Page last updated: 2024-12-10

4-hydroxy-2-nonenal

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

Description

4-hydroxy-2-nonenal: cytotoxic product from peroxidation of liver microsomal lipids; RN given refers to cpd without isomeric designation [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

4-hydroxynon-2-enal : An enal consisting of non-2-ene having an oxo group at the 1-position and a hydroxy group at the 4-position. [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]

4-hydroxynonenal : A monounsaturated fatty aldehyde that is nonanal that has undergone dehydrogenation to introduce a double bond at any position in the aliphatic chain and in which a hydrogen at position 4 has been replaced by a hydroxy group. [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 CID5283344
CHEMBL ID454280
CHEBI ID58968
CHEBI ID32585
SCHEMBL ID3920
MeSH IDM0089511

Synonyms (63)

Synonym
chebi:58968 ,
(e)-4-hydroxynon-2-enal ,
(e)-4-hydroxy-2-nonenal
BRD-A15914070-001-01-5
ccris 1781
trans-4-hydroxy-2-nonenal
4-hydroxynon-2-enal
CHEBI:32585 ,
HNE ,
4-hydroxy-2,3-nonenal
4-hydroxy-2-nonenal
29343-52-0
4-hydroxynonenal
4-hne
4hne
HSCI1_000340
LMFA06000051
4-hydroxy-2e-nonenal
SMP2_000061
NCGC00161254-01
ccris 9028
2-nonenal, 4-hydroxy-
(2e)-4-hydroxynon-2-enal
75899-68-2
bdbm50242402
(+/-)4-hydroxynon-2-enal
BML1-C09
CHEMBL454280 ,
NCGC00161254-02
AKOS006274954
ccris 6927
128946-65-6
(e)-4-hydroxynonenal
M01859
unii-k1cvm13f96
k1cvm13f96 ,
tox21_113063
cas-75899-68-2
dtxsid4040395 ,
(2e)-4-hydroxy-2-nonenal
dtxcid2020395
gtpl6274
4-hydroxy-2-trans-nonenal
2-nonenal, 4-hydroxy-, (2e)-
hne [mi]
4-hydroxy-2-nonenal, trans-
SCHEMBL3920
(.+/-.)-4-hydroxy-2e-nonenal
JVJFIQYAHPMBBX-FNORWQNLSA-N
HMS3648N14
trans-4-hydroxynonan-2-enal
J-525023
C21642
mfcd00211020
Q229982
SR-01000946534-1
sr-01000946534
EX-A5735
CS-0061995
HY-113466
AC8369
MS-22883
PD021010

