage can potentially lead to the formation of a malignant tumour, but DNA damage does not lead inevitably to the creation of cancerous cells.
geroprotectorAny compound that supports healthy aging, slows the biological aging process, or extends lifespan.
EC 3.6.3.8 (Ca(2+)-transporting ATPase) inhibitorAn EC 3.6.3.* (acid anhydride hydrolase catalysing transmembrane movement of substances) inhibitor that interferes with the action of Ca(2+)-transporting ATPase (EC 3.6.3.8).
[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
organic heterohexacyclic compound
tertiary alcoholA tertiary alcohol is a compound in which a hydroxy group, -OH, is attached to a saturated carbon atom which has three other carbon atoms attached to it.
terpenoid indole alkaloidAn indole alkaloid which is biosynthesised from L-tryptophan and isoprenoid building blocks.
enoneAn alpha,beta-unsaturated ketone of general formula R(1)R(2)C=CR(3)-C(=O)R(4) (R(4) =/= H) in which the C=O function is conjugated to a C=C double bond at the alpha,beta position.
diterpene alkaloid
[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]

Pathways (1)

PathwayProteinsCompounds
paxilline and diprenylpaxilline biosynthesis314

Protein Targets (26)

Potency Measurements

ProteinTaxonomyMeasurementAverage (µ)Min (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Chain A, Beta-lactamaseEscherichia coli K-12Potency25.11890.044717.8581100.0000AID485341
Chain A, JmjC domain-containing histone demethylation protein 3AHomo sapiens (human)Potency56.23410.631035.7641100.0000AID504339
glp-1 receptor, partialHomo sapiens (human)Potency14.12540.01846.806014.1254AID624417
TDP1 proteinHomo sapiens (human)Potency21.85280.000811.382244.6684AID686978; AID686979
Microtubule-associated protein tauHomo sapiens (human)Potency17.78280.180013.557439.8107AID1468
Smad3Homo sapiens (human)Potency35.48130.00527.809829.0929AID588855
67.9K proteinVaccinia virusPotency11.22020.00018.4406100.0000AID720579
bromodomain adjacent to zinc finger domain 2BHomo sapiens (human)Potency35.48130.707936.904389.1251AID504333
IDH1Homo sapiens (human)Potency16.36010.005210.865235.4813AID686970
euchromatic histone-lysine N-methyltransferase 2Homo sapiens (human)Potency31.62280.035520.977089.1251AID504332
huntingtin isoform 2Homo sapiens (human)Potency31.62280.000618.41981,122.0200AID1688
histone-lysine N-methyltransferase 2A isoform 2 precursorHomo sapiens (human)Potency39.81070.010323.856763.0957AID2662
peptidyl-prolyl cis-trans isomerase NIMA-interacting 1Homo sapiens (human)Potency35.48130.425612.059128.1838AID504891
tumor susceptibility gene 101 proteinHomo sapiens (human)Potency25.11890.129810.833132.6090AID493005
gemininHomo sapiens (human)Potency1.39520.004611.374133.4983AID624296; AID624297
DNA dC->dU-editing enzyme APOBEC-3F isoform aHomo sapiens (human)Potency31.62280.025911.239831.6228AID602313
neuropeptide S receptor isoform AHomo sapiens (human)Potency10.00000.015812.3113615.5000AID1461
TAR DNA-binding protein 43Homo sapiens (human)Potency22.38721.778316.208135.4813AID652104
[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)
TPA: protein transporter TIM10Saccharomyces cerevisiae S288CIC50 (µMol)33.55000.580026.547675.8000AID493003
Sarcoplasmic/endoplasmic reticulum calcium ATPase 1Oryctolagus cuniculus (rabbit)IC50 (µMol)5.00000.00022.81679.0000AID1605047
Sarcoplasmic/endoplasmic reticulum calcium ATPase 2Homo sapiens (human)IC50 (µMol)5.00000.09003.52257.0000AID1605059
Sarcoplasmic/endoplasmic reticulum calcium ATPase 3Homo sapiens (human)IC50 (µMol)5.00000.09003.52257.0000AID1605060
BZLF2Human herpesvirus 4 type 2 (Epstein-Barr virus type 2)IC50 (µMol)2.03000.42004.434216.2300AID1419
