OKADAIC ACID

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C44H68O13
Molecular Weight	805.0029
Optical Activity	UNSPECIFIED
Defined Stereocenters	17 / 17
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C[C@@H](C[C@H](O)[C@H]1O[C@@H]2CC[C@@]3(CC[C@@H](O3)\C=C\[C@@H](C)[C@@H]4CC(C)=C[C@@]5(O[C@H](C[C@@](C)(O)C(O)=O)CC[C@H]5O)O4)O[C@H]2[C@H](O)C1=C)[C@H]6O[C@@]7(CCCCO7)CC[C@H]6C

InChI

InChIKey=QNDVLZJODHBUFM-WFXQOWMNSA-N

InChI=1S/C44H68O13/c1-25-21-34(55-44(23-25)35(46)12-11-31(54-44)24-41(6,50)40(48)49)26(2)9-10-30-14-18-43(53-30)19-15-33-39(57-43)36(47)29(5)38(52-33)32(45)22-28(4)37-27(3)13-17-42(56-37)16-7-8-20-51-42/h9-10,23,26-28,30-39,45-47,50H,5,7-8,11-22,24H2,1-4,6H3,(H,48,49)/b10-9+/t26-,27-,28+,30+,31+,32+,33-,34+,35-,36-,37+,38+,39-,41-,42+,43-,44-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C44H68O13
Molecular Weight	805.0029
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	17 / 17
E/Z Centers	1
Optical Activity	UNSPECIFIED

Description
Sources: https://media.cellsignal.com/pdf/5934.pdf | https://www.ncbi.nlm.nih.gov/pubmed/11860357 | https://www.ncbi.nlm.nih.gov/pubmed/2562908