Research Excerpts

Toxicity

ExcerptReferenceRelevance
" The results showed that the peroxide was more toxic than HNE and much more than MDA."( Cytotoxicity of linoleic acid peroxide, malondialdehyde and 4-hydroxynonenal towards human fibroblasts.
Michiels, C; Remacle, J, 1991
)
0.28
" These results provide further support for the hypothesis that toxic aldehydic byproducts of lipid peroxidation contribute to hyperoxic injury."( Replacement of media in cell culture alters oxygen toxicity: possible role of lipid aldehydes and glutathione transferase in oxygen toxicity.
Roberts, RJ; Spitz, DR; Sullivan, SJ, 1991
)
0.28
" Both substances were found to be more toxic against neuroblastoma cells than against hematopoietic stem cells."( Cytotoxic effects of 6-hydroxydopamine, merocyanine-540 and related compounds on human neuroblastoma and hematopoietic stem cells.
Bruchelt, G; Esterbauer, H; Grygar, G; Niethammer, D; Treuner, J, 1989
)
0.28
" Trans, trans-muconaldehyde is a newly found microsomal metabolite of benzene, and trans-4-hydroxynonenal is a toxic aldehyde formed endogenously during lipid peroxidation."( Mutagenicity and toxicity studies of several alpha,beta-unsaturated aldehydes in the Salmonella typhimurium mutagenicity assay.
Cooper, KO; Witmer, CM; Witz, G, 1987
)
0.27
" The free radical dependence of beta-amyloid-associated toxicity was confirmed by the ability of the free radical scavenger vitamin E to prevent the toxic effects of Abeta."( The free radical antioxidant vitamin E protects cortical synaptosomal membranes from amyloid beta-peptide(25-35) toxicity but not from hydroxynonenal toxicity: relevance to the free radical hypothesis of Alzheimer's disease.
Butterfield, DA; Drake, J; Green, M; Jordan, B; Koppal, T; Subramaniam, R; Yatin, S, 1998
)
0.3
" Four-hydroxynonenal is toxic to cultured neurons and to the brain of experimental animals."( Glutathione transferase protects neuronal cultures against four hydroxynonenal toxicity.
Lovell, MA; Markesbery, WR; Xie, C, 1998
)
0.3
" Since melatonin, the main secretory product of the pineal gland, has been shown to protect against a number of toxic agents, it was given 30 min before 2-NP to test its protective effect against 2-NP toxicity."( 2-Nitropropane-induced lipid peroxidation: antitoxic effects of melatonin.
El-Sokkary, GH; Kim, SJ; Qi, W; Reiter, RJ; Rouvier Garay, MV; Tan, DX, 1998
)
0.3
" It is observed that the toxic manifestations of Fe-NTA gradually increase with the increasing age of animals."( Age-dependent renal accumulation of 4-hydroxy-2-nonenal (HNE)-modified proteins following parenteral administration of ferric nitrilotriacetate commensurate with its differential toxicity: implications for the involvement of HNE-protein adducts in oxidati
Alam, MS; Athar, M; Giri, DK; Giri, U; Iqbal, M, 1999
)
0.58
"4-Hydroxynonenal (4HNE) is the most prevalent toxic lipid peroxidation product formed during oxidative stress."( Multidrug resistance protein MRP1 protects against the toxicity of the major lipid peroxidation product 4-hydroxynonenal.
de Vries, EE; Hooiveld, GJ; Jansen, PL; Krikken, I; Müller, M; Renes, J, 2000
)
0.31
"4-Hydroxy-trans-2,3-nonenal (HNE) is a toxic end product of lipid peroxidation."( Multidrug resistance-associated protein 2 (MRP2) enhances 4-hydroxynonenal-induced toxicity in Madin-Darby canine kidney II cells.
Horie, T; Ito, K; Ji, B, 2004
)
0.32
" These results are discussed with reference to potential use of this redox cycling chemotheraputic agent in the treatement of cancer and its chemobrain side effect in brain."( Free radical mediated oxidative stress and toxic side effects in brain induced by the anti cancer drug adriamycin: insight into chemobrain.
Butterfield, DA; Cole, MP; Estus, S; Joshi, G; St Clair, DK; Sultana, R; Tangpong, J; Vore, M, 2005
)
0.33
" It has been shown to metabolize 4-hydroxynonenal (4-HNE) with high catalytic efficiency through its conjugation to glutathione (GSH) and has been suggested to be a major component of cellular defense against toxic electrophiles such as 4-HNE generated during LPO."( The course of CCl4 induced hepatotoxicity is altered in mGSTA4-4 null (-/-) mice.
Awasthi, YC; Boor, PJ; Ceci, JD; Dwivedi, S; Sharma, A; Sharma, R; Zimniak, P, 2006
)
0.33
"4-hydroxy-trans-2-nonenal (HNE) is one of the most abundant and toxic lipid aldehydes formed during lipid peroxidation by reactive oxygen species."( Glutathione level regulates HNE-induced genotoxicity in human erythroleukemia cells.