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Activation Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
POsterior SegregationCaenorhabditis elegansEC50 (µMol)16.71902.201047.1808186.6810AID1964
Sodium-dependent noradrenaline transporter Homo sapiens (human)EC50 (µMol)12.27200.082031.0243168.9080AID1960
Zinc finger protein mex-5Caenorhabditis elegansEC50 (µMol)12.27200.082033.5679168.9080AID1960
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (62)

Processvia Protein(s)Taxonomy
autophagosome assemblySarcoplasmic/endoplasmic reticulum calcium ATPase 2Homo sapiens (human)
regulation of the force of heart contractionSarcoplasmic/endoplasmic reticulum calcium ATPase 2Homo sapiens (human)
intracellular calcium ion homeostasisSarcoplasmic/endoplasmic reticulum calcium ATPase 2Homo sapiens (human)
ER-nucleus signaling pathwaySarcoplasmic/endoplasmic reticulum calcium ATPase 2Homo sapiens (human)
cell adhesionSarcoplasmic/endoplasmic reticulum calcium ATPase 2Homo sapiens (human)
epidermis developmentSarcoplasmic/endoplasmic reticulum calcium ATPase 2Homo sapiens (human)
positive regulation of heart rateSarcoplasmic/endoplasmic reticulum calcium ATPase 2Homo sapiens (human)
positive regulation of cardiac muscle cell apoptotic processSarcoplasmic/endoplasmic reticulum calcium ATPase 2Homo sapiens (human)
transition between fast and slow fiberSarcoplasmic/endoplasmic reticulum calcium ATPase 2Homo sapiens (human)
cardiac muscle hypertrophy in response to stressSarcoplasmic/endoplasmic reticulum calcium ATPase 2Homo sapiens (human)
autophagosome membrane dockingSarcoplasmic/endoplasmic reticulum calcium ATPase 2Homo sapiens (human)
endoplasmic reticulum calcium ion homeostasisSarcoplasmic/endoplasmic reticulum calcium ATPase 2Homo sapiens (human)
positive regulation of endoplasmic reticulum calcium ion concentrationSarcoplasmic/endoplasmic reticulum calcium ATPase 2Homo sapiens (human)
T-tubule organizationSarcoplasmic/endoplasmic reticulum calcium ATPase 2Homo sapiens (human)
monoatomic ion transmembrane transportSarcoplasmic/endoplasmic reticulum calcium ATPase 2Homo sapiens (human)
cellular response to oxidative stressSarcoplasmic/endoplasmic reticulum calcium ATPase 2Homo sapiens (human)
response to endoplasmic reticulum stressSarcoplasmic/endoplasmic reticulum calcium ATPase 2Homo sapiens (human)
negative regulation of heart contractionSarcoplasmic/endoplasmic reticulum calcium ATPase 2Homo sapiens (human)
neuron cellular homeostasisSarcoplasmic/endoplasmic reticulum calcium ATPase 2Homo sapiens (human)
sarcoplasmic reticulum calcium ion transportSarcoplasmic/endoplasmic reticulum calcium ATPase 2Homo sapiens (human)
calcium ion transmembrane transportSarcoplasmic/endoplasmic reticulum calcium ATPase 2Homo sapiens (human)
regulation of cardiac muscle cell membrane potentialSarcoplasmic/endoplasmic reticulum calcium ATPase 2Homo sapiens (human)
regulation of cardiac muscle cell action potential involved in regulation of contractionSarcoplasmic/endoplasmic reticulum calcium ATPase 2Homo sapiens (human)
organelle localization by membrane tetheringSarcoplasmic/endoplasmic reticulum calcium ATPase 2Homo sapiens (human)
negative regulation of receptor bindingSarcoplasmic/endoplasmic reticulum calcium ATPase 2Homo sapiens (human)
regulation of calcium ion-dependent exocytosis of neurotransmitterSarcoplasmic/endoplasmic reticulum calcium ATPase 2Homo sapiens (human)
calcium ion transport from cytosol to endoplasmic reticulumSarcoplasmic/endoplasmic reticulum calcium ATPase 2Homo sapiens (human)
