Sodium Demethylcantharidate has been found to be extremely effective at preventing the development of mouse hepatocytes, with an IC50 value of just 10 μM.

Cells are seeded in 96-well microtiter plates (1×104/wel/well; 100 μl), given time to equilibrate in quadruplicate wells, and then exposed to drugs for 72 hours (cisplatin, 1-5 and DMC: 2-200 μM; carboplatin, 50-3000 μM). Following that, MTT (5 mg/ml, 20 ml) in phosphate-buffered saline is added, and the cells are then incubated for 4 h at 37°C. After that, the MTT/medium is removed, the formazan product is dissolved in 150 ml of DMSO, and an absorbance measurement at 570 nm is made using a microtiter plate reader.

Absorption, Distribution and Excretion
May be absorbed through skin ...
Over 90% of radioactivity from (14)carbon labeled endothall administration orally to rats recovered in feces. Remainder recovered from urine and as expired air. Virtually complete recovery of administered dose within 48 hr.
When bluegills were exposed in aquaria to water containing 2 ppm of (14)Carbon endothall, less than 1% of the herbicide was absorbed by the fish. The concentration of (14)Carbon residues were highest in the viscera and lowest in the flesh. Endothall is also absorbed by the fish when fed through the digestive tract.
...labeled endothall /was administered/ to two lactating rats to determine whether endothall was secreted in milk The animals received a daily oral dose of 0.2 mg endothall (in 10% sucrose solution) for five consecutive days prior to delivery. After birth, dams received a daily dose of 0.4 mg endothall in 10% sucrose solution for five consecutive days. After sacrifice of the pups, no radioactivity was detected in any of the tissues or stomach contents suggesting that endothall was not secreted into the milk of lactating rats.
For more Absorption, Distribution and Excretion (Complete) data for ENDOTHALL (6 total), please visit the HSDB record page.

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Metabolism / Metabolites
The fate of the widely used herbicide, endothall, in various organisms and systems is reviewed. Limited results indicate that endothall absorbed by plants and fish is completely metabolized, but in mammals it is excreted largely as the bound form.

Interactions
The combined preparation of endothall and isopropyl phenylcarbamate, Murbetol, is hundreds of times more herbicidal than either of the ingredients alone.
Cell adhesion and neurite outgrowth, mediated by the neural cell adhesion molecule L1, are inhibited in a dose-dependent manner by ethanol and other small alcohols. Ethanol inhibition of L1-mediated adhesion may contribute to the development of fetal alcohol syndrome. Although the pharmacology of ethanol inhibition of L1 adhesion is well characterized and antagonist molecules have been identified, the cellular mechanism underlying this phenomenon is unclear. The identification of ethanol-sensitive and insensitive cell lines derived from the same stable transfection of L1 suggests that additional cellular factors regulate the ethanol effect. Here we investigate the role of intracellular signaling molecules in ethanol inhibition of L1 adhesion. L1-mediated functions can be controlled by phosphorylation events and several kinases are known to phosphorylate L1, including casein kinase II (CK2), ERK 1/2 and p90rsk. Pharmacological inhibition of CK2 activity blocked ethanol inhibition of L1 adhesion in ethanol-sensitive NIH/3T3 cells stably expressing human L1 (2A2-L1) and in BMP-7 treated NG108 cells. However, ethanol had no direct effect on CK2 activity or subunit localization. We next asked what effect protein phosphatase inhibitors would have on ethanol sensitivity. Pretreating 2A2-L1 cells and BMP-7 treated NG108 cells with okadaic acid significantly reduced ethanol inhibition of L1 adhesion in a dose dependent manner (IC50 = 10 nM). Similar effects were seen with another phosphatase inhibitor, endothall. Neither of these drugs had any effect on L1 adhesion in. the absence of ethanol. The necessity of CK2 and phosphatase activity for ethanol sensitivity may be explained by the fact that phosphatase PP2A is activated by CK2. Thus, inhibiting CK2 could also reduce PP2A activity. The fact that ethanol has no direct effect on CK2 activity supports the idea that another protein (PP2A), besides CK2, may be a more direct regulator of ethanol sensitivity for L1 adhesion. Together, these results show that ethanol' inhibition of L1 adhesion can be controlled by intracellular signaling pathways and suggest new avenues for the development of ethanol antagonists.
The beneficial effect of phosphodiesterase 5A inhibition in ischemia/reperfusion injury and cardiac hypertrophy is well established. Inhibition of the cardiac Na(+)/H(+) exchanger (NHE-1) exerts beneficial effects on these same conditions, and a possible link between these therapeutic strategies was suggested. Experiments were performed in isolated cat cardiomyocytes to gain insight into the intracellular pathway involved in the reduction of NHE-1 activity by phosphodiesterase 5A inhibition. NHE-1 activity was assessed by the rate of intracellular pH recovery from a sustained acidic load in the absence of bicarbonate. Phosphodiesterase 5A inhibition with sildenafil (1 umol/L) did not affect basal intracellular pH; yet, it did decrease proton efflux (J(H); in millimoles per liter per minute) after the acidic load (proton efflux: 6.97 +/- 0.43 in control versus 3.31+/- 0.58 with sildenafil; P<0.05). The blockade of both protein phosphatase 1 and 2A with 100 nmol/L of okadaic acid reverted the sildenafil effect (proton efflux: 6.77+/- 0.82). In contrast, selective inhibition of protein phosphatase 2A (1 nmol/L of okadaic acid or 100 umol/L of endothall) did not (3.86 +/- 1.0 and 2.61+/- 1.2), suggesting that only protein phosphatase 1 was involved in sildenafil-induced NHE-1 inhibition. Moreover, sildenafil prevented the acidosis-induced increase in NHE-1 phosphorylation without affecting activation of the extracellular signal-regulated kinase 1/2-p90(RSK) pathway. Our results suggest that phosphodiesterase 5A inhibition decreases NHE-1 activity, during intracellular pH recovery after an acidic load, by a protein phosphatase 1-dependent reduction in NHE-1 phosphorylation.