Awasthi, YC; Ramana, KV; Srivastava, SK; Yadav, UC, 2008
)
0.35
" Inhibition of MEK1/ERK mitogen-activated protein kinases significantly suppressed atRA-induced NRF2 activation and ARE-regulated gene expression, reducing cell resistance against toxic concentrations of RA."( NRF2 as a determinant of cellular resistance in retinoic acid cytotoxicity.
Ito, S; Kosuge, K; Tan, KP; Yang, M, 2008
)
0.35
" They also suffer a range of toxic insults, being a chief target of prooxidants such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 1-methyl-4-phenylpyridinium (MPP(+)), 6-hydroxydopamine (6-OHDA), 4-hydroxy-2-nonenal (HNE), and acrolein."( Cruciferous nutraceutical 3H-1,2-dithiole-3-thione protects human primary astrocytes against neurocytotoxicity elicited by MPTP, MPP(+), 6-OHDA, HNE and acrolein.
Jia, Z; Li, Y; Misra, HP; Zhu, H, 2009
)
0.54
"In premature infants, glucocorticoids ameliorate chronic lung disease, but have adverse effects on growth and the cardiovascular system."( Investigation of the use of antioxidants to diminish the adverse effects of postnatal glucocorticoid treatment on mortality and cardiac development.
Adler, A; Camm, EJ; Giussani, DA; Hansell, JA; Richter, HG, 2010
)
0.36
"We hypothesized that the adverse effects of postnatal glucocorticoid therapy are secondary to oxidative stress and that antioxidant treatment would diminish unwanted effects."( Investigation of the use of antioxidants to diminish the adverse effects of postnatal glucocorticoid treatment on mortality and cardiac development.
Adler, A; Camm, EJ; Giussani, DA; Hansell, JA; Richter, HG, 2010
)
0.36
"4-Hydroxynonenal (4HNE) is a toxic aldehyde which can accumulate during neurodegenerative diseases, such as AD."( Overexpression of aldehyde dehydrogenase-2 attenuates neurotoxicity induced by 4-hydroxynonenal in cultured primary hippocampal neurons.
Bai, J; Mei, Y, 2011
)
0.37
" A transgenic mammalian cell model was developed in which AKR7A2 was overexpressed in V79-4 cells and used to evaluate the ability of AKR7A2 to provide resistance against toxic aldehydes."( Human aldo-keto reductase AKR7A2 protects against the cytotoxicity and mutagenicity of reactive aldehydes and lowers intracellular reactive oxygen species in hamster V79-4 cells.
Ellis, EM; Ferrari, M; Li, D, 2012
)
0.38
" (MO) extracts and its curative role in acetaminophen (APAP)-induced toxic liver injury in rats caused by oxidative damage."( Moringa oleifera hydroethanolic extracts effectively alleviate acetaminophen-induced hepatotoxicity in experimental rats through their antioxidant nature.
Arulselvan, P; Fakurazi, S; Sharifudin, SA, 2012
)
0.38
" Prior work has shown that the efficiency of the GSH-dependent renal detoxification of haloalkene derived mercapturates is significantly decreased upon their deacetylation because of rapid transformation of the deacetylated products into toxic compounds mediated by β-lyase."( Inhibition of aminoacylase 3 protects rat brain cortex neuronal cells from the toxicity of 4-hydroxy-2-nonenal mercapturate and 4-hydroxy-2-nonenal.
Abuladze, N; Bragin, A; Cascio, D; Damoiseaux, R; Faull, K; Pushkin, A; Schibler, MJ; Tsirulnikov, K, 2012
)
0.6
"To investigate the role of human aldo-keto reductase 1A1 (AKR1A1) in the resistance to oxidative stress and the metabolism of toxic aldehyde in astrocytoma cells."( [Effect of AKR1A1 knock-down on H2;O2; and 4-hydroxynonenal-induced cytotoxicity in human 1321N1 astrocytoma cells].
Li, D; Liu, R; Zhang, Q; Zhou, L, 2013
)
0.39
" In conclusion, our present data suggests that HNE is highly toxic to serum-starved ARPE-19 cells but quercetin is able to reverse these adverse effects even when administered after an oxidative insult."( Quercetin alleviates 4-hydroxynonenal-induced cytotoxicity and inflammation in ARPE-19 cells.
Honkakoski, P; Hytti, M; Kaarniranta, K; Kauppinen, A; Piippo, N; Salminen, A, 2015
)
0.42
"Glutathione-S-Transferases (GSTs) have primarily been thought to be xenobiotic metabolizing enzymes that protect cells from toxic drugs and environmental electrophiles."( Regulatory roles of glutathione-S-transferases and 4-hydroxynonenal in stress-mediated signaling and toxicity.
Awasthi, S; Awasthi, YC; Chaudhary, P; Ramana, KV; Srivastava, SK, 2017
)
0.46