regulation of cardiac conductionSarcoplasmic/endoplasmic reticulum calcium ATPase 2Homo sapiens (human)
calcium ion import into sarcoplasmic reticulumSarcoplasmic/endoplasmic reticulum calcium ATPase 2Homo sapiens (human)
mitochondrion-endoplasmic reticulum membrane tetheringSarcoplasmic/endoplasmic reticulum calcium ATPase 2Homo sapiens (human)
regulation of cardiac muscle contraction by calcium ion signalingSarcoplasmic/endoplasmic reticulum calcium ATPase 2Homo sapiens (human)
monoamine transportSodium-dependent noradrenaline transporter Homo sapiens (human)
neurotransmitter transportSodium-dependent noradrenaline transporter Homo sapiens (human)
chemical synaptic transmissionSodium-dependent noradrenaline transporter Homo sapiens (human)
response to xenobiotic stimulusSodium-dependent noradrenaline transporter Homo sapiens (human)
response to painSodium-dependent noradrenaline transporter Homo sapiens (human)
norepinephrine uptakeSodium-dependent noradrenaline transporter Homo sapiens (human)
neuron cellular homeostasisSodium-dependent noradrenaline transporter Homo sapiens (human)
amino acid transportSodium-dependent noradrenaline transporter Homo sapiens (human)
norepinephrine transportSodium-dependent noradrenaline transporter Homo sapiens (human)
dopamine uptake involved in synaptic transmissionSodium-dependent noradrenaline transporter Homo sapiens (human)
sodium ion transmembrane transportSodium-dependent noradrenaline transporter Homo sapiens (human)
negative regulation of protein phosphorylationTAR DNA-binding protein 43Homo sapiens (human)
mRNA processingTAR DNA-binding protein 43Homo sapiens (human)
RNA splicingTAR DNA-binding protein 43Homo sapiens (human)
negative regulation of gene expressionTAR DNA-binding protein 43Homo sapiens (human)
regulation of protein stabilityTAR DNA-binding protein 43Homo sapiens (human)
positive regulation of insulin secretionTAR DNA-binding protein 43Homo sapiens (human)
response to endoplasmic reticulum stressTAR DNA-binding protein 43Homo sapiens (human)
positive regulation of protein import into nucleusTAR DNA-binding protein 43Homo sapiens (human)
regulation of circadian rhythmTAR DNA-binding protein 43Homo sapiens (human)
regulation of apoptotic processTAR DNA-binding protein 43Homo sapiens (human)
negative regulation by host of viral transcriptionTAR DNA-binding protein 43Homo sapiens (human)
rhythmic processTAR DNA-binding protein 43Homo sapiens (human)
regulation of cell cycleTAR DNA-binding protein 43Homo sapiens (human)
3'-UTR-mediated mRNA destabilizationTAR DNA-binding protein 43Homo sapiens (human)
3'-UTR-mediated mRNA stabilizationTAR DNA-binding protein 43Homo sapiens (human)
nuclear inner membrane organizationTAR DNA-binding protein 43Homo sapiens (human)
amyloid fibril formationTAR DNA-binding protein 43Homo sapiens (human)
regulation of gene expressionTAR DNA-binding protein 43Homo sapiens (human)
calcium ion transportSarcoplasmic/endoplasmic reticulum calcium ATPase 3Homo sapiens (human)
intracellular calcium ion homeostasisSarcoplasmic/endoplasmic reticulum calcium ATPase 3Homo sapiens (human)
activation of cysteine-type endopeptidase activity involved in apoptotic processSarcoplasmic/endoplasmic reticulum calcium ATPase 3Homo sapiens (human)
monoatomic ion transmembrane transportSarcoplasmic/endoplasmic reticulum calcium ATPase 3Homo sapiens (human)
intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stressSarcoplasmic/endoplasmic reticulum calcium ATPase 3Homo sapiens (human)
calcium ion transmembrane transportSarcoplasmic/endoplasmic reticulum calcium ATPase 3Homo sapiens (human)
transport across blood-brain barrierSarcoplasmic/endoplasmic reticulum calcium ATPase 3Homo sapiens (human)