Okadaic acid (OA) is a naturally occurring polyether toxin that was originally derived from marine dinoflagellates, Prorocentrium spp.. It is a reversible, potent and selective inhibitor of two serine threonine protein phosphatases: PP2A-C (PP2A) which is inhibited completely at 1 nM and PP1 which is inhibited at higher concentrations (IC50= 10-15 nM). PP2B is much less sensitive to okadaic acid than PP1, while PP2C is not inhibited. This selectivity is the basis for an improved identification and quantification procedure for these enzymes. The hydrophobic backbone of okadaic acid enables it to enter cells where it stimulates intracellular protein phosphorylation. It mimics the effects of insulin, enhances transmitter release at neuromuscular junctions, causes vasodilation and is a very potent tumor promoter. Okadaic acid is an extremely useful tool for studying cellular processes that are regulated by phosphorylation. Okadaic Acid is an activator of PKC.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Serine/threonine protein phosphatase 2A, catalytic subunit, alpha isoform 10 Target ID: CHEMBL4703 Sources: https://media.cellsignal.com/pdf/5934.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/11860357 \| https://www.ncbi.nlm.nih.gov/pubmed/9846650 \| https://www.ncbi.nlm.nih.gov/pubmed/9117116 \| https://www.ncbi.nlm.nih.gov/pubmed/11266161 \| https://www.ncbi.nlm.nih.gov/pubmed/2171991	Inhibitor 8504		0.1 nM [IC50]
Protein phosphatase 1 1 Target ID: Protein phosphatase 1 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2562908 \| https://media.cellsignal.com/pdf/5934.pdf	Inhibitor 8504		126.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Cancer 609 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2562181	Primary		Basic research	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Differences in metabolism of the marine biotoxin okadaic acid by human and rat cytochrome P450 monooxygenases.	2016-08	26374342
A novel toxicogenomics-based approach to categorize (non-)genotoxic carcinogens.	2015-12	25270620
Okadaic acid is taken-up into the cells mediated by human hepatocytes transporter OATP1B3.	2015-09	26134461
PCB153, TCDD and estradiol compromise the benzo[a]pyrene-induced p53-response via FoxO3a.	2014-08-05	24954032
CYP3A4 activity reduces the cytotoxic effects of okadaic acid in HepaRG cells.	2014-08	24504163
Active elimination of the marine biotoxin okadaic acid by P-glycoprotein through an in vitro gastrointestinal barrier.	2014-03-03	24374049
Modulation of albumin-induced endoplasmic reticulum stress in renal proximal tubule cells by upregulation of mapk phosphatase-1.	2013-10-25	23994741
Role of the nuclear xenobiotic receptors CAR and PXR in induction of cytochromes P450 by non-dioxinlike polychlorinated biphenyls in cultured rat hepatocytes.	2013-10-01	23770461
The catalytic subunit of protein phosphatase 2A (PP2Ac) promotes DNA hypomethylation by suppressing the phosphorylated mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK)/phosphorylated ERK/DNMT1 protein pathway in T-cells from controls and systemic lupus erythematosus patients.	2013-07-26	23775084
The marine toxin okadaic acid induces alterations in the expression level of cancer-related genes in human neuronal cells.	2013-06	23561263
Selective inhibition of the NLRP3 inflammasome by targeting to promyelocytic leukemia protein in mouse and human.	2013-04-18	23430110
Comparative toxicological study of the novel protein phosphatase inhibitor 19-Epi-okadaic acid in primary cultures of rat cerebellar cells.	2013-04	23335626
Sirt1 inhibits the transcription factor CREB to regulate pituitary growth hormone synthesis.	2013-04	23292070
RhoGEF17, a Rho-specific guanine nucleotide exchange factor activated by phosphorylation via cyclic GMP-dependent kinase Iα.	2013-03	23195829
Study of cytoskeletal changes induced by okadaic acid in HL-7702 liver cells and development of a fluorimetric microplate assay for detecting diarrhetic shellfish poisoning.	2013-02	21544917
Activation of a tunicate (Ciona intestinalis) xenobiotic receptor orthologue by both natural toxins and synthetic toxicants.	2012-02	22206814
Alterations in metabolism-related genes induced in SHSY5Y cells by okadaic acid exposure.	2012	22788371
Microcystin congener- and concentration-dependent induction of murine neuron apoptosis and neurite degeneration.	2011-12	21934130
Okadaic acid and dinophysis toxin 2 have differential toxicological effects in hepatic cell lines inducing cell cycle arrest, at G0/G1 or G2/M with aberrant mitosis depending on the cell line.	2011-12	21512803
Neurotoxicity induced by okadaic acid in the human neuroblastoma SH-SY5Y line can be differentially prevented by α7 and β2* nicotinic stimulation.	2011-09	21715663
Defects of protein phosphatase 2A causes corticosteroid insensitivity in severe asthma.	2011	22205926
BIM-mediated AKT phosphorylation is a key modulator of arsenic trioxide-induced apoptosis in cisplatin-sensitive and -resistant ovarian cancer cells.	2011	21655183
Crotepoxide chemosensitizes tumor cells through inhibition of expression of proliferation, invasion, and angiogenic proteins linked to proinflammatory pathway.	2010-08-27	20576605
Implication of TAp73 in the p53-independent pathway of Puma induction and Puma-dependent apoptosis in primary cortical neurons.	2010-08	20477944
A novel bile acid-activated vitamin D receptor signaling in human hepatocytes.	2010-06	20371703
Comparison of gene expression profiles in BALB/c 3T3 transformed foci exposed to tumor promoting agents.	2010-03	19840844
CLA reduces breast cancer cell growth and invasion through ERalpha and PI3K/Akt pathways.	2010-01-05	19800873
Extracellular signal regulated kinase 5 mediates signals triggered by the novel tumor promoter palytoxin.	2009-12-01	19716839
A structural basis for the reduced toxicity of dinophysistoxin-2.	2009-11	19916524
Morphological and biochemical changes associated with apoptosis induced by okadaic acid in human amniotic FL cells.	2009-10	18937299
Proteomic analysis reveals multiple patterns of response in cells exposed to a toxin mixture.	2009-06	19397276
Bortezomib overcomes tumor necrosis factor-related apoptosis-inducing ligand resistance in hepatocellular carcinoma cells in part through the inhibition of the phosphatidylinositol 3-kinase/Akt pathway.	2009-04-24	19261616
Multiple signal transduction pathways in okadaic acid induced apoptosis in HeLa cells.	2009-02-04	19084044
Identification of tumor promotion marker genes for predicting tumor promoting potential of chemicals in BALB/c 3T3 cells.	2009-02	19000923
Modulation of receptor phosphorylation contributes to activation of peroxisome proliferator activated receptor alpha by dehydroepiandrosterone and other peroxisome proliferators.	2008-03	18079279
Phosphoprotein analysis for investigation of in vivo relationship between protein phosphatase inhibitory activities and acute hepatotoxicity of microcystin-LR.	2007-12	18000846
Immunosuppressive leflunomide metabolite (A77 1726) blocks TNF-dependent nuclear factor-kappa B activation and gene expression.	1999-02-15	9973483
Acute rise in the concentration of free cytoplasmic calcium leads to dephosphorylation of the microtubule-associated protein tau.	1997-05-16	9200503
Induction of cyclooxygenase-2 expression by peroxisome proliferators and non-tetradecanoylphorbol 12,13-myristate-type tumor promoters in immortalized mouse liver cells.	1997-02-07	9013627
Inhibition of the glucocorticoid receptor expression by diverse tumor promoters in SENCAR mouse epidermis.	1997-02	21533367
Effect of okadaic acid on elastin gene expression in interstitial lung fibroblasts.	1996-12	8997264
Multifactor regulation of prostaglandin H synthase-2 in murine keratinocytes.	1996-12	8989914
Effect of diverse tumor promoters on the expression of gap-junctional proteins connexin (Cx)26, Cx31.1, and Cx43 in SENCAR mouse epidermis.	1996-03	8597533
Association of a 85-kDa serine kinase with activated fibroblast growth factor receptor-4.	1996-01-19	8576110
Tau phosphorylation in brain slices: pharmacological evidence for convergent effects of protein phosphatases on tau and mitogen-activated protein kinase.	1995-04	7723735
Multiple second messenger systems act sequentially to mediate rolipram-induced prolongation of prostaglandin E2-induced mechanical hyperalgesia in the rat.	1995-02	7715785
Signal transduction for nuclear factor-kappa B activation. Proposed location of antioxidant-inhibitable step.	1994-12-01	7963561
Antiapoptosis potential of bcl-2 oncogene by dephosphorylation.	1994-11-01	7654318
Induction of manganese superoxide dismutase mRNA by okadaic acid and protein synthesis inhibitors.	1994-07-01	8037686
Phosphorylation of the RNA polymerase II largest subunit during heat shock and inhibition of transcription in HeLa cells.	1994-03	8126066