Compound-Compound Interactions

ExcerptReferenceRelevance
" The crystal structures of GSTA4-4 and an engineered variant of GSTA1-1 with high catalytic efficiency toward HNE, cocrystallized with a GSH-HNE conjugate analogue, demonstrate that GSTA4-4 undergoes no enantiospecific induced fit; instead, the active site residue Arg15 is ideally located to interact with the 4-hydroxyl group of either HNE enantiomer."( Substrate specificity combined with stereopromiscuity in glutathione transferase A4-4-dependent metabolism of 4-hydroxynonenal.
Atkins, WM; Balogh, LM; Kripps, KA; Le Trong, I; Mannervik, B; Shireman, LM; Stenkamp, RE; Zhang, W, 2010
)
0.36

Bioavailability

ExcerptReferenceRelevance
" It is hypothesized that altered NO bioavailability may result from an increase in endogenous NO synthase (NOS) inhibitors, asymmetric dimethly araginine (ADMA), and N(G)-monomethyl arginine, which are normally metabolized by dimethyarginine dimethylamine hydrolase (DDAH)."( Role of DDAH-1 in lipid peroxidation product-mediated inhibition of endothelial NO generation.
Cardounel, AJ; Chicoine, LG; Druhan, L; Forbes, SP; Guzman, JE; Lu, D; Murugesan, V; Parinandi, NL; Pope, AJ; Xia, Y, 2007
)
0.34
" The mechanism by which uric acid reduces the bioavailability of intrarenal nitric oxide is not known."( Role of oxidative stress in the renal abnormalities induced by experimental hyperuricemia.
Avila-Casado, C; Franco, M; Johnson, RJ; Nakagawa, T; Rodríguez-Iturbe, B; Sánchez-Lozada, LG; Sautin, YY; Soto, V; Tapia, E, 2008
)
0.35
" Because intestinal motility and permeability are also regulated through the bioavailability of serotonin (5-HT), we assessed markers of hepatic injury in serotonin reuptake transporter knockout (SERT(-/-)) and wild-type mice chronically exposed to different monosaccharide solutions (30% glucose or fructose solution) or water for 8 wk."( Serotonin reuptake transporter (SERT) plays a critical role in the onset of fructose-induced hepatic steatosis in mice.
Bergheim, I; Bischoff, SC; Brune, T; Haub, S; Kanuri, G; Volynets, V, 2010
)
0.36
"Oxidative stress contributes to lipid peroxidation and decreases nitric oxide (NO) bioavailability in atherosclerosis."( A fish-oil-rich diet reduces vascular oxidative stress in apoE(-/-) mice.
Andrisic, L; Cacabelos, D; Casós, K; Mitjavila, MT; Portero-Otín, M; Zaragozá, MC; Zarkovic, K; Zarkovic, N, 2010
)
0.36
" Reduced oxidative events with simultaneous increase in NO bioavailability may be involved in the insulin-sensitizing and cytoprotective effects of naringenin in fructose-fed rats."( Suppression of hepatic oxidative events and regulation of eNOS expression in the liver by naringenin in fructose-administered rats.
Anuradha, CV; Kannappan, S; Palanisamy, N, 2010
)
0.36
" Circulating adiponectin was independently associated with nitric oxide bioavailability and O2(-) production/eNOS uncoupling in both arteries and veins."( Interactions between vascular wall and perivascular adipose tissue reveal novel roles for adiponectin in the regulation of endothelial nitric oxide synthase function in human vessels.
Antoniades, C; Antonopoulos, AS; Bakogiannis, C; Casadei, B; Channon, KM; Choudhury, RP; Coutinho, P; De Silva, R; Demosthenous, M; Digby, J; Jalilzadeh, S; Lee, R; Margaritis, M; Petrou, M; Reilly, S; Sayeed, R; Shirodaria, C; Stefanadis, C; Tousoulis, D, 2013
)
0.39
" One of the most attractive strategies is the use of nanovehicles, because loading drugs into nanosized structures enhances their stability and solubility, thus improving their bioavailability and their antitumoral effectiveness."( The inclusion complex of 4-hydroxynonenal with a polymeric derivative of β-cyclodextrin enhances the antitumoral efficacy of the aldehyde in several tumor cell lines and in a three-dimensional human melanoma model.
Barrera, G; Biasi, F; Bisazza, A; Cavalli, R; Ciamporcero, E; Daga, M; Dianzani, C; Ferruti, P; Grazia Bernengo, M; Husse, M; Minelli, R; Novelli, M; Osella-Abate, S; Pettazzoni, P; Pizzimenti, S; Ranucci, E; Toaldo, C, 2013
)
0.39
" Importantly, the reduced bioavailability of this aldehyde appears to confer positive downstream effects to its target proteins such that HSPA2 could be protected from damage by 4HNE."( Inhibition of arachidonate 15-lipoxygenase prevents 4-hydroxynonenal-induced protein damage in male germ cells.
Aitken, RJ; Bromfield, EG; Dun, MD; McLaughlin, EA; Mihalas, BP; Nixon, B; Walters, JL, 2017
)
0.46
"We sought to determine the preventive effects of curcumin and its highly bioavailable preparation on noise-induced hearing loss in a novel murine model of permanent hearing loss developed by repeated exposure to noise."( Preventive effect of curcumin and its highly bioavailable preparation on hearing loss induced by single or repeated exposure to noise: A comparative and mechanistic study.
Imaizumi, A; Ogita, K; Onaka, Y; Yamaguchi, T; Yoneyama, M, 2017
)
0.46
"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
"Decrease in the bioavailability of vasoactive nitric oxide (NO), derived from the endothelial nitric oxide synthase (NOS3), underlines vascular endothelial damage."( Failure in the compensatory mechanism in red blood cells due to sustained smoking during pregnancy.
Chakraborty, P; Dugmonits, KN; Hegyi, P; Hermesz, E; Hollandi, R; Horváth, P; Maléth, J; Németh, G; Végh, AG, 2019
)
0.51
" Notably, boosting 4-HNE clearance through pharmacological re-activation of mitochondrial aldehyde dehydrogenase 2 (ALDH2) using Alda-1 or its improved orally bioavailable derivative AD-9308 restores Dicer activity."( 4-Hydroxynonenal impairs miRNA maturation in heart failure via Dicer post-translational modification.
Albuquerque, RP; Alves, AN; Arantes, GM; Bartesaghi, S; Bechara, LRG; Bozi, LHM; Campolo, N; Campos, JC; Candido, DS; Chen, CH; Cunha-Neto, E; Durán, R; Ferreira, JCB; Ferreira, LRP; Jesus, ICG; Kiyuna, LA; Krum, B; Leyva, A; MacRae, IJ; Mastrogiovanni, M; Mochly-Rosen, D; Mori, MA; Radi, R; Ramalho, LS; Yang, W; Zambelli, VO, 2023
)
0.91