negative regulation of receptor bindingSarcoplasmic/endoplasmic reticulum calcium ATPase 3Homo sapiens (human)
calcium ion transport from cytosol to endoplasmic reticulumSarcoplasmic/endoplasmic reticulum calcium ATPase 3Homo sapiens (human)
regulation of cardiac conductionSarcoplasmic/endoplasmic reticulum calcium ATPase 3Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (31)

Processvia Protein(s)Taxonomy
P-type calcium transporter activitySarcoplasmic/endoplasmic reticulum calcium ATPase 2Homo sapiens (human)
calcium ion bindingSarcoplasmic/endoplasmic reticulum calcium ATPase 2Homo sapiens (human)
protein bindingSarcoplasmic/endoplasmic reticulum calcium ATPase 2Homo sapiens (human)
ATP bindingSarcoplasmic/endoplasmic reticulum calcium ATPase 2Homo sapiens (human)
ATP hydrolysis activitySarcoplasmic/endoplasmic reticulum calcium ATPase 2Homo sapiens (human)
enzyme bindingSarcoplasmic/endoplasmic reticulum calcium ATPase 2Homo sapiens (human)
transmembrane transporter bindingSarcoplasmic/endoplasmic reticulum calcium ATPase 2Homo sapiens (human)
S100 protein bindingSarcoplasmic/endoplasmic reticulum calcium ATPase 2Homo sapiens (human)
P-type calcium transporter activity involved in regulation of cardiac muscle cell membrane potentialSarcoplasmic/endoplasmic reticulum calcium ATPase 2Homo sapiens (human)
lncRNA bindingSarcoplasmic/endoplasmic reticulum calcium ATPase 2Homo sapiens (human)
actin bindingSodium-dependent noradrenaline transporter Homo sapiens (human)
neurotransmitter transmembrane transporter activitySodium-dependent noradrenaline transporter Homo sapiens (human)
neurotransmitter:sodium symporter activitySodium-dependent noradrenaline transporter Homo sapiens (human)
dopamine:sodium symporter activitySodium-dependent noradrenaline transporter Homo sapiens (human)
norepinephrine:sodium symporter activitySodium-dependent noradrenaline transporter Homo sapiens (human)
protein bindingSodium-dependent noradrenaline transporter Homo sapiens (human)
monoamine transmembrane transporter activitySodium-dependent noradrenaline transporter Homo sapiens (human)
alpha-tubulin bindingSodium-dependent noradrenaline transporter Homo sapiens (human)
metal ion bindingSodium-dependent noradrenaline transporter Homo sapiens (human)
beta-tubulin bindingSodium-dependent noradrenaline transporter Homo sapiens (human)
RNA polymerase II cis-regulatory region sequence-specific DNA bindingTAR DNA-binding protein 43Homo sapiens (human)
DNA bindingTAR DNA-binding protein 43Homo sapiens (human)
double-stranded DNA bindingTAR DNA-binding protein 43Homo sapiens (human)
RNA bindingTAR DNA-binding protein 43Homo sapiens (human)
mRNA 3'-UTR bindingTAR DNA-binding protein 43Homo sapiens (human)
protein bindingTAR DNA-binding protein 43Homo sapiens (human)
lipid bindingTAR DNA-binding protein 43Homo sapiens (human)
identical protein bindingTAR DNA-binding protein 43Homo sapiens (human)
pre-mRNA intronic bindingTAR DNA-binding protein 43Homo sapiens (human)
molecular condensate scaffold activityTAR DNA-binding protein 43Homo sapiens (human)
P-type calcium transporter activitySarcoplasmic/endoplasmic reticulum calcium ATPase 3Homo sapiens (human)
protein bindingSarcoplasmic/endoplasmic reticulum calcium ATPase 3Homo sapiens (human)
ATP bindingSarcoplasmic/endoplasmic reticulum calcium ATPase 3Homo sapiens (human)
cysteine-type endopeptidase activator activity involved in apoptotic processSarcoplasmic/endoplasmic reticulum calcium ATPase 3Homo sapiens (human)
calcium ion transmembrane transporter activitySarcoplasmic/endoplasmic reticulum calcium ATPase 3Homo sapiens (human)