Patents

Sample Use Guides

In Vivo Use Guide

Rats: Okadaic acid (200 ng) was microinjected bilaterally into cerebral ventricle (from the bregma: posterior 0.5 mm, lateral ±1.5 mm and from skull surface 3.6 mm ventrally) in light of the rat brain in stereotaxic coordinates. For each side a volume of 5.0 l was injected over a period of 10 min (0.2 l/min) followed by an additional 10 min waiting time before the micro-injection needle was removed in order to permeate local tissue sufficiently.

Route of Administration: Other

In Vitro Use Guide

Mouse oocytes were transiently exposed in vitro to different dosages (0, 0.01, 0.1, or 1.0 ug/ml) of the PP1 and PP2A phosphatase inhibitor okadaic acid (OA) during meiosis I and oocytes were cytogenetically analyzed. Significant (p < 0.05) OA dose-response increases in the frequencies of metaphase I (MI) arrested oocytes, MI oocytes with 80 chromatids instead of the normal 20 tetrads, and anaphase I telophase I (AI-TI) oocytes with two groups of an unequal number of chromatids were found.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:57:14 GMT 2025` Edited by `admin` on `Mon Mar 31 18:57:14 GMT 2025`
Record UNII	1W21G5Q4N2
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

NSC-677083

Preferred Name

English

OKADAIC ACID

Common Name

English

35-DEMETHYL-DTX 1

Common Name

English

(.ALPHA.R,2S,5R,6R,8S)-.ALPHA.,5-DIHYDROXY-.ALPHA.,10-DIMETHYL-8-((1R,2E)-1-METHYL-3-((2R,4'AR,5R,6'S,8'R,8'AS)-OCTAHYDRO-8'-HYDROXY-6'-((1S,3S)-1-HYDROXY-3-((2S,3R,6S)-3-METHYL-1,7-DIOXASPIRO(5.5)UNDEC-2-YL)BUTYL)-7'-METHYLENESPIRO(FURAN-2(3H),2'(3'H)-P

Systematic Name

English

1,7-DIOXASPIRO(5.5)UNDEC-10-ENE-2-PROPANOIC ACID, .ALPHA.,5-DIHYDROXY-.ALPHA.,10-DIMETHYL-8-((1R,2E)-1-METHYL-3-((2R,4'AR,5R,6'S,8'R,8'AS)-OCTAHYDRO-8'-HYDROXY-6'-((1S,3S)-1-HYDROXY-3-((2S,3R,6S)-3-METHYL-1,7-DIOXASPIRO(5.5)UNDEC-2-YL)BUTYL)-7'-METHYLENE

Systematic Name

English

ACANTHIFOLICIN, 9,10-DEEPITHIO-9,10-DIDEHYDRO-

Common Name

English

35-DEMETHYLDINOPHYSISTOXIN 1

Common Name

English

(2R)-3-((2S,6R,8S,11R)-2-((E,2R)-4-((2S,2'R,4R,4AS,6R,8AR)-4-HYDROXY-2-((1S,3S)-1-HYDROXY-3-((2S,3R,6S)-3-METHYL-1,7-DIOXASPIRO(5.5)UNDECAN-2-YL)BUTYL)-3-METHYLIDENESPIRO(4A,7,8,8A-TETRAHYDRO-4H-PYRANO(3,2-B)PYRAN-6,5'-OXOLANE)-2'-YL)BUT-3-EN-2-YL)-11-HY

Systematic Name

English

OKADAIC ACID [HSDB]

Common Name

English

OKADAIC ACID [MI]

Common Name

English

OA

Common Name

English

Classification Tree

Code System

Code

BAD BUG BOOK

OA

Code System Code Type Description

DRUG BANK

DB02169