Dosage Studied

ExcerptRelevanceReference
" Interestingly, body weight of the lowest dosage group was significantly higher than that of the control group at termination of the experiment."( Acute toxicity of trans-4-hydroxy-2-nonenal in Fisher 344 rats [corrected].
Chung, FL; Nishikawa, A; Sodum, R, 1992
)
0.59
" There was a bell-shaped dose-response curve to the enhancing effects of HNE, depending on the incubation time being recorded after only short periods (< or = 5 min) of the exposure of the cells to HNE; this was not shown by structurally-related aldehydes, such as 2-nonenal and nonanal."( Effect of 4-hydroxynonenal on superoxide anion production from primed human neutrophils.
Dianzani, C; Fantozzi, R; Ferrara, C; Parrini, M, 1996
)
0.29
" They also received diets containing 100 or 500 ppm auraptene for 4 weeks in groups of "initiation" feeding, starting 1 week before the first dosing of AOM."( Citrus auraptene exerts dose-dependent chemopreventive activity in rat large bowel tumorigenesis: the inhibition correlates with suppression of cell proliferation and lipid peroxidation and with induction of phase II drug-metabolizing enzymes.
Hara, A; Kakumoto, M; Kawabata, K; Koshimizu, K; Kuki, W; Maeda, M; Murakami, A; Odashima, S; Ohigashi, H; Ota, T; Takahashi, Y; Tanaka, T; Yamane, T; Yonei, H, 1998
)
0.3
" Each compound was evaluated for cytotoxicity to construct dosing regimens in transfection studies."( Alpha,beta-unsaturated aldehydes increase glutathione S-transferase mRNA and protein: correlation with activation of the antioxidant response element.
Kroll, DJ; Luckey, SW; Petersen, DR; Tjalkens, RB, 1998
)
0.3
" Urinary iPF2a-III increased in a time- and dosage-dependent manner after dosing with alcohol, with the peak urinary iPF2a-III excretion correlating with the rise in blood alcohol."( Alcohol-induced generation of lipid peroxidation products in humans.
Barry, OP; Burke, A; FitzGerald, GA; Lawson, JA; Lucey, MR; Meagher, EA; Rokach, J, 1999
)
0.3
" Additional male mice were dosed as described above and their livers were excised at 24, 48 h, and 7 days after the final dose."( Tumorigenicity of chloral hydrate, trichloroacetic acid, trichloroethanol, malondialdehyde, 4-hydroxy-2-nonenal, crotonaldehyde, and acrolein in the B6C3F(1) neonatal mouse.
Bucci, TJ; Chou, MW; Fu, PP; Kadlubar, FF; Samokyszyn, VM; Von Tungeln, LS; Yi, P, 2002
)
0.53
" In this study, we evaluated the efficacy of edaravone, a newly synthesized free radical scavenger, in its clinical dosage on an experimental model of acute liver injury in rats."( A free radical scavenger, edaravone, attenuates steatosis and cell death via reducing inflammatory cytokine production in rat acute liver injury.
Ishii, H; Kameyama, K; Kitamura, K; Kurita, S; Nakamoto, N; Saito, H; Saito, Y; Tada, S, 2003
)
0.32
" Swiss-Webster mice were dosed with celecoxib and rofecoxib and challenged with CT in ligated small intestinal loops, and intestinal segments from mice deficient in COX-1 and COX-2 were challenged with CT."( Role of cyclooxygenase enzymes in a murine model of experimental cholera.
Boldogh, I; Gessell-Lee, DL; Olano, JP; Peterson, JW; Popov, VL, 2003
)
0.32
" Because 4-HNE rapidly disappears from culture media, a multiple dosing regime was also employed to approximate short-term steady state 4-HNE concentrations relevant to physiological oxidative stress."( 4-Hydroxynonenal inhibits cell proliferation and alters differentiation pathways in human fetal liver hematopoietic stem cells.
Gallagher, EP; Moneypenny, CG, 2005
)
0.33