ATP hydrolysis activitySarcoplasmic/endoplasmic reticulum calcium ATPase 3Homo sapiens (human)
calcium-dependent ATPase activitySarcoplasmic/endoplasmic reticulum calcium ATPase 3Homo sapiens (human)
transmembrane transporter bindingSarcoplasmic/endoplasmic reticulum calcium ATPase 3Homo sapiens (human)
metal ion bindingSarcoplasmic/endoplasmic reticulum calcium ATPase 3Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (23)

Processvia Protein(s)Taxonomy
endoplasmic reticulumSarcoplasmic/endoplasmic reticulum calcium ATPase 2Homo sapiens (human)
endoplasmic reticulum membraneSarcoplasmic/endoplasmic reticulum calcium ATPase 2Homo sapiens (human)
plasma membraneSarcoplasmic/endoplasmic reticulum calcium ATPase 2Homo sapiens (human)
membraneSarcoplasmic/endoplasmic reticulum calcium ATPase 2Homo sapiens (human)
sarcoplasmic reticulumSarcoplasmic/endoplasmic reticulum calcium ATPase 2Homo sapiens (human)
platelet dense tubular network membraneSarcoplasmic/endoplasmic reticulum calcium ATPase 2Homo sapiens (human)
sarcoplasmic reticulum membraneSarcoplasmic/endoplasmic reticulum calcium ATPase 2Homo sapiens (human)
ribbon synapseSarcoplasmic/endoplasmic reticulum calcium ATPase 2Homo sapiens (human)
membraneSarcoplasmic/endoplasmic reticulum calcium ATPase 2Homo sapiens (human)
plasma membraneSodium-dependent noradrenaline transporter Homo sapiens (human)
cell surfaceSodium-dependent noradrenaline transporter Homo sapiens (human)
membraneSodium-dependent noradrenaline transporter Homo sapiens (human)
neuronal cell body membraneSodium-dependent noradrenaline transporter Homo sapiens (human)
presynaptic membraneSodium-dependent noradrenaline transporter Homo sapiens (human)
plasma membraneSodium-dependent noradrenaline transporter Homo sapiens (human)
axonSodium-dependent noradrenaline transporter Homo sapiens (human)
intracellular non-membrane-bounded organelleTAR DNA-binding protein 43Homo sapiens (human)
nucleusTAR DNA-binding protein 43Homo sapiens (human)
nucleoplasmTAR DNA-binding protein 43Homo sapiens (human)
perichromatin fibrilsTAR DNA-binding protein 43Homo sapiens (human)
mitochondrionTAR DNA-binding protein 43Homo sapiens (human)
cytoplasmic stress granuleTAR DNA-binding protein 43Homo sapiens (human)
nuclear speckTAR DNA-binding protein 43Homo sapiens (human)
interchromatin granuleTAR DNA-binding protein 43Homo sapiens (human)
nucleoplasmTAR DNA-binding protein 43Homo sapiens (human)
chromatinTAR DNA-binding protein 43Homo sapiens (human)
endoplasmic reticulumSarcoplasmic/endoplasmic reticulum calcium ATPase 3Homo sapiens (human)
endoplasmic reticulum membraneSarcoplasmic/endoplasmic reticulum calcium ATPase 3Homo sapiens (human)
sarcoplasmic reticulumSarcoplasmic/endoplasmic reticulum calcium ATPase 3Homo sapiens (human)
organelle membraneSarcoplasmic/endoplasmic reticulum calcium ATPase 3Homo sapiens (human)
platelet dense tubular network membraneSarcoplasmic/endoplasmic reticulum calcium ATPase 3Homo sapiens (human)
nuclear membraneSarcoplasmic/endoplasmic reticulum calcium ATPase 3Homo sapiens (human)
sarcoplasmic reticulum membraneSarcoplasmic/endoplasmic reticulum calcium ATPase 3Homo sapiens (human)
membraneSarcoplasmic/endoplasmic reticulum calcium ATPase 3Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (40)

Assay IDTitleYearJournalArticle
AID324585Increase in long-lived protein degradation in human H4 cells after 24 hrs relative to control2007Proceedings of the National Academy of Sciences of the United States of America, Nov-27, Volume: 104, Issue:48
Small molecule regulators of autophagy identified by an image-based high-throughput screen.