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Non-Human Toxicity Values
LD50 Rat oral 38-51 mg/kg for acid (technical)
LD50 Rat oral 182-197 mg/kg /Sodium salt (19.2% solution)/
LD50 Rat oral 206 mg/kg /Amine salt (66.7% formulation)/
LD50 Rat (male) oral 57 mg/kg
For more Non-Human Toxicity Values (Complete) data for ENDOTHALL (6 total), please visit the HSDB record page.

[1]. Anticancer Drugs. 2005 Sep;16(8):825-35.

The monohydrate is in the form of colorless crystals. Non corrosive. Used as a selective herbicide.
Endothal-disodium is an organic molecular entity.
A preparation of hog pancreatic enzymes standardized for lipase content.
See also: Pancrelipase (annotation moved to); Endothal-disodium (annotation moved to).

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Mechanism of Action
Cyclic AMP-dependent protein kinase (PKA) and Ca(2+)-calmodulin dependent protein kinase II (CaMKII)-mediated phosphorylation activate histamine synthesis in nerve endings, but the phosphatases deactivating it had not been studied. In this work we show that the protein phosphatase 2A (PP2A)/protein phosphatase 1 (PP1) inhibitor okadaic acid increases histamine synthesis up to twofold in rat cortical miniprisms containing histaminergic nerve endings. This effect was mimicked by the PP2A/PP1 inhibitor calyculin, but not by the inactive analog 1-norokadaone. Other phosphatase inhibitors like endothall (PP2A), cypermethrin and cyclosporin A (protein phosphatase 2B, PP2B) had much lower effects. The effects of okadaic acid appeared to be mediated by an activation of the histamine synthesizing enzyme, histidine decarboxylase. PKA-mediated activation of histamine synthesis decreased the EC(50) and maximal effects of okadaic acid. On the other hand, CaMKII-mediated activation of histamine synthesis decreased okadaic acid maximal effects, but it increased its EC(50). In conclusion, our results indicate that brain histamine synthesis is subjected to regulation by phosphatases PP2A and PP1, and perhaps also PP2B as well as by protein kinases.
... Protein phosphatase (PP) inhibitors and rat cerebellar glial cells in primary culture /were used/ to investigate the role of PP activity in the ability of glial cells to detoxify exogenously applied hydrogen peroxide (H2O2). The marine toxin okadaic acid (OKA), a potent PP1 and PP2A inhibitor, caused a concentration-dependent degeneration of astrocytes and increased the formation of hydroperoxide radicals significantly. Subtoxic exposures to OKA significantly potentiated toxicity by exogenous H2O2. The concentration of H2O2 that reduced by 50% the survival of astrocytes after 3 hr was estimated at 720+/-40 uM in the absence and 85+/-30 uM in the presence of the toxin. The PP inhibitors calyculin A and endothall also potentiated H2O2 toxicity in cerebellar astrocytes. OKA caused a time-dependent inhibition of both glial catalase and glutathione peroxidase, reducing by approximately 50% the activity of these enzymes after 3 hr, whereas other enzymatic activities remained unaffected. Also, OKA reduced the cellular content of total glutathione and elevated oxidized glutathione to about 25% of total glutathione. OKA-treated astrocytes cleared H2O2 from the incubation medium approximately two times more slowly than control cultures. Our results suggest a prominent role for PP activity in the antioxidant mechanisms protecting astrocytes against damage by H2O2.

C8H8NAO5-

207.13600

207.027

13114-29-9

Demethylcantharidate disodium;129-67-9

8519

Cyrstalline, white solid

Converted to anhydride at 90 °C
Colorless crystals. MP: 144 °C /Endothall monohydrate/

0

5

0

15

224

0

[O-]C(C1C(C([O-])=O)C2OC1CC2)=O.[NaH]

XRHVZWWRFMCBAZ-UHFFFAOYSA-L

InChI=1S/C8H10O5.2Na/c9-7(10)5-3-1-2-4(13-3)6(5)8(11)12;;/h3-6H,1-2H2,(H,9,10)(H,11,12);;/q;2*+1/p-2

disodium;7-oxabicyclo[2.2.1]heptane-2,3-dicarboxylate

Sodium Demethylcantharidate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O: ~50 mg/mL (~240.2 mM)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)