" The mean pure tone audiometric threshold (PTA), tinnitus loudness, subjective disturbance level [visual analogue scale (VAS) determination], and the indirect ROS dosage 48 h before and after medical treatment were evaluated."( Antioxidant therapy in idiopathic tinnitus: preliminary outcomes.
Brescia, G; Marioni, G; Savastano, M, 2007
)
0.34
" Exposure to 4-HNE elicited an increase in GSH concentrations in the control and hGSTA4 cells, although the dose-response of GSH induction differed among the two cell types."( Transfection of HepG2 cells with hGSTA4 provides protection against 4-hydroxynonenal-mediated oxidative injury.
Gallagher, EP; Gardner, JL; Huisden, CM, 2007
)
0.34
" Dose-response inactivation by 4HNE (4-hydroxynonenal) of hBAT (human bile acid CoA:amino acid N-acyltransferase) and CKBB (cytosolic brain isoform of creatine kinase) is associated with site-specific modifications."( High-resolution mass spectrometry analysis of protein oxidations and resultant loss of function.
Barnes, S; Barrett, K; Eliuk, SM; Kim, H; Renfrow, MB; Shonsey, EM; Srivastava, OP; Stella, D, 2008
)
0.35
" A dose-response study suggested that PYC showed protective effects against acrolein toxicity by modulating oxidative stress and increasing GSH."( Protective effect of Pycnogenol in human neuroblastoma SH-SY5Y cells following acrolein-induced cytotoxicity.
Ansari, MA; Keller, JN; Scheff, SW, 2008
)
0.35
" We compare the properties of this mixed models approach with nonparametric method GSEA and parametric method PAGE using a simulation study, and illustrate its application with a diabetes data set and a dose-response data set."( An integrated approach for the analysis of biological pathways using mixed models.
Chen, X; Wang, L; Wolfinger, RD; Zhang, B, 2008
)
0.35
" Once-daily dosing with EGCG increased hepatotoxic response."( Hepatotoxicity of high oral dose (-)-epigallocatechin-3-gallate in mice.
Ju, J; Kennett, MJ; Lambert, JD; Reuhl, KR; Sang, S; Yang, CS, 2010
)
0.36
"At peak postnatal hyperbilirubinemia, j/j Gunn rat pups were dosed with sulfadimethoxine to induce bilirubin encephalopathy."( Lipid peroxidation is not the primary mechanism of bilirubin-induced neurologic dysfunction in jaundiced Gunn rat pups.
Daood, MJ; Hoyson, M; Watchko, JF, 2012
)
0.38
" Our results showed that cell injury (indicated by apoptosis ratio, caspase 3/7-like activity, and LDH release), oxidative stress (indicated by ROS production, 4-HNE, and MDA contents), NOX activity, and NOX expression (NOX2 and NOX4 isoforms) were dramatically increased in PC12 cells following H/R, which were attenuated in the presence of VB-1 at dosage of 10(-7) or 10(-6) M."( Protective effect of vitexin compound B-1 against hypoxia/reoxygenation-induced injury in differentiated PC12 cells via NADPH oxidase inhibition.
Jiang, JL; Li, TB; Lou, Z; Luo, XJ; Peng, J; Tan, B; Yang, J; Yang, ZB; Zhou, YJ, 2014
)
0.4
" The dose of 100 mg/kg showed a better dose-response to the protective effects."( Anthocyanins suppress the secretion of proinflammatory mediators and oxidative stress, and restore ion pump activities in demyelination.
Abdalla, FH; Aiello, G; Amaral, MG; Andrade, CM; Bohnert, C; Carvalho, FB; Duarte, MM; Gutierres, JM; Lopes, ST; Oliveira, SM; Palma, HE; Pippi, NL; Spanevello, RM; Vieira, JM; Zago, AM, 2015
)
0.42
" Damage was seen to have been reduced with curcumin in the 8OHdG and TUNEL reactions, especially in the forebrain and the midbrain, although the dosage applied did not significantly change TAS and TOS levels."( An Investigation of the Effects of Curcumin on the Changes in the Central Nervous System of Rats Exposed to Aroclor 1254 in the Prenatal Period.
Alcigir, ME; Dikmen, BY; Dogan, HO; Dogan, K; Isgoren, A; Vural, SA; Yilmaz, FM, 2018
)
0.48
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Drug Classes (2)