AID1605047Inhibition of rabbit skeletal muscle microsomes SERCA1a by enzyme-coupled method2020Journal of medicinal chemistry, 03-12, Volume: 63, Issue:5
Sarco/Endoplasmic Reticulum Calcium ATPase Inhibitors: Beyond Anticancer Perspective.
AID1605059Inhibition of SERCA2b in human platelet microsomes by enzyme-coupled method2020Journal of medicinal chemistry, 03-12, Volume: 63, Issue:5
Sarco/Endoplasmic Reticulum Calcium ATPase Inhibitors: Beyond Anticancer Perspective.
AID336866Induction of electrically-stimulated guinea pig ileum contraction at 1 ug/ml relative to control in presence of acetylcholine
AID324429Increase in light chain 3-GFP+ autophagosome vesicle number per cell in human H4 cells at 5.7 uM after 24 hrs by high throughput fluorescence microscopy relative to control2007Proceedings of the National Academy of Sciences of the United States of America, Nov-27, Volume: 104, Issue:48
Small molecule regulators of autophagy identified by an image-based high-throughput screen.
AID336869Induction of electrically-stimulated guinea pig ileum twitch contraction at 1 ug/ml relative to control in presence of hyoscine
AID324481Increase in light chain 3-GFP+ autophagosome vesicle area per cell in human H4 cells at 5.7 uM after 24 hrs by high throughput fluorescence microscopy relative to control2007Proceedings of the National Academy of Sciences of the United States of America, Nov-27, Volume: 104, Issue:48
Small molecule regulators of autophagy identified by an image-based high-throughput screen.
AID324584Increase in long-lived protein degradation in human H4 cells after 4 hrs relative to control2007Proceedings of the National Academy of Sciences of the United States of America, Nov-27, Volume: 104, Issue:48
Small molecule regulators of autophagy identified by an image-based high-throughput screen.
AID324577Effect on FYVE-RFP+ vesicle intensity per cell in human H4 cells after 4 hrs relative to control2007Proceedings of the National Academy of Sciences of the United States of America, Nov-27, Volume: 104, Issue:48
Small molecule regulators of autophagy identified by an image-based high-throughput screen.
AID336861Induction of guinea pig ileum contraction
AID336867Induction of electrically-stimulated guinea pig ileum twitch contraction at 10 ng/ml relative to control in presence of hyoscine
AID324583Increase in long-lived protein degradation in human H4 cells after 2 hrs relative to control2007Proceedings of the National Academy of Sciences of the United States of America, Nov-27, Volume: 104, Issue:48
Small molecule regulators of autophagy identified by an image-based high-throughput screen.
AID324576Effect on FYVE-RFP+ vesicle intensity per cell in human H4 cells after 2 hrs relative to control2007Proceedings of the National Academy of Sciences of the United States of America, Nov-27, Volume: 104, Issue:48
Small molecule regulators of autophagy identified by an image-based high-throughput screen.
AID1605048Inhibition of porcine cerebellar microsomes SERCA2b by enzyme-coupled method2020Journal of medicinal chemistry, 03-12, Volume: 63, Issue:5
Sarco/Endoplasmic Reticulum Calcium ATPase Inhibitors: Beyond Anticancer Perspective.
AID1605060Inhibition of SERCA3 in human platelet microsomes by enzyme-coupled method2020Journal of medicinal chemistry, 03-12, Volume: 63, Issue:5
Sarco/Endoplasmic Reticulum Calcium ATPase Inhibitors: Beyond Anticancer Perspective.
AID336868Induction of electrically-stimulated guinea pig ileum twitch contraction at 100 ng/ml relative to control in presence of hyoscine
AID336865Induction of electrically-stimulated guinea pig ileum contraction at 100 ng/ml relative to control in presence of acetylcholine
AID324533Increase in light chain 3-GFP+ autophagosome vesicle intensity per cell in human H4 cells at 5.7 uM after 24 hrs by high throughput fluorescence microscopy relative to control2007Proceedings of the National Academy of Sciences of the United States of America, Nov-27, Volume: 104, Issue:48
Small molecule regulators of autophagy identified by an image-based high-throughput screen.