ClassDescription
4-hydroxynon-2-enalAn enal consisting of non-2-ene having an oxo group at the 1-position and a hydroxy group at the 4-position.
4-hydroxynonenalA monounsaturated fatty aldehyde that is nonanal that has undergone dehydrogenation to introduce a double bond at any position in the aliphatic chain and in which a hydrogen at position 4 has been replaced by a hydroxy 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]

Pathways (3)

PathwayProteinsCompounds
4-hydroxy-2-nonenal detoxification212
creatine-phosphate biosynthesis47
Relationship between glutathione and NADPH036

Protein Targets (3)

Potency Measurements

ProteinTaxonomyMeasurementAverage (µ)Min (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Microtubule-associated protein tauHomo sapiens (human)Potency5.01190.180013.557439.8107AID1468
vitamin D3 receptor isoform VDRAHomo sapiens (human)Potency44.66840.354828.065989.1251AID504847
[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)
Transient receptor potential cation channel subfamily A member 1Rattus norvegicus (Norway rat)EC50 (µMol)24.63330.06002.22238.4000AID385780; AID482146; AID482147
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Bioassays (38)

Assay IDTitleYearJournalArticle
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.
AID651635Viability Counterscreen for Primary qHTS for Inhibitors of ATXN expression
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.
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.
AID385785Activation of TRPA1 channel in rat dorsal root ganglion neurons assessed as increase in intracellular calcium level at 50 uM2007Proceedings of the National Academy of Sciences of the United States of America, Aug-14, Volume: 104, Issue:33
4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1.
AID386031Induction of paw lifting in TRPA1-deficient intraplantarly dosed Swiss mouse at 120 nmol/paw2007Proceedings of the National Academy of Sciences of the United States of America, Aug-14, Volume: 104, Issue:33
4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1.
AID385787Reversal of activation of TRPA1 channel in rat dorsal root ganglion neurons at 100 uM by calcium imaging in presence of ruthenium red2007Proceedings of the National Academy of Sciences of the United States of America, Aug-14, Volume: 104, Issue:33
4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1.
AID482146Agonist activity at rat TRPA1 channel expressed in HEK293 cells assessed as increase in intracellular calcium influx2010Journal of medicinal chemistry, Jul-22, Volume: 53, Issue:14
Transient receptor potential ankyrin 1 (TRPA1) channel as emerging target for novel analgesics and anti-inflammatory agents.
AID386012Reversal of activation of TRPA1 channel in rat dorsal root ganglion neurons at 100 uM by calcium imaging in presence of capsazepine2007Proceedings of the National Academy of Sciences of the United States of America, Aug-14, Volume: 104, Issue:33
4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1.
AID386020Induction of paw lifting in Swiss mouse2007Proceedings of the National Academy of Sciences of the United States of America, Aug-14, Volume: 104, Issue:33
4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1.
AID386037Induction of neurogenic inflammation in rat dorsal spinal cord assessed as substance P release for 20 mins2007Proceedings of the National Academy of Sciences of the United States of America, Aug-14, Volume: 104, Issue:33
4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1.
AID386011Reversal of activation of TRPA1 channel in rat dorsal root ganglion neurons at 100 uM by calcium imaging in presence of gentamycin2007Proceedings of the National Academy of Sciences of the United States of America, Aug-14, Volume: 104, Issue:33
4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1.
AID386025Reversal of induction of allodynia in Swiss mouse in presence of capsazepine2007Proceedings of the National Academy of Sciences of the United States of America, Aug-14, Volume: 104, Issue:33
4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1.
AID482147Agonist activity at TRPA1 channel in rat DRG neurons assessed as increase in intracellular calcium influx2010Journal of medicinal chemistry, Jul-22, Volume: 53, Issue:14
Transient receptor potential ankyrin 1 (TRPA1) channel as emerging target for novel analgesics and anti-inflammatory agents.
AID385784Activation of TRPA1 channel in rat dorsal root ganglion neurons assessed as increase in intracellular calcium level2007Proceedings of the National Academy of Sciences of the United States of America, Aug-14, Volume: 104, Issue:33
4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1.
AID386026Reversal of induction of allodynia in Swiss mouse in presence of camphor2007Proceedings of the National Academy of Sciences of the United States of America, Aug-14, Volume: 104, Issue:33
4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1.
AID386017Increase in plasma extravasation in intraplantar dosed rat hind paw2007Proceedings of the National Academy of Sciences of the United States of America, Aug-14, Volume: 104, Issue:33
4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1.
AID385786Activation of TRPA1 channel in rat dorsal root ganglion neurons assessed as increase in intracellular calcium level at 300 uM2007Proceedings of the National Academy of Sciences of the United States of America, Aug-14, Volume: 104, Issue:33
4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1.
AID386023Reversal of induction of paw lifting in Swiss mouse at 15 to 240 nmol/paw in presence gentamycin2007Proceedings of the National Academy of Sciences of the United States of America, Aug-14, Volume: 104, Issue:33
4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1.