AID336863Tremorgenic activity in ip dosed mouse
AID1605058Inhibition of porcine cardiac microsomes SERCA2a by enzyme-coupled method2020Journal of medicinal chemistry, 03-12, Volume: 63, Issue:5
Sarco/Endoplasmic Reticulum Calcium ATPase Inhibitors: Beyond Anticancer Perspective.
AID324582Increase in long-lived protein degradation in human H4 cells after 1 hr relative to control2007Proceedings of the National Academy of Sciences of the United States of America, Nov-27, Volume: 104, Issue:48
Small molecule regulators of autophagy identified by an image-based high-throughput screen.
AID762954Antiviral activity against Influenza A virus (A/Puerto Rico/8/34(H1N1)) PR/8 infected in MDCK cells assessed as protection against virus-induced cytopathogenicity after 48 hrs by crystal-violet staining-based assay2013Journal of natural products, Jul-26, Volume: 76, Issue:7
Indole-diterpenoids with anti-H1N1 activity from the aciduric fungus Penicillium camemberti OUCMDZ-1492.
AID1721333Inhibition of TNP-ADP binding to SERCA (unknown origin) by UV dual-wavelength spectrophotometer2020Bioorganic & medicinal chemistry, 08-15, Volume: 28, Issue:16
Modulation of TRPV4 and BKCa for treatment of brain diseases.
AID324377Induction of light chain 3-GFP level in human H4 cells at 5.7 uM after 24 hrs by high throughput fluorescence microscopy relative to control2007Proceedings of the National Academy of Sciences of the United States of America, Nov-27, Volume: 104, Issue:48
Small molecule regulators of autophagy identified by an image-based high-throughput screen.
AID336864Induction of electrically-stimulated guinea pig ileum contraction at 10 ng/ml relative to control in presence of acetylcholine
AID324578Effect on FYVE-RFP+ vesicle intensity per cell in human H4 cells after 8 hrs relative to control2007Proceedings of the National Academy of Sciences of the United States of America, Nov-27, Volume: 104, Issue:48
Small molecule regulators of autophagy identified by an image-based high-throughput screen.
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.
AID1745845Primary qHTS for Inhibitors of ATXN expression
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
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.
AID1347159Primary screen GU Rhodamine qHTS for Zika virus inhibitors: Unlinked NS2B-NS3 protease assay2020Proceedings 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.
AID1347161Confirmatory screen NINDS Rhodamine 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.
AID1347157Confirmatory screen GU Rhodamine qHTS for Zika virus inhibitors qHTS2020Proceedings 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.
AID1347160Primary screen NINDS Rhodamine 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.
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.
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.
AID1347169Tertiary RLuc qRT-PCR qHTS assay 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.
AID588519A screen for compounds that inhibit viral RNA polymerase binding and polymerization activities2011Antiviral research, Sep, Volume: 91, Issue:3
High-throughput screening identification of poliovirus RNA-dependent RNA polymerase inhibitors.
AID540299A screen for compounds that inhibit the MenB enzyme of Mycobacterium tuberculosis2010Bioorganic & medicinal chemistry letters, Nov-01, Volume: 20, Issue:21
Synthesis and SAR studies of 1,4-benzoxazine MenB inhibitors: novel antibacterial agents against Mycobacterium tuberculosis.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (2,052)

TimeframeStudies, This Drug (%)All Drugs %
pre-19902 (0.10)18.7374
1990's336 (16.37)18.2507
2000's843 (41.08)29.6817
2010's732 (35.67)24.3611
2020's139 (6.77)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 33.93

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 moderate demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index33.93 (24.57)
Research Supply Index7.65 (2.92)
Research Growth Index6.91 (4.65)
Search Engine Demand Index45.55 (26.88)
Search Engine Supply Index1.94 (0.95)

This Compound (33.93)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials3 (0.14%)5.53%
Reviews76 (3.62%)6.00%
Case Studies1 (0.05%)4.05%
Observational1 (0.05%)0.25%
Other2,016 (96.14%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]