AID385781Agonist activity at rat TRPA1 channel expressed in HEK293 cells assessed as increase in intracellular calcium2007Proceedings of the National Academy of Sciences of the United States of America, Aug-14, Volume: 104, Issue:33
4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1.
AID386024Induction of allodynia in Swiss mouse2007Proceedings of the National Academy of Sciences of the United States of America, Aug-14, Volume: 104, Issue:33
4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1.
AID385788Reversal of activation of TRPA1 channel in rat dorsal root ganglion neurons at 100 uM by calcium imaging in presence of camphor2007Proceedings of the National Academy of Sciences of the United States of America, Aug-14, Volume: 104, Issue:33
4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1.
AID386027Reversal of induction of allodynia in Swiss mouse in presence of gentamycin2007Proceedings of the National Academy of Sciences of the United States of America, Aug-14, Volume: 104, Issue:33
4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1.
AID385780Agonist activity at rat TRPA1 channel expressed in tetracycline induced HEK293 cells assessed as increase in intracellular calcium2007Proceedings of the National Academy of Sciences of the United States of America, Aug-14, Volume: 104, Issue:33
4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1.
AID386022Reversal of induction of paw lifting in Swiss mouse at 15 to 240 nmol/paw in presence camphor2007Proceedings of the National Academy of Sciences of the United States of America, Aug-14, Volume: 104, Issue:33
4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1.
AID385783Reversal of activation of human TRPA1 channel expressed in xenopus oocytes by two electrode voltage-clamp technique in presence of ruthenium red2007Proceedings of the National Academy of Sciences of the United States of America, Aug-14, Volume: 104, Issue:33
4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1.
AID386018Reversal of increase in plasma extravasation in intraplantar dosed rat hind paw in presence of SR-1403332007Proceedings of the National Academy of Sciences of the United States of America, Aug-14, Volume: 104, Issue:33
4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1.
AID385782Agonist activity at human TRPA1 channel expressed in xenopus oocytes assessed as membrane currents by two electrode voltage-clamp technique2007Proceedings of the National Academy of Sciences of the United States of America, Aug-14, Volume: 104, Issue:33
4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1.
AID386028Induction of paw licking in intraplantarly dosed Swiss mouse at 120 nmol/paw2007Proceedings of the National Academy of Sciences of the United States of America, Aug-14, Volume: 104, Issue:33
4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1.
AID386019Induction of paw licking in Swiss mouse2007Proceedings of the National Academy of Sciences of the United States of America, Aug-14, Volume: 104, Issue:33
4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1.
AID385776Induction of neurogenic inflammation in rat esophagus assessed as CGRP peptide release for 20 mins2007Proceedings of the National Academy of Sciences of the United States of America, Aug-14, Volume: 104, Issue:33
4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1.
AID386021Reversal of induction of paw lifting in Swiss mouse at 15 to 240 nmol/paw in presence of capsazepine2007Proceedings of the National Academy of Sciences of the United States of America, Aug-14, Volume: 104, Issue:33
4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1.
AID386029Induction of paw lifting in intraplantarly dosed Swiss mouse at 120 nmol/paw2007Proceedings of the National Academy of Sciences of the United States of America, Aug-14, Volume: 104, Issue:33
4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1.
AID385777Induction of neurogenic inflammation in rat dorsal spinal cord assessed as CGRP peptide release for 20 mins2007Proceedings of the National Academy of Sciences of the United States of America, Aug-14, Volume: 104, Issue:33
4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1.
AID386030Induction of paw licking in intraplantarly dosed TRPA1-deficient Swiss mouse at 120 nmol/paw2007Proceedings of the National Academy of Sciences of the United States of America, Aug-14, Volume: 104, Issue:33
4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1.
AID386038Induction of neurogenic inflammation in rat esophagus assessed as substance P release for 20 mins2007Proceedings of the National Academy of Sciences of the United States of America, Aug-14, Volume: 104, Issue:33
4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1.
AID1346640Rat TRPA1 (Transient Receptor Potential channels)2007The Journal of neuroscience : the official journal of the Society for Neuroscience, Oct-17, Volume: 27, Issue:42
An ion channel essential for sensing chemical damage.
AID1346640Rat TRPA1 (Transient Receptor Potential channels)2007Proceedings of the National Academy of Sciences of the United States of America, Aug-14, Volume: 104, Issue:33
4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (2,941)

TimeframeStudies, This Drug (%)All Drugs %
pre-199075 (2.55)18.7374
1990's459 (15.61)18.2507
2000's1167 (39.68)29.6817
2010's1102 (37.47)24.3611
2020's138 (4.69)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 26.42

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 Index26.42 (24.57)
Research Supply Index8.03 (2.92)
Research Growth Index5.32 (4.65)
Search Engine Demand Index35.06 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (26.42)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials26 (0.86%)5.53%
Reviews208 (6.86%)6.00%
Case Studies8 (0.26%)4.05%
Observational3 (0.10%)0.25%
Other2,789 (91.92